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The Somatosensory System

Introduction

The somatosensory system comprises of ‘senses’ known as sensory modalities, these include; tactition (touch), temperature, proprioception (body position awareness) and nociception (pain). It is possible there are others, and these categories may be broken down further, for example kinaesthesia is the awareness of muscle strain/tension which is a form of nociception/proprioception.

Sensory receptors and sensory (afferent) neurones of the somatosensory system can be found from the periphery (such as the skin, muscles and organs) through to the deeper neurones of the central nervous system. Specific receptors are able to detect different stimuli; the stimulation of a receptor causes information to be sent along neurones to the corresponding area of the brain.

General Organisation of the Somatosensory System

A typical somatosensory pathway will begin with a sensory receptor (for example a mechanoreceptor which is able to detect stress/stretch in the skin – helping to form the tactile sensory modality). The stimulation of the receptor will cause information to be sent to the brain, where it will be perceived (in this example as touch). The information is sent to the brain through the spinal cord, typically three long neurones will facilitate this.

The cell body of the first neurone is located in the dorsal root ganglion of the corresponding spinal nerve. The second neuronal cell body is located in the midbrain for motor/touch sensory modalities and the spinal cord for pain sensory modalities. Neurones involved in pain sensory modalities travel to the thalamus, up the spinal cord via the spinothalamic tract.

It is at this point that the ascending neurones cross-over (decussate) to the opposite side of either the spinal cord or midbrain (depending on the sensory modality – above), typically upon entry of the structure of decussation. The axons of these neurones mainly terminate in the thalamus, but may also terminate in the reticular system or cerebellum of the brain.

In the case of touch and pain, the third neurone has its cell body located in the ventral posterior nucleus of the thalamus. The axon of this final neurone terminates in the postcentral gyrus (sometimes referred to as the somatosensory cortex) of the parietal lobe – where sensory information from different modalities is integrated.

Ascending Somatosensory Pathways

Information from sensory modalities is transmitted to the brain, via the spinal cord. These ascending neurones are able to take multiple pathways to reach their destination. These pathways can be split into three main routes.

Dorsal Column Pathway

The dorsal column pathway:

  • This pathway carries tactile and proprioception sensory modality information. Touch discrimination is owed to this pathway.
  • Sensory information arrives through the dorsal horn and is carried to the dorsal columns (which consist of the Gracile & Cuneate fasciculi)
  • The neurones synapse in the Gracile & Cuneate fasciculi of the medulla, where they decussate
  • The neurones terminate at the thalamus; they travel there along the medial lemniscus. The role of the medial lemniscus is simply to carry the neurones from the Gracile & Cuneate fasciculi of the medulla to the thalamus.

Ventrolateral Pathway

The ventrolateral pathway carries all sensory modalities (except proprioception) but is specifically involved in the propagation of pain. This pathway can be divided into two, as there are two possible tracts which the sensory modalities can take. These are the spinothalamic tract and the spinoreticular tract.

The Spinothalamic Tract

  • Nociceptors (pain receptors) detect a stimulus and neurones carry this to the spinal cord
  • These neurones head directly to the thalamus from the spinal cord, without synapsing elsewhere (via the medial lemniscus)
  • This pathway is associated with nociception such as that from thermal stimuli or from a pinprick

The Spinoreticular Tract

  • Follows the same pathway as the spinothalamic tract except the neurones synapse in the reticular formation of the medulla (primarily associated with the sleep/awake cycle)
  • From the reticular formation the neurones continue to the thalamus
  • This pathway is associated with ‘true pain’

Spinocerebellar Pathway

This pathway is associated with muscle and joint proprioceptors primarily, involving it in postural reflexes. Many neurones which travel via this pathway do not decussate, as is common in the other pathways.

After entering the spinal cord from an appropriate proprioceptor (or kinaesthesia receptor etc.), the neurones synapse in the dorsal horn and then head straight to the cerebellum.

Segmental Organisation

The spinal cord can be divided into sections by which part of the body it serves; cervical (head/ immediate upper body & arms), thoracic (trunk), lumbar (lower back/legs) and sacral (hind). Each of these sections is then made up of 5-12 nerve pairs each serving a smaller sub section of the body/skin; they send sensory information to the brain from their corresponding section.

  • Cervical Nerve Pairs – 8
  • Thoracic Nerve Pairs – 12
  • Lumbar Nerve Pairs – 5
  • Sacral Nerve Pairs – 5

This is significant diagnostically, because the deratomes (small section of skin served by a spinal nerve pair) are served by a specific spinal nerve pair. This means pain deriving from a deratome (or area of skin) if located, can be tracked back to its spinal nerve source.

For example, a human with pain in the skin of the abdomen (Thoracic nerve 12 [Th12]) could point out this pain to a doctor. The pain would be a symptom of possible damage to Th12 and further action could be taken.

Reflexes

Certain sensory modalities such as nociception provide information which needs to be responded to rapidly, using the example of nociception the information received may be that a hot object is causing tissue damage and requires the removal/release of the object quickly. This type of action is usually processed without involvement of the conscious brain and is known as a reflex.

Comparing a conscious response to reflex:

Conscious Response


Reflex Response


Reflexes offer the chance to act quickly by using local processing in the spinal cord – without the need for information to travel to the brain, thus saving time. However there is another type of reflex (sometimes called a long loop, compared to a simple reflex – short loop) called an inter-segmental reflex. This type of reflex looks more like a conscious response, yet the conscious brain is still not involved, so it is deemed a reflex. The processing is done in the brainstem or a separate spinal cord segment, the complete pathway is as follows:

An example of this type of reflex is the ‘Tonic-Neck’ reflex; the reorientation of the head (and thus neck) causes a reflex repositioning of the body and limbs to accommodate the new posture.

Receptors

So we have discussed the transmission of somatosensory signals, but what about their detection? As said earlier, receptors found all over the periphery of the body (e.g. skin, muscle, and organs) detect specific stimuli and transmit the information to the brain, but there are multiple types of receptors available to detect the different stimuli.

Mechanoreceptors

Two key attributes of a mechanoreceptor are the size of its receptive field and the speed at which its fibres adapt. The receptive field is important for discriminating from where a stimulus arises. A small receptive field has better discrimination than a larger one. Typically smooth skin has a small receptive field.

The speed at which fibres adapts concerns how quickly the receptors become desensitised to a stimulus. Rapidly adapting fibres will quickly become desensitised and stop generating action potentials to a stimulus (they may fire action potentials when the stimulus is stopped), whereas slow adapting fibres generally continue to fire action potentials during the length of exposure to the stimulus.

Meissner’s Corpuscle

Found in smooth skin, these mechanoreceptors have a small receptive field and rapidly adapting fibres. They are said to perceive fluttering stimuli.

Pacinian Corpuscle

Found deep within all types of skin, these mechanoreceptors have a large receptive field and rapidly adapting fibres. They are able to perceive vibrations.

Merkel Discs

Found in all types of skin, fairly shallow. These mechanoreceptors have small receptive fields and slow adapting fibres. They are able to perceive pressure.

Ruffini Corpuscle

Found deep within all types of skin, these mechanoreceptors have large receptive fields and slow adapting fibres. They are able to perceive stretching.

Free Nerve Ending

Common receptors for temperature and nociception, they are able to express different types of receptors; mechanical, thermal nociception and polymodal nociception (slow burning pain from chemicals, temperature etc.)

Stimulation of Receptors

The majority of somatosensory receptors are modified ion channels, which when stimulated allow the influx of ions and depolarisation which results in the generation of an action potential and its transduction.

Mechanoreceptors like those listed above; require some sort of mechanical stress e.g. stretching, to stimulate them. This causes the shape of the receptor to distort and opens the ion channel.

Chemoreceptors and thermoreceptors are stimulated by their corresponding stimulus, either directly or by the binding of the (chemical) stimulus to the receptor or a protein linked to the receptor. Again, stimulation leads to depolarisation and action potential generation.

Speed of Signal Transmission

The different receptors propagate their signals along nerve fibres which differ in the speed at which they transmit action potentials. Nerve fibres associated with pain are often much slower than those associated with touch. The different nerve fibres are classified as:

  • Aα – The fastest nerve fibre (72-120ms-1)
  • Aβ – Fast (36-72ms-1)
  • Aδ – Small, slow, myelinated fibres associated with nociception and temperature (4-36ms-1)
  • C – Small, very slow, unmyelinated fibres associated with nociception (0.4-2.0ms-1)

Pain

Pain Perception

Pain is the perception of nociception, until ‘pain’ reaches the cortex it is not pain, but nociception. It is believed that there is a ‘pain gate’ in the dorsal horn, the theory is that by preventing a ‘pain’ stimulus from passing through this gate you can prevent its perception as pain – making it a target for drugs.

Triple Response

The triple response is a phenomenon which occurs after inflammation, it results in pain – caused by irritant chemicals released after physical injury/damage. The chemicals are released onto the skin and free nerve endings. This causes nociception information to be sent to the spinal cord for processing, but the chemicals are also able to spread to other local nerves causing the release of more chemicals and more nociception transduction to the spinal cord. The overall effect is the spreading of inflammation and pain to a larger area than was originally damaged.

The Route of the Somatosensory System through the Brain

Upon reaching the brain, the majority of somatosensory information travels through the thalamus and continues further into the brain. From the thalamus, information head to the sensory cortex. Processing here allows the sensory modalities to be perceived.

The Vestibular System

Introduction

Located in the inner ear are several small organs responsible for balance. These organs belong to the vestibular system and give humans and many other mammals a sense of spatial awareness.

The vestibular apparatus lie within the vestibule, located in the inner ear labyrinth (along with the cochlea – involved in hearing). The major structures of the vestibular system are:

  • The otolithic organs; the utricle and the saccule – Involved in detecting linear (forward and back or up and down) motions.
  • The semicircular canals – Involved in detecting rotational movements

The Otolithic Organs

As mentioned above, the otolith organs comprise of the utricle and saccule, these are simply cavities which form part of the labyrinth of the inner ear. They contain hair cells and otoliths which send signals to the brain concerning the orientation of the head.

The hair cells of the utricle and saccule project into a gel like material. Within this gel lie many small calcareous structures – otoliths. Their function is to detect motion, which they do by movement. When the head is tilted the otoliths move and press onto the hairs protruding into the gel like substance. The hair cells are receptors which send sensory information to the brain, signalling the orientation of the head when stimulated by the otoliths.

The orientation of the utricle makes it sensitive to horizontal movement and acceleration (e.g. accelerating in a car) whilst the saccule is sensitive to vertical movement and acceleration (e.g. accelerating in an elevator).

The signals received from the sensory hairs can cause corrective motor movement of the posture or eyes, which helps to keep the animal balanced.

The Semicircular Canals

The semicircular canals of the inner ear are arranged over 3 spatial planes (x,y and z) to detect rotational movement across all 3 axis. At the base of all three canals lies a cluster of sensory hair cells (as found in the saccule and utricle). In a similar manner to the otolithic organs, the hair cells project into a gel, however the gel only forms a cap over the hairs – the rest of the canal is filled with fluid. The gelatinous cap is called a cupula.

Rotational movement causes the fluid in the semicircular canals to flow, this in turn pushes on the cupula which stimulates the hair cell receptors embedded within. The stimulation of the hair cells causes impulses to be sent to the brain by sensory neurones alerting the brain that the body is engaged in angular motion.

Sensory information from the vestibular system is detected by the vestibular nuclei via the vestibular nerve (one half of the vestibulocochlear nerve VIII).

Testing Cranial Nerves

Introduction

Cranial nerves arise from the brain directly (unlike spinal nerves which arise from the spinal cord). There are twelve pairs of cranial nerves, varying in length – from supplying nearby structures of the head to the Vagus nerve (X) which is the longest nerve in the body.

Cranial nerves may carry:

  • Sensory information only, i.e. information from an organ to the brain
  • Motor information only, i.e. information from the brain to an organ
  • Both sensory and motor information

Cranial nerves may also be either:

  • Afferent – Meaning to carry sensory information into the central nervous system
  • Efferent – Meaning to carry motor information away from the central nervous system
Cranial Nerve Type of Nerve Fibre Function
Olfactory (I) Sensory Carries sensory information from the olfactory bulb to the brain
Optic (II) Sensory Carries sensory information from the eye to the brain
Oculomotor  (III) Motor Enables the eye to make small, intricate movements
Trochlear (IV) Motor Supplies the extrinsic muscles of the eye
Trigeminal  (V) Both Receives sensory information from the face and supplies motor fibres involved in mastication
Abducens (VI) Motor Supplies the extrinsic muscles of the eye
Facial (VII) Both Supplies motor fibres for facial movements and receives sensory information from ‘anterior taste’
Vestibulocochlear (VIII) Sensory Carries sensory information from the vestibule (balance) and cochlear (hearing) of the inner ear
Glossopharyngeal (IX) Both Carries sensory information from posterior taste (posterior tongue and pharynx) and supplies muscle fibres of the pharynx
Vagus (X) Both Carries sensory information from the pharynx and larynx. Supplies muscle fibres of the larynx as well as; visceral motor fibres to the heart and various thoracic and abdominal organs (including the gastrointestinal tract)
Accessory (XI) Motor Supplies muscle fibres of the neck and shoulders
Hypoglossal (XII) Motor Supplies muscle fibres of the tongue

Testing Cranial Nerves

There are certain tests which can be done to ensure that a cranial nerve is working properly. The tests differ between the nerves due to their different functions. Each test usually has a reflex response which signifies that the cranial nerve is undamaged. The tests have been written primarily with animals in mind, but the majority of these are also observable in humans.

Cranial Nerve Test of Afferent Nerve Test of Efferent Nerve
Olfactory (I) A strong smell is used to test the aversion reflex. If the cranial nerve was undamaged the subject would respond to the smell
Optic (II) Avoiding creating air movement, a finger or hand is thrust towards the eye. If the optic nerve is undamaged, the subject will employ the menace reflex and close the eyelid in response to the finger/hand
Oculomotor (III) Testing eye muscles- Usually tested alongside nerves IV & VI, the movement of the eye and eyelid is observed in response to a stimulus. If this nerve is damaged, the pupils of the eye at rest point down & out

Pupillary reflex- Shining a light into the pupil of one eye should result in the constriction of both pupils

Trochlear (IV) Tested alongside nerve III & VI, if this nerve is damaged a strabismus (abnormal eye alignment) in an up & in direction will be apparent
Trigeminal (V) Touching the skin around the eye will result in the palpebral reflex (closing of the eyelids in response to the touching of the skin). If the nerve is damaged, this will not occur. Also, touching the cornea itself should result in the corneal reflex (closing of the eyelids in response to the touching of the cornea). Again this is absent if the nerve is damaged Should the efferent nerve become damaged, you will be able to observe a drooping jaw in the subject
Abducens (VI) Tested alongside nerve III & IV, if this nerve is damaged a strabismus in a medial, inward direction will be apparent
Facial (VII) The corneal reflex may be tested to check for damage to the nerve. In animals with motile pinna (external ear – not motile in humans), the handclap reflex can be tested. If the nerve is not damaged the pinna will move in response to a loud clap If the efferent nerve is damaged, drooping ears and facial paralysis may be observed. Ptosis (drooping of the eyelid) can also be observed. The menace and palpebral reflexes may be tested to check for nerve damage
Vestibulocochlear (VIII) Testing the Cochlea- The handclap reflex is tested. If the pinna do not respond, this may indicate damage to the nerve.

Testing vestibular responses- In response to altering the orientation of an animal i.e. tilting the body down to face the floor slightly, the neck will self right the head so the head is facing forwards if the nerve is undamaged (tonic neck reflex). If the nerve is damaged, animals may tilt their head with the ear down on the side of lesion/damage. Further observations include nystagmus – spontaneous eye movement, moving slowly in a lateral direction and then returning with a quick eye movement. The direction of the slow movement indicates the side of the lesion/damage

Glossopharyngeal (IX) Bilateral damage to the nerve results in the loss of the gag reflex. Observations that this nerve is damaged include dysphagia – difficulty swallowing
Vagus (X) Similarly to nerve IX, lack of the gag reflex and observing dysphagia can indicate damage. Laryngeal paralysis can be observed with damage, this can cause loss of ability to speak/bark etc. and loud noises when inhaling. Other respiratory and cardiovascular anomalies may arise if damaged.
Accessory (XI)
Hypoglossal (XII) If the nerve is damaged, minor dysphagia and a drooping tongue may be observed – often drooping to the side of damage/lesion if damage is unilateral

Synapses

Introduction

When an axon ends, the action potential which it carries can no longer be transmitted by the same medium. Axons end in a structure known as a synapse, the synapse allows the action potential to be propagated by means of chemicals (as opposed to electrically charged ions). An axon which terminates on an individual muscle fibre is known as a neuromuscular junction.

The terminating end of the axon has a bulbous structure, known as the presynaptic bulb. Within this bulb there can be one of many types of chemicals known as neurotransmitters. These neurotransmitters are the chemicals which transmit the action potential across the synapse (the space between the presynaptic bulb and the post synaptic structure is known as the synaptic cleft).

The most commonly found chemical used as a neurotransmitter is acetylcholine; however others include adrenaline, serotonin and dopamine. These neurotransmitters are housed in the presynaptic bulb contained in vesicles.

The process of transmission is as follows:

  • An action potential propagated to the presynaptic bulb (caused by an earlier stimulus)
  • The action potential depolarises the plasma membrane, this opens voltage gated channels in the membrane that allow the influx of Ca2+
  • The influx of Ca2+ results in some of the neurotransmitter containing vesicles to fuse with the presynaptic bulb membrane, resulting in the expulsion of the neurotransmitter into the synaptic cleft
  • The neurotransmitter diffuses across the synaptic cleft and binds to neurotransmitter specific receptors on the postsynaptic bulb
  • These receptors are ligand-gated ion channels and once the ligand (neurotransmitter) binds to the receptor, it opens allowing Na+ and K+ to diffuse through the channel
  • The influx of Na+ and efflux of K+ ions generates an action potential in the postsynaptic bulb which is propagated further
  • The neurotransmitter is released from the receptor causing it to close
  • The neurotransmitter is recycled, initially being broken down by an enzyme in the synaptic cleft (e.g. acetycholinesterase breaks down acetylcholine into acetate and choline)
  • Some of the neurotransmitter is taken up again by the presynaptic bulb (e.g. choline is pumped back into the presynaptic bulb by a choline carrier)
  • Enzymes convert the molecule back into a neurotransmitter (e.g. choline converted into acetylcholine) and the neurotransmitter is repackaged in an empty vesicle

It is possible for the neurotransmitter to be inhibitory as well i.e. prevent the generation of an action potential, e.g. glutamate is the primary excitatory neurotransmitter of the brain whereas GABA is the brain’s primary inhibitory neurotransmitter.

Types of Post Synaptic Receptors

As mentioned in the typical transmission above, neurotransmitters bind to a post synaptic receptor to result in either the inhibition or generation of an action potential. However, there are other types of post synaptic receptors which do not bind the neurotransmitter directly. The main 3 types are given below:

  • Ligand-Gated Ion Channels: (Fast – 0.1ms delay) also known as ionotropic receptors, these are the type of postsynaptic receptors spoken about earlier. They require the binding of a specific neurotransmitter, the binding of this neurotransmitter results in a conformational change causing the channel to open and allow the passage of ions. They are associated primarily with excitatory neurotransmitters such as acetylcholine and glutamate.
  • Metabotropic Receptors: (Slow – 10ms delay) unlike ionotropic receptors, these receptors are not directly associated with an ion channel. Instead they indirectly link with ion channels by means of signal transduction mechanisms, often G-proteins. Neurotransmitters will bind to the metabotropic receptor, resulting in the activation of these secondary messenger signal transduction mechanisms. The result is the opening of an ion channel and from this point, the process continues as in an ionotropic receptor.
  • Electrical Synapses: (Very Fast – <0.1ms delay) unlike either the ionotropic or metabotropic receptors, there is no association with an ion channel. Instead gap junction like channels pass directly through the presynaptic bulb and synaptic cleft heading directly into the postsynaptic bulb. This means the action potential can head straight through into the next axon without having to stop. This type of system is extremely fast and very uncommon. It is found in only a few specialised systems within the body.

Summation

The process of action potential propagation across synapses can vary. Most post synaptic terminals have a threshold which must be met in order for the action potential to be propagated. Therefore if a weak action potential arrives and is sub-threshold, the action potential ends there. It is not transmitted any further. There is an exception to this – summation.

A post synaptic structure such as a motor neurone may synapse with more than one presynaptic sensory neurone. If this is the case, then it is possible for summation to occur. Summation is when two sensory neurones fire simultaneous sub-threshold action potentials. Normally, as they are sub-threshold, they would not be propagated any further, but as there are two, the effect stacks in the process known as summation.

The above form of summation is known as spatial summation – the action potential of two neurones combine to allow threshold to be reached.

There is another form of summation however, temporal summation. Temporal summation is possible from just one sensory neurone. It works when a neurone is able to generate two action potentials in short succession. By the time the second action potential reaches the synapse, neurotransmitters from the previous action potential have not yet unbound from the postsynaptic receptors. This means the effects from both action potentials stack and threshold is reached.

Special Senses – Taste

Introduction

The tongue is the organ of taste. Perception of taste is also known as gustation and in a similar manner to smell it depends on chemoreceptors to detect specific chemicals from the environment. Specialised epithelial cells (Taste cells) detect these chemicals (tastants). In aquatic animals there is no distinction between olfaction and gustation. Insects use sensory hairs on their feet to taste. Taste probably evolved as a means for animals to detect whether what they were about to consume should be ingested or rejected.

In mammals, taste cells are clustered into taste buds which are scattered around the tongue and mouth. These taste buds are located very slightly beneath the surface of the tongue, a taste pore allows tastants to access the taste bud.

Taste buds are further localised onto raised clusters visible on the tongue, these are known as papillae. Differently shaped papillae are located at different sites on the tongue.

Taste Transduction

Mammals are able to detect the four conventional tastes (sweet, sour, bitter & salty) as well as ‘umami’, which is considered a savoury taste.

The sensory receptor cells (taste cells) which make up the taste buds contain smaller receptors in their plasma membranes. These receptors are specific to one of the above tastes.

When a tastant arrives at one of these receptors, it binds to it, resulting in a secondary messenger cascade. The receptor is coupled with a G-protein and the binding of a tastant activates the G-protein, beginning the secondary messenger process within the sensory receptor cell.

The G-protein eventually activates phospholipase C which in turn generates a secondary messenger known as IP3. IP3’s role in this secondary messenger system is to open IP3 gated calcium channels on the endoplasmic reticulum of the cell.

Opening of these channels causes Ca2+ to leave the endoplasmic reticulum and enter into the cytoplasm of the cell. Ca2+ also acts as a secondary messenger; it causes sodium channels to open allowing an influx of Na+ ions.

The sudden influx of Na+ ions causes the sensory receptor cell (taste cell) to depolarise, this depolarisation results in the local release of neurotransmitters (as taste cells do not have axons). This excites local sensory neurones which generate action potentials in response.

The axons of these neurones bundle together to form part of the facial nerve (VII), the glossopharyngeal nerve (IX) or the vagus nerve (X). Which one depends on the origin of the axon, anterior taste is carried by the facial nerve (VII) and posterior taste is carried by the glossopharyngeal nerve (IX). The throat/ epiglottis are dealt with by the vagus nerve (X).

All three cranial nerves eventually reach the gustatory nucleus of the ‘nucleus of the solitary tract’ in the medulla. From here the information can be sent to one of three places, each of which solicits a different response:

  • The gustatory cortex (via the thalamus) – Here taste is integrated and perceived as a taste.
  • The brainstem – From here reflexes associated with taste may be activated e.g. salivation
  • The Limbic system (especially the hypothalamus) – Emotional responses to taste (e.g. pleasure) can be elicited from here.

Special Senses – Smell

Introduction

The sensation of smell is also referred to as olfaction. The sensory cells of olfaction are chemoreceptor neurones with a direct connection to the brain. The organ responsible for smell is the olfactory organ (‘nose’), also responsible for olfaction is the vomeronasal organ. Odour molecules, which stimulate the olfactory cells, can be either present in gases or dissolved in vapour droplets. Molecules present in gas are detected by the main olfactory organ, whilst those dissolved in liquid are detected by the vomeronasal organ.

The important structures of the olfactory organ are as follows:

  • An external pair of ‘nares’ (nostrils) which act as the entrance to the organ.
  • An internal pair of ‘nares’ located just before the nasopharynx.
  • A richly vascularised anterior nasal mucosa, involved in heat exchange.
  • Turbinate bones, which refer to any of the spongy bones of the nasal passages. The turbinates divide the nasal airway into air passages, responsible for forcing inhaled air to flow in a steady, regular pattern around the largest possible surface of cilia and climate controlling tissue.
  • The sensory cells of the olfactory organ, the olfactory cells which are ciliated chemoreceptors.

Vomeronasal Organ

Located ventrally to the nose, this small organ is able to detect dissolved odours (e.g. pheromones) this makes it important for signalling related to sexual behaviour. The vomeronasal organ is present in many animals including humans and although functionality in animals has been shown there is still debate over whether such functionality is exhibited in humans.

Similarly to the olfaction organ, the vomeronasal organ contains receptors whose neurons possess axons which travel from the vomeronasal organ to the brain. The difference is that the neurons from the olfactory organ travel to the olfactory bulb of the brain whilst vomeronasal neurones travel to the accessory olfactory bulb.

Transduction Pathway of Signals

The pathway of transduction begins in the epithelial lining of the olfaction organ. Chemoreceptor neurones project from the epithelium into the mucosal layer of the organ. The projections are ciliated which increases the surface area of the receptors.

Lining the plasma membrane of the cilia are smaller receptors, these receptors are responsible for detecting individual odour molecules or odourants. The odour receptors are odorant specific, so different odours bind to different receptors. There are a few thousand, different odour receptors.

The odour receptors are G-protein coupled, so when an odour receptor binds its specific odourant the G-protein is activated and a secondary messenger cascade begins.

In the majority of these secondary messenger systems (a relay system where the activation of a receptor causes many changes in the cell, eventually leading to the desired outcome), the enzyme adenylyl cyclase is eventually activated. This enzyme converts ATP to cAMP. The production of cAMP opens Na+/Ca2+ permeable ion channels in the plasma membrane.

The influx of Na+/Ca2+ ions causes the chemoreceptor to depolarise. This causes the chemoreceptor to generate action potentials which are sent directly to the olfactory bulb of the brain.

The unmyelinated axons of the chemoreceptors bundle together in small groups, they then travel through the olfactory foramina, (Small holes in the cribriform plate [part of the skull which makes up the roof of the nasal cavity]) to the olfactory bulb.

These axons synapse with mitral cells in the olfactory bulb. From here the bundled axons from the mitral cells travel directly to the olfactory (piriform) cortex without first heading to the thalamus.

Here odours are processed; typically one smell is made from many different odourants. The different odourants are detected individually and eventually pieced back together to form the perceived, one smell.

Special Senses – Hearing

Introduction

The ear is the organ of hearing (and balance). Specially adapted receptor cells located in the inner ear are able to react to sound waves. The ear can be divided into three main parts, these are:

  • External ear
  • Middle ear
  • Inner ear

The external ear can be further broken down into:

  • The pinna – This is the funnel shaped cartilage on the external surface of the ear, it helps to guide sound waves into the ear drum. It leads directly to the external auditory canal/ external auditory meatus.
  • The external auditory meatus – Acts as a canal for the sound waves, carrying them to the tympanic membrane (ear drum).

The middle ear can be further broken down into:

  • The tympanic cavity – An air filled cavity, lined with a ciliated columnar mucous membrane which opens out into the Eustachian tube.
  • The tympanic membrane – Commonly known as the ear drum, they provide a boundary between the external and middle ear. The membrane is thin which allows it to convey sound waves (vibrations) to the auditory ossicles.
  • The auditory ossicles – These are the three small, flexible bones in the middle ear which are responsible for transmitting sound waves to the inner ear. The individual bones are named below (including common names):
    • Malleus (hammer)
    • Incus (anvil)
    • Stapes (stirrup)

The inner ear can be further broken down into:

  • The bony labyrinth – Consisting of the bony cochlea, bony vestibule and the bony semicircular canals. They contain perilymph which flows around the outside of the membranous labyrinth.
    • Oval Window – A thin membrane which links the bony labyrinth to the middle ear, the stapes transmits vibrations to the oval window, these vibrations are carried to the cochlea.
    • Round Window – Allows the release of pressure formed by sound waves transmitted to the cochlea by the oval window. Also dissipates sound waves, to prevent the prolonged sensation of a sound due to sound waves reverberating in the ear.
    • The membranous labyrinth – A system of interlinking tubes, containing endolymph. Specialised sensory receptors designed to respond to sound waves lie within. The  membranous labyrinth also consists of three parts:
      • Membranous cochlea – A spiral shaped tube filled with endolymph that contains sensory receptor cells which detect sound. At the end of each receptor is a sensory hair, the nerve fibres from these hairs go on to contribute towards the vestibulocochlear nerve (VII).
      • Membranous vestibule – Connects with the cochlea and semicircular canals, it contains specialised sensory receptors involved in balance when still.
      • Membranous semicircular canals – Three endolymph filled canals containing sensory receptors involved in balance when moving.

The Cochlea

The cochlea (the spiral, snail shaped structure of the inner ear) is responsible for detecting sound and allowing it to be perceived with volume and frequency. The cochlea has two large perilymph filled canals, an upper and a lower canal, separated by a small endolymph filled cochlea duct which runs almost the entire length of the cochlea. The upper canal is known as the vestibular canal and the lower canal is known as the tympanic canal.

The floor of the endolymph filled cochlea duct (basilar membrane) houses the organ of Corti. This organ contains hair cells which project into the cochlea duct. The hair cells act as mechanoreceptors and detect sound wave vibrations. The hairs are able to do this because sound waves entering the cochlea cause the basilar membrane of the cochlea duct to vibrate. As a result, the hairs bend and because they are mechanoreceptors, they are able to initiate action potentials by depolarisation.

Each hair cell contains a bundle of ‘hairs’ which project from its surface. Vibration of the basilar membrane moves the hairs, causing them to bend against the surrounding fluid and the tectorial membrane. The tectorial membrane is a membrane which lies just above the hairs of the hair cell and remains fixed in that position.

The process of perceiving sound is as follows; sound waves which have entered the ear eventually reach the stapes. The stapes vibrates on the oval window which produces a pressure wave in the perilymph of the upper vestibular canal. This pressure wave travels along the vestibular canal to the ‘apex’ (tip) of the cochlea duct. The cochlea duct ends just before the apex, allowing the pressure wave to travel back the way it came to the round window except by means of the tympanic (lower) canal. The energy of these pressure waves causes the basilar membrane of the cochlea duct to vibrate, stimulating the hair cells.

Species Difference

  • Fish & Other Aquatic Animals
    • Fish have no outer ears, only inner ears with no direct fluid connection to their environment. This is due to the easier detection of sound pressure waves in a water environment.
    • Instead, fish have neuromast receptors running along their lateral lines each of which is composed of a group of hair cells. The hairs are surrounded by a protruding jelly-like cupula.
    • The hair cells in the lateral line are similar to the hair cells inside the vertebrate inner ear, suggesting that the lateral line and the inner ear share a common origin.
    • Amphibians/ Reptiles
      • Amphibians/ reptiles have a more familiar hearing system when compared to mammals, although again they have no outer ear they do have the middle and inner ear.
      • They have an exposed tympanic membrane, from here the pathway continues very similar to mammals, via the small bones into fluid filled channels in the inner ear.

Perception of Frequency

The ear is able to distinguish between different frequencies of sound. Similar to wavelengths of electromagnetic scale (e.g. visible light), sound waves also have different variations in frequencies. In terms of audible sounds, the lowest (infra) sound detectable is 10Hz (1Hz being one vibration a second). This is an infrasound meaning it is not detectable by humans. Elephants however are able to hear sounds at this very low frequency. On the opposite end of the scale (ultrasound), bats are able to hear sounds with as high a frequency as 100kHz. To put things in to perspective, a humans hearing range is 20Hz – 20kHz.

The ear is able to detect these different frequencies due to an adaptation by the cochlea. The basilar membrane of the cochlea duct varies in stiffness and thickness. The result is that different frequencies of pressure waves cause different parts of the basilar membrane to vibrate; this therefore stimulates different hair cells. High pitch sounds (e.g. 18kHz) are detected near the stiff, thin base of the basilar membrane (near the oval window) and low pitch frequencies (e.g. 1kHz) are detected near the loose, thick end of the basilar membrane (near the apex of the cochlea duct).

Because of the way the basilar membrane vibrates, nerves which transmit the raw sound wave information to the brain each have their own characteristic frequency – the frequency at which they generate action potentials most frequently. These afferent nerves are located along the length of the cochlea – nerves located near the apex will have a characteristic frequency (the frequency at which action potentials are generated most readily) which is low (e.g. 1kHz) whereas nerves located near the oval window will have much higher characteristic frequencies.

There are two problems with this however. It is difficult for the basilar membrane to vibrate at very low frequencies e.g. 10Hz, if the basilar membrane is not vibrating then the hairs do not detect movement and the nerves are not stimulated – no sound. On the opposite end of the scale, very high frequencies cause vibrations so fast the neurones are not able to generate action potentials fast enough to keep up.

A process called phase-locking helps to detect the lower frequencies. This is where groups of neurones instead of generating action potentials as normal, they generate them at the frequency of the sound wave. For example, a 60Hz sound wave will cause a group of neurones to fire 60 times in a second.

At higher frequencies, when the nerves simply cannot fire fast to phase lock (e.g. 100kHz) the brain is able to simply detect that the very thinnest part of the basilar membrane is vibrating and interpret this as a sound. This is known as tonotopy.

Perception of Volume

Volume is also determined by the hair cell mechanoreceptors. In terms of waves, a louder sound has greater amplitude (height) but the same frequency (cycles per second). This is mimicked along the basilar membrane of the cochlea, louder sounds cause greater vibration of the membrane – making it rise and fall with greater height.

The greater displacement of the membrane causes the hairs of the hair cells to brush against the tectorial membrane more vigorously. This generates more action potentials in the sensory neurones as the brain perceives a louder sound.

Transduction of Sound Wave Signals

As you know, sound waves are ultimately detected by the hairs of the mechanoreceptor hair cells. The bending of the hairs must be converted into the generation of action potentials by sensory neurones which synapse with the hair cells before the information can be processed in the brain.

When a sound wave causes a certain part of the basilar membrane to vibrate (location depending on its frequency) the hairs bend against the tectorial membrane. As they bend mechanoreceptors cause ion channels in the hair cells to open/close depending on which direction they bend.

The initial direction of bending (stimulus applied) opens the ion channels causing an influx of ions and depolarisation of the mechanoreceptor. The depolarisation causes an increase in the amount of neurotransmitter released across the synapse with sensory neurone. This in turn increases the frequency at which the sensory neurones generate action potentials.

As the hairs bend the other way (stimulus removed), the ion channels close. The closure of the ion channels causes the hair cell to hyperpolarise. This reduces the amount of neurotransmitter released by the cell and the synapsing sensory neurone reduces the frequency at which action potentials are generated.

Auditory Pathway

The auditory pathway shows how sound waves are eventually processed by the brain. So far we have discussed from the sound entering the cochlea (via the external auditory canal) to hair cells of the organ of Corti.

From the hair cells, the majority of information travels along large, fast, myelinated nerves. The axons of these nerves join together and form the auditory nerve (part of the vestibulocochlear nerve [VII]).

The auditory nerve initially travels through the cochlear nuclei; one nucleus located both dorsally and laterally. Information from either ear remains separate at this stage.

The lateral lemniscus is a tract of axons in the brainstem that carries information about sound from the cochlear nucleus to various brainstem nuclei and ultimately the inferior/caudal colliculus of the midbrain.

The inferior colliculus is the principal midbrain nucleus of the auditory pathway and receives input from several more peripheral brainstem nuclei in the auditory pathway, as well as inputs from the auditory cortex. It is here that sound location data from different areas becomes integrated, allowing sound direction/ distance to be interpreted.

Two ways in which sound location is distinguished include:

  • Time delay – If a sound arrives at one ear first, this is recognised in the inferior colliculus.
  • Volume Differences – Subtle differences in the volume of a sound at each ear also help to place a sound.

The Medial Geniculate Nucleus is part of the auditory thalamus and is what finally connects the inferior colliculus to the auditory cortex. It is involved in the tonotopic organisation of sound information, as well as the detection of relative intensity and duration of a sound.

The primary auditory cortex is the region of the brain that is responsible for processing of auditory information. It is located on the temporal lobe, and performs the basics of hearing; pitch and volume.

The auditory cortex is involved in tasks such as identifying and segregating auditory “objects” and identifying the location of a sound in space.

Special Senses – Vision

Introduction

The eye is the organ of vision. The main cells responsible for beginning the process of converting light (of varying wavelengths) into an interpreted image we can ‘see’ are photoreceptors. These cells respond to the stimulus of light and are located in the innermost layer of the eye – the retina.

The eyeball itself can be split into three layers:

  1. The sclera – The protective, fibrous outer coating of the eye which also helps to maintain the eyeball’s globe shape. The sclera layer also includes the cornea, which helps to focus light onto the retina.
  2. The uvea – A vascular and pigmented layer consisting of the following:
    1. Choroid – Darkly pigmented to prevent light escaping the eye, it contains blood vessels which supply all the internal structures of the eyeball.
    2. Tapetum Lucidum – A triangular area containing light reflecting cells found behind the retina in some species (e.g. cats); it helps to reflect light back to the retina, especially useful in low light situations.
    3. Ciliary body – Contains the smooth ciliary muscles which control lens thickness and shape.
    4. Suspensory ligament – Supports the perimeter of the lens.
    5. Iris – Contains radial and circular smooth muscles which control the opening of the pupil to regulate the amount of light entering the eye and to prevent damage.
  3. The retina – The lens focuses light onto the photoreceptor cell of this innermost layer of the eye. The information which the photoreceptors receive is transmitted to the brain via the optic nerve (II). The image arrives at the photoreceptor cells inverted due to the way the lens focuses the light, however the brain processes the image so we see it the correct way up. The retina also consist of several layers:
    1. Pigmented layer – Prevents light leaking out from the eye, synergising with choroid of the uvea to produce a greater effect.
    2. Photoreceptors – There are two types of photoreceptors, both with different shapes and functions, these are:
      1. i.      Rods – Sensitive even in low light conditions but they only provide black and white vision. This makes them useful for night vision. High sensitivity, low acuity.
      2. ii.      Cones – Only sensitive in well light conditions, but they are able to provide colour vision. Low sensitivity, high acuity.
    3. Bipolar neurones – Receive the raw information from the rods and cones and transmit this to the ganglion cells. One neurone can serve multiple rods/cones.
    4. Horizontal/ Amacrine cells – Located between the rods/ cones and the ganglion cells, they are situated amongst the bipolar neurones. Their role is to integrate the visual information received from the rods/ cones before it is sent to the brain.
    5. Ganglion cells – Each bipolar neurone synapses with a ganglion cell. When an action potential is generated from rod/cones stimulation, it is transmitted down the axons of the ganglion cells.

Light enters the eye through the cornea, pupil and then lens. The lens focuses the image onto the retina. Photoreceptor cells of the retina are stimulated by the light sending nerve impulses from the rods/cones through bipolar neurones to the ganglion cells. The axons of the ganglion cells travel across the surface of the retina towards the optic disc at the centre of the retina. The nerves from all the ganglion cells bundle together at the optic disc to form the optic nerve (II). There are no rods or cones located on the optic disc. From the optic nerve (II) information is carried to the primary visual cortex of the cerebral hemispheres located at the rear of the brain. This is where the light information is finally interpreted as an image.

Species Differences

There are certain differences which are observed between different species, a few of these are listed below:

  1. Pecten – Birds contain an organ within their vitreous humour (the jelly-like substance which fills the eye cavity). It is thought that the pecten both nourishes the retina and controls the pH of the vitreous body. It is present in all birds and some reptiles.
  2. Shape – The actual shape of the eyeball itself may vary between species. For example humans have a globe shaped eyeball, whereas horses have a non-spherical, almost cuboidal eyeball. This allows for more than one fovea (the area of the retina which provides maximum acuity).
  3. Fovea – As above, the size, shape and number of fovea may differ between species.
  4. Pupils – The shape and size of pupils also differs between species. Humans have round pupils, whereas cats for example have pupils shaped as vertical slits.

Diseases of the Retina

There are a many diseases which can affect the retina. Some common examples found in animals are:

  • Collie eye anomaly (CEA) – a congenital, inherited, bilateral eye disease of dogs involving the retina, choroid, and sclera. It can be a mild disease or cause blindness. CEA is caused by a simple autosomal recessive gene defect. There is no treatment.
  • Progressive retinal atrophy (PRA) – a group of genetic diseases seen in certain breeds of dogs and more rarely, cats. It is characterised by the bilateral degeneration of the retina, causing progressive vision loss culminating in blindness. The condition in nearly all breeds is inherited as an autosomal recessive trait. PRA can be considered similar to retinitis pigmentosa in humans.
  • Retinopathy – a general term that refers to some form of non-inflammatory damage to the retina of the eye. Cats experience ‘Taurine Deficient Retinopathy,’ a lack of taurine in the diet of the cat leads to the degeneration of the photoreceptors. Cat food is therefore supplemented with taurine.

Photoreceptor Cells

As mention earlier, the photo receptor cells are rods and cones. Cones are associated with colour vision but are not sensitive in low light, whilst rods are – but they have low acuity and provide only black and white vision.

The initial steps for photoreceptors in perceiving light requires the use of a chemical called rhodopsin, found in rod cells it can be broken down into the protein opsin and a small molecule retinal (Derived from retinol – vitamin A). Rhodopsin is extremely sensitive to light, enabling vision in low-light conditions. When exposed to light, the pigment immediately photobleaches breaking down into opsin and retinal. The breakdown of rhodopsin causes a secondary messenger cascade (phototransduction) eventually resulting in the information reaching the visual cortex.

Similar to rod cells, cone cells contain a rhodopsin like pigment called iodopsin or photopsin. Just like rhodopsin, photopsin contains opsin and retinal except the opsin component varies slightly by a few amino acids. These slight changes allow them to absorb different wavelengths of light. In humans there are three extra opsins each tuned to different wavelengths:

  • Opsin S – Blue, wavelengths 400-500nm
  • Opsin M – Green, wavelengths 450-630nm
  • Opsin L – Red, wavelengths 500-700nm

The three colour photopsins work together in bright light, to give colour vision. Species which utilise:

  • Only one photopsin are called monochromats
  • Two – dichromats
  • Three – trichromats
  • Four – tetrachromats (Opsin R – its range overlaps with all the opsins)

In summary the differences between the two types of photoreceptor are:

  • Rods – Black & white (night) vision, high sensitivity, low acuity, uses rhodopsin = opsin + retinal
  • Cones – Colour vision, low sensitivity, high acuity, uses photopsin/iodopsin = retinal + opsin S (blue) OR opsin M (green) OR opsin L (red) (OR opsin R – Tetrachromats)

Phototransduction

Phototransduction covers the process of how the photoreceptors send information to the brain. The process is as follows:

  • Photoreceptors in the absence of light release the neurotransmitter glutamate. When light falls on the photoreceptors they stop releasing glutamate.
  • cGMP is bound to sodium channels in the plasma membrane of the rods. It keeps the sodium channels open and maintains a membrane potential of around -40mV
  • Opsin is a G-Coupled Protein Receptor which spans the membrane of discs located just inside of the rods.
  • When light reaches rhodopsin, it causes opsin to isomerise (change from a cis to trans shape).
  • The now active form of rhodopsin activates a G protein called transducin.
  • Transducin in turn activates the enzyme phosphodiesterase
  • The active enzyme phosphodiesterase hydrolyses cGMP to CMP, causing it to detach from the sodium channel, thus the sodium channel closes.
  • As sodium can no longer enter into the rod, the membrane potential decreases to -70mV causing the rod to hyperpolarise. Glutamate is no longer released.
  • Bipolar cells which synapse with the rods may generate an action potential when glutamate is no longer being released across the synaptic cleft.

Glutamate may act as either an excitatory or inhibitory molecule to the bipolar neurone which synapses with the rod. This gives rise to ‘on’ and ‘off’ bipolar cells.

The ‘on’ bipolar cells are activated by light – therefore glutamate was acting as an inhibitor as glutamates inhibition (caused by light hitting the rod) activates the bipolar cell.

The ‘off’ bipolar cells are deactivated by light – glutamate was therefore acting as an excitatory molecule. Light prevents glutamate being released which was stimulating the bipolar cell.

Receptive Fields and Lateral Inhibition

Ganglion cells only detect light from a region known as its receptive field. The receptive field is split into the field centre and the field surround. Basically forming two concentric circles, these circles representing regions at which light is detected.

Some ganglion cells will only generate action potentials when the centre field is lit. (On centre cells) Whilst the others only generate an action potential if the surround field is lit. (Off-centre cells)

With receptive fields alone, images would appear blurry. The process of lateral inhibition aids this process to form sharp images. Lateral inhibition is the ability of a neuron to reduce the activity of its neighbours. In terms of vision this means ganglion cells receiving a moderate or low amount of light (yet still enough to generate an action potential) which contribute to blurry images, can be inhibited by neighbouring neurons which are receiving greater light stimulus. The brain is able to perceive sharper images from this information.

It is believed the horizontal and amacrine cells discussed earlier are involved in this process. Horizontal cells being involved in sustained lateral inhibition and amacrine cells believed to be involved with transient lateral inhibition.

The Visual Pathway

As you know, light enters through the lens and is focused on the retina. From there it is detected by photoreceptor cells which synapse with bipolar cells. These bipolar cells synapse with ganglion cells. The axons of the ganglion cells group together at the centre of the retina to form the optic disc. This goes on to form the optic nerve (II).

From the optic nerve (II) the majority of axons are directed to the lateral geniculate nucleus (via the optic chiasm and the optic tract) in the thalamus. The lateral geniculate nucleus (LGN) acts as the primary processing centre for visual information received by the retina. The neurones of the LGN send their axons through the optic radiation to the primary visual cortex.

There is a visual cortex for each hemisphere of the brain, both located at the very back of the brain. The left hemisphere visual cortex receives signals from the right visual field and the right visual cortex from the left visual field. Within the visual cortex, groups of ‘simple cells’ (receptive areas) join to form ‘complex cells’ which are able to detect particular shapes.

From the visual cortex, information is sent to the cortex in the temporal lobe; here it is connected to a response i.e. recognising a face, performing a task etc.

Development of Vision

Studies have been conducted on animals to determine how they cope with monocular deprivation:

“It was confirmed that suturing the lids of one eye (monocular deprivation), until only 5 weeks of age, leaves virtually every neurone in the kitten’s visual cortex entirely dominated by the other eye. On the other hand, deprivation of both eyes causes no change in the normal ocular dominance of cortical neurones, most cells being clearly binocularly driven.

Kittens were monocularly deprived until various ages, from 5 to 14 weeks, at which time reverse suturing was performed: the initially deprived right eye was opened and the left eye closed for a further 9 weeks before recording from the visual cortex.

Reverse suturing at 5 weeks caused a complete switch in ocular dominance: every cell was dominated by the initially deprived right eye. Reverse suturing at 14 weeks, however, had almost no further effect on ocular dominance: most cells were still driven solely by the left eye. Animals reverse sutured at intermediate ages had cortical neurones strongly dominated by one eye or the other, and they were organized into clear columnar groups according to ocular dominance.

Thus, between 5 weeks and 4 months of age, there is a period of declining sensitivity to both the effects of an initial period of monocular deprivation and the reversal of those effects by reverse suturing.” Blakemore, C., Van Sluyters, R.C. Reversal of the physiological effects of monocular deprivation in kittens: Further evidence for a sensitive period (1974) Journal of Physiology, 237 (1), pp. 195-216.

As it states, this shows how important early development of the visual system is. Other experiments have also been conducted, where animals have been brought up in closed environments, which for example contain only vertical lines. After development, when the animal is released from this environment it is not able to process horizontal lines. It is therefore unable to perceive these lines.

Appetite Control & Maintaining Constant Body Weight

Introduction

The key point of regulating food intake is to maintain a constant body weight. Food intake (energy input) must therefore balance against factors resulting in a loss of body weight, energy output. Such factors as basal metabolic rate or physical activity (exercise). Because of the simple relationship between energy input and output, there are only three possible states of energy balance:

  1. Positive – Energy input is greater than energy output, body weight increases – excess energy is stored in adipose tissue as fat.
  2. Negative – Energy input is less than energy output, body weight decreases – energy stores (adipose/muscle tissue) converted into energy to meet demands.
  3. Neutral – Energy input is equal to energy output, body weight is unchanged.

It is natural for organisms to fluctuate between states of positive/ negative energy balance, e.g.:

  • Hibernation – Despite a decrease in metabolic rate (energy output), the animal is still not receiving any energy input as it i s not consuming food. The animal must therefore breakdown stores of energy from its own body reserves such as adipose tissue. The animal usually prepares for this state of negative energy balance by increasing energy input before hibernation to build up body reserves.
  • Pregnancy/ Lactation – Increased energy output required for producing milk or the development of offspring is usually met by the mother, who greatly increases energy input (food intake). Yet it is very easy to not meet these energy demands, which can result in a loss of weight in the mother. For example in sows the energy requirements to produce enough milk for a litter of 10 can be up to four times that of a non-pregnant sow, if the mother does not consume enough food (or is not given enough food) she will begin to use her own stores of energy and lose weight.

Hypothalamic Control of Appetite

The body is believed to have a predefined, set weight controlled by precise regulation of appetite. This can be observed in most animals who maintain a near constant weight even when food resources are plentiful. It is believed that the hypothalamus is responsible for this precise regulation of appetite. The hypothalamus is an important region of the brain which controls homeostasis, aids in the control of the autonomic nervous system and more importantly for this situation, acts as a link between the endocrine and nervous system.

The hypothalamus is able to detect hormones in the blood secreted by peripheral fat, the liver and the gut all of which reveal details about the current energy status of the body (positive, negative or neutral). It also receives signals from other parts of the brain, such as the brainstem (connecting the brain to the spinal cord and consisting of the midbrain, medulla oblongata and the pons). The brainstem transfers important information from the peripheral nervous system to the mid and forebrain. In terms of appetite control, the brainstem forms direct neuronal connections with the gut allowing it to regulate mechanical processes involved with appetite/ food consumption such as chewing and swallowing (The volume of consumption is controlled by the hypothalamus). Areas of the brain involved in sleep arousal and therefore being awake and reactive to stimuli are also important as they control food-seeking behaviour.

Hypothalamic Control of Appetite Behaviour

In simple terms, the sections of the hypothalamus responsible for appetite can be split into two – an ‘appetite centre’ and a ‘satiety centre’ (satiety meaning the feeling of being ‘full’). The appetite centre is responsible for causing the feeling of hunger, therefore initiating searching behaviour for food. The satiety centre therefore, causing the opposite and giving the feeling of ‘being full’ ceasing the desire to consume more food.

Test have been conducted on these ‘centres’ and the findings prove the theory – animals with removed/ damaged appetite centres no longer appear to feel hunger, refusing to eat and becoming anorexic. Animals with a removed/ damaged satiety centre, as expected no longer appear to feel ‘full’ continuing to eat and causing great increases in body weight.

There are two main theories behind appetite regulation – the ‘glucostat’ theory and the ‘lipostat’ theory. Both however show the hypothalamus in communication with the peripheral systems.

The Glucostat Theory

The glucostat theory regulates short-term control over appetite. The glucostat theory is believed to be responsible for the frequency and size of meals, preventing overeating during meals. During a meal, glucose metabolism is monitored by specialised receptor cells in the hypothalamus, when glucose levels rise to a certain threshold, neuronal activity within the satiety centre begins to increase. This removes the feeling of hunger and the animal finishes the meal. When glucose levels fall below the threshold, neuronal activity in the appetite centre will increase and the animal will go in search of its next meal. As you can see, this is a short-term control over appetite.

Interestingly, in ruminants the intravenous infusion of glucose (to prevent the glucose being fermented in the forestomach by symbiotic bacteria) does not affect satiety centre neuronal activity i.e. does not affect the ruminant’s appetite, as it would in other animals. Yet the infusion of volatile fatty acids (the product of fermentation by bacteria in the forestomach and the main source of energy for the ruminant) does affect satiety centre neuronal activity. This suggests that changes in the amino acid concentration of blood have the same effect on food intake as glucose alterations in other animals.

The Lipostat Theory

Unlike the glucostat theory, it is thought that the lipostat theory controls long-term appetite – the cumulative effect over time of many meals. This therefore makes it responsible for the control of body weight.

As fat deposits accumulate, satiety signals are sent to the hypothalamus in response in an attempt to suppress the feeling of hunger and maintain a constant body weight. Leptin and other hormones act as satiety signals and are released from fat cells in proportion to the size of the cells. This means that as an animal becomes fatter, the amount of leptin secreted increases. As leptin acts as a satiety signal, the increased amounts are detected by the hypothalamus which in turns increases satiety neuronal activity. The activity of these neurons decreases the feeling of hunger so the animal should consume less, remove the extra weight and return to its set weight.

Factors Affecting Food Intake

The breaking down of the hypothalamus’ control of appetite into the satiety and appetite centres is only a simplistic view, in reality there are a multitude of factors responsible. These factors are typically split into two categories, orexigenic (factors which make the animal eat more) and anorexigenic (factors which make the animal eat less). A few examples of these factors are given below:

Adipose Hormones

Leptin is the main hormone associated with adipose control of appetite, seen in many animals (not just mammals) it is released in greater quantities from fatter animals in an attempt to reduce appetite. Leptin binds to receptors in the arcuate nucleus (found in the hypothalamus). The binding suppresses appetite and stimulates the metabolic rate which act together to produce weight loss. In animals which hibernate, these signals are ignored during the autumn to allow the animal to consume enough food to build up energy stores which will last over winter.

Adiponectin is secreted in greater amounts by the fat of leaner animals than obese animals. It is believed to have opposing functions of leptin i.e. stimulate hunger when released in greater quantities.

Brain Signals in the Arcuate Nucleus

The many chemical messengers which control food intake are stimulated by lectin in some manner. The chemical messengers that increase food consumption also promote weight gain by stimulating sympathetic nervous system activity; those which decrease food consumption also promote weight loss by inhibiting sympathetic nervous system activity.

The arcuate nucleus contains two major subsets of neurons which are regulated by leptin in an opposing manner. One releases neuropeptide Y (NPY) and the other, a family of hormones known as the melanocortins.

NPY is a powerful appetite stimulator, therefore leptin is able to suppress food intake by inhibiting the secretion of the hunger inducing NPY from the arcuate nucleus. The opposite is also true, when leptin levels are low (such as after weight loss) NPY is no longer inhibited and the hunger inducing neuropeptide results in increased levels of food consumption.

The melanocortins are able to decrease food intake. When fat stores rise and leptin is released in higher quantities, arcuate neurons which secrete these melanocortins are stimulated – decreasing food intake and weight. This occurs simultaneously with the inhibition of arcuate neurons which produce NPY by leptin.

Brain Signals in other Hypothalamic Nuclei

Two other hypothalamic regions involved in appetite project from the arcuate neurons. These are the paraventricular nucleus (PVN) and the lateral hypothalamic area (LHA).

  • The LHA produces orexins which are powerful neuropeptide stimulators of feeding; their release is stimulated by NPY and inhibited by melanocortins signals.
  • The PVN releases corticotrophin-releasing hormone (CRH) which is an appetite suppressor, its release is stimulated by melanocortins but inhibited by NPY.

Sensory Messages Received by the Brainstem

The nucleus of the solitary tract in the brainstem integrates sensory messages from the digestive tract, via the vagus nerve, with hypothalamic inputs to signal to the animal to terminate a meal. Also stretch stimulation of the stomach (gastric stretch receptors) can inhibit hunger, whilst conversely when not stretched, the receptors may stimulate hunger.

Gastrointestinal Hormones

The gastrointestinal tract can produce hormones which affect the appetite:

  • Cholecystokinin (CCK) – Released from the duodenum in response to the presence of nutrients in the small intestine.
  • Ghrelin – Secreted by the stomach when empty
  • PYY3-36 – Secreted by the stomach when full

These chemicals can allow the animal to feel full, before a meal has been fully digested in order to prevent overeating.

Glucose & Insulin

In mammals glucose levels alter rapidly during feeding. High blood-glucose levels indicate satiety to the body, whilst low levels indicate hunger. Insulin is released from the pancreas in response to a rise in blood glucose levels, causing uptake of glucose into tissue. Insulin is therefore acts as a satiety signal.

Psychosocial & Environmental Influences

Eating habits may be effected by other influences as well:

  • Palatability – If a food substance tastes good, the organism will derive pleasure from eating it and hence reinforce this behaviour. This could result in overeating.
  • Stress
  • Boredom
  • Reduced physical activity



Cellular Anatomy of the Nervous System

Neuronal Structure

Function of Main Neuronal Components:

  • Soma – The bulbous end of a neuron, containing the cell nucleus. Sometimes referred to as the cell body, it is the ‘control centre’ of the neurone
  • Dendrites – The branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. They are what receive the input to the neurone.
  • Axon – The slender projection of a nerve cell, or neuron, which conducts electrical impulses away from the neuron’s cell body or soma. They are responsible for sending neurone output to the connecting CNS areas.
  • Axon Hillock – Connects the cell body (the soma) to the axon. This is where action potentials are generated.
  • Myelin Sheath – An electrically insulating material that typically forms a layer around the axon of a neuron. They are able to increase the speed at which action potentials are propagated.
  • Mitochondria – Provide the neurone with chemical energy from respiration.
  • Endoplasmic Reticulum (ER) – Synthesise proteins within the soma.
  • Golgi apparatus – Processes proteins formed by the ER to make them functional, this often includes the process of glycosylation which helps in proper folding of proteins, stability and cell to cell adhesion.
  • Nissl Substance ­- Large granular bodies found in neurons which contain RNA involved in the production of proteins.
  • Microfilaments – The thinnest (actin) filaments of the cytoskeleton found in the cytoplasm of all eukaryotic cells.
  • Neurofilaments – Intermediate sized, protein filaments found specifically in neurons.
  • Microtubules – Microtubules serve as thick, structural components within cells which are also involved in transport.

Identifying Neurones

Bright-field Microscopy & Staining

Golgi Method

The axon and the dendrites of a neurone are too slender and transparent to be seen with normal staining techniques. Golgi’s method stains a limited number of cells at random in their entirety. (The mechanism is still not entirely known). Dendrites, as well as the cell soma, are clearly stained in brown and black and can be followed along their entire length. Enabling the tracking of connections between neurons and making the complex networking structure of many parts of the brain and spinal cord visible.

Nissl Stain

The Nissl stain uses basic aniline to stain RNA blue, and is used to highlight important structural features of neurons. The Nissl substance (rough endoplasmic reticulum) appears dark blue due to the staining of ribosomal RNA, giving the cytoplasm a mottled appearance. Individual granules of extranuclear RNA are named Nissl granules (ribosomes). DNA present in the nucleus stains a similar colour. The cell bodies and proximal dendrites may also be observed.

The Weigert Method

A staining solution of ferric chloride and haematoxylin; myelin stains deep blue, degenerated portions light yellow. This allows the tracking of myelinated fibres.

Immunohistochemical Staining

Immunohistochemical staining involves the use of fluorescent substances to locate specific antigens. A fluorescent ‘tag’ is attached to an antibody, this antibody is then either; directly released onto a substance where it binds to its specific antigen or, an initial antibody binds to the antigen being probed for and the fluorescently tagged antibody then binds to the initial antibody.

Once the antibodies have bound to the antigen, the specific antigen being probed for will then appear to fluoresce under specific light.

Electron Microscopy

Much more powerful than light microscopes, electron microscopes can magnify up to 1,000,000 times. This enables neurone structure to be viewed in very fine detail.

Idealised Neurone Types

The three basic types of idealised neurones include; bipolar, (Pseudo) unipolar and multipolar neurones, their name indicating the number of exits from the soma. Typically these neurones are found in different places around the body:

  • Bipolar – Specialized sensory neurons for the transmission of special senses. As such, they are part of the sensory pathways for smell, sight, taste, hearing and vestibular functions. The most common example are the bipolar neurones found in the retina
  • (Pseudo) Unipolar – Although there appear to be two ends to the unipolar neurone, (such as that observed in the bipolar neurone) there is originally only one exit from the soma, hence the pseudo- often prefixing unipolar. Many types of primary sensory neurones are unipolar.
  • Multipolar – Multipolar neurons constitute the majority of neurons in the brain and include motor neurones and interneurones.

Glial Cells

Glial cells are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for the brain’s neurons. The four main functions of glial cells are to surround neurons and hold them in place, to supply nutrients and oxygen to neurons, to insulate one neuron from another, and to destroy pathogens and remove dead neurons. They also modulate neurotransmission.

Astrocytes

Astrocytes are star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells which form the blood-brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a principal role in the repair and scarring process of the brain and spinal cord following traumatic injuries.

It is thought that astrocytes are able to take up glucose from blood vessels and redistribute it to neurones, giving them the nutritional support they require. They can also take up neurotransmitters and ‘detoxify’ them.

Oligodendrocytes

The main function of Oligodendrocytes is the insulation of axons to form Nodes of Ranvier. These nodes are breaks between the insulation of the axon which allow action potentials to jump between them thus increasing the speed of action potential transmission. The speed at which action potentials travel along myelinated axons increases linearly in relation to the diameter. (In unmyelinated axons, speed increases only with the square root of the diameter.)

Microglia

Microglia are a type of glial cells that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defence in the central nervous system (CNS). Microglia are constantly excavating the CNS for damaged neurons, plaques, and infectious agents. The brain and spinal cord are separated from the rest of the body by the blood-brain barrier, which prevents most infections from reaching the vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood-brain barrier, microglial cells must react quickly to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (few antibodies cross the blood brain barrier due to their large size), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells. Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS.

Ependymal Cells

Ependymal cells are epithelial cells that line the cerebrospinal fluid (CSF)-filled ventricles in the brain and the central canal of the spinal cord. Their apical surfaces are covered in a layer of cilia, which circulate CSF around the central nervous system. Their apical surfaces are also covered with microvilli, which absorb CSF. Ependymal cells can also produce CSF.