GEP (Life Control) Week 2 Flashcards
What are the 3 main structures of the brain and their roles
Cerebrum (cerebral cortex)
Cerebellum
Brainstem
Cerebrum: is the largest part of the brain and is composed of right and left hemispheres. It performs higher functions like interpreting touch, vision and hearing, as well as speech, reasoning, emotions, learning, and fine control of movement.
Cerebellum: is located under the cerebrum. Its function is to coordinate muscle movements, maintain posture, and balance.
Brainstem: acts as a relay center connecting the cerebrum and cerebellum to the spinal cord. It performs many automatic functions such as breathing, heart rate, body temperature, wake and sleep cycles, digestion, sneezing, coughing, vomiting, and swallowing.
Explain further what the cerebrum consists of
Cerebral cortex
●The bulk of the brain is made up of the cerebrum: the name given to the two cerebral hemispheres. Each cerebral hemisphere consists of an outer layer of grey matter (the cerebral cortex) and an inner mass of mostly white matter.
●Each cerebral hemisphere also has several masses of cell bodies within the subcortical white matter
●The cerebral cortex is composed of grey matter (neuronal cell bodies).
●It is divided into four lobes: frontal, parietal, temporal, occipital.
●The cerebral cortex has a highly convoluted structure (maximises cortical surface area). It is folded into elevations or ridges, called gyri - (sing. gyrus), separated by grooves/depressions called sulci (sing. Sulcus).
What are the main sulci and gyri used to help identify different anatomical landmarks
Central Sulcus: divides frontal and parietal lobes
Lateral Sulcus: divides frontal and temporal lobes
Pre-central Gyrus: Primary motor cortex, controls voluntary movement, origin of descending motor pathways
Post-central Gyrus: Primary somatosensory cortex, terminus of all ascending sensory pathways
DO FIRST, THINK LATER
Cerebral cortex control of movement and sensation
-Some gyri and sulci mark the location of important functional areas or anatomical divisions of the cortex.
-Two important sulci are: The central sulcus, which divides the frontal lobe (here in blue) from the parietal lobe (here in yellow)
-And the lateral sulcus (or fissure) divides the temporal lobe (here in green) from the frontal and parietal lobes.
-The central sulcus marks out two very important gyri which are relevant for this week.
-The gyrus immediately in front of the central sulcus is the pre-central gyrus. Functionally, it comprises the primary motor cortex – the location of the highest level control of voluntary movement.
-The gyrus immediately behind the central sulcus is the post-central gyrus. Functionally, this area is the primary somatosensory cortex, which receives sensory information from all over the body. It is where all of the pathways for touch, pressure, pain and temperature terminate.
Desribe the segments of the spine, the amount of regions and what dorsal and ventral means
- 31 segments over 4 regions. Shape changes over regions
- Each segment has a pair of spinal nerve
- Each pair contains a dorsal and ventral nerve root
- Ventral: ANS and efferent motor neurons. Exit the spinal cord anteriorly
- MOVE!!
- Dorsal: Afferent sensory neurons. Enter the spinal cord posteriorly
- Dorsal root also contain dorsal root ganglion - cell bodies of neurons but no synapse!
- Roots join to form bi-directional spinal nerve
- Afferent = arriving at the CNS
- Efferent = exiting the CNS (Eff off)
As you can see from this diagram, the spinal cord sits within the vertebral/spinal canal within the vertebral column. Like the brain, it is covered by three layers of meninges: the tough, fibrous outer dura mater. Beneath that, the arachnoid mater, underneath which is the subarachnoid space filled with CSF. And then the pia mater, which is attached to the spinal cord itself.
The spinal cord has 31 segments (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal) each with a corresponding pair of spinal nerves entering/exiting.
The injury was C7 which means lower body and potentially breathing are affected
Each nerve has a dorsal and ventral root.
Ventral nerve roots: exit the spinal cord anteriorly. Contain efferent motor neurons (and neurons of the autonomic nervous system – more on this to come). (MOtor VEntral)
Dorsal nerve roots: enter spinal cord posteriorly. Contain fibres of afferent sensory neurons.
The dorsal root also contains the dorsal root ganglion – which contains the cell bodies of the peripheral sensory neurons (the primary afferent neurons). These ganglia appear as small enlargements on the dorsal roots. (NB the cell bodies of the efferent motor neurons are located in the grey matter of the spinal cord.
These roots join at or near the intervertebral foramina to form a mixed spinal nerve proper – mixed because it contains both afferent and efferent neurons.
Where is the white matter and grey matter in the spinal cord
Describe the anatomy of the spinal cord
H-shaped grey matter surrounded by white matter
Grey matter houses cell bodies:
Ventral Horn - Motor neurons (anterior horn cells)
Dorsal Horn - Sensory neurons
Lateral Horn - Preganglionic sensory neurons (present in cervical and thoracic regions)
White matter houses
Descending and ascending tracts of neuronal axons.
Can be subdivided into three columns called funiculi: dorsal, ventral and lateral
Internal structure of the spinal cord
●H-shaped inner core of grey matter – H-shaped, or butterfly-shaped. This mainly contains nerve cell bodies and synapses (as well as some communicating neurons). It has four “horns”: two dorsal (posterior) and two ventral (anterior).
*The dorsal (posterior) horns contain sensory neurons that receive afferent projections from the dorsal root ganglia.
*The ventral (anterior) horns contain longitudinal columns of motor neurons that innervate the skeletal musculature via the ventral roots
●Afferent sensory nerve fibres entering via the dorsal roots terminate in the dorsal horns.
●The ventral horn contains cell bodies of motor neurons that exit through the ventral nerve roots and innervate skeletal muscle.
●Lateral horn = thoracic and upper lumbar segments only – cell bodies of preganglionic sympathetic neurons.
●The grey matter core is surrounded by white matter, containing ascending and descending nerve fibres between the cord and the brain, as well as fibres running between different sections of the cord.
*The surrounding white matter can be subdivided into ventral (anterior), dorsal (posterior) and lateral columns, called funiculi (singular = funiculus, means string in latin)
*The shapes and sizes of these divisions/regions will look slightly different depending on which level of the spinal cord you are looking at so bare that in mind when looking at spinal cord sections
●Within these three divisions there are further divisions where groups of fibres running together are grouped in fascicles (bundles of axons), forming somewhat discreet tracts in the spinal cord. More on this on the next slide.
●Composition of grey and white matter varies by level of the spinal cord. For example, the dorsal and ventral horns are particularly prominent at the cervical and lumbar levels due to innervation of the upper and lower limbs (lots of afferent/efferent neurons synapsing).
●Picture = lumbar vertebra.
What are the 3 main CNS/Pathways in the spine
1.Corticospinal tract (motor) - descending
2.Dorsal column (sensory) - ascending
●Cuneatus is upper half (C before G)
3.Spinothalamic (sensory) - ascending
What is a spinal tract
Ascending and descending spinal tracts are pathways that carry information up and down the spinal cord between brain and body.
The ascending tracts carry sensory information from the body, like pain, for example, up the spinal cord to the brain.
Descending tracts carry motor information, like instructions to move the arm, from the brain down the spinal cord to the body.
Both types of tracts are made up of neuronal axons that gather into long columns called funiculi.
What does Decussate, Contralateral and Ipsilateral mean
Decussate: Crossing over
Contralateral: Opposite side
Ipsilateral: Same side
What areas are the sensory and motor called in the spinal cord
Describe the overview of the desending tract, how it seperates
The descending tracts of the nervous system are the pathways by which motor signals are sent from the brain to lower motor neurons.
Pyramidal tracts are called pyramidal as they pass through the pyramids of the medulla oblongata.
What do the the cortiospinal and corticobulbar tract control
Pyramidal (Primary motor pathway: Voluntary control of skeletal muscle)
Corticospinal Tract: Supplies the musculature of the body.
Anterior Corticospinal: Voluntary movements of the trunk and shoulders.
Lateral Corticospinal: Voluntary movements of the limbs.
Corticobulbar Tract: Supplies the musculature of the head and neck.
The descending tracts of the nervous system are the pathways by which motor signals are sent from the brain to lower motor neurons.
The motor tracts can be functionally divided into 2 main groups: pyramidal tracts (originate from cerebral cortex): responsible for voluntary control of skeletal muscle in body and face. The pyramidal tracts get their name from the pyramids of the medulla which they pass through
Extrapyramidal tracts (originate in brain stem): responsible for involuntary and automatic control of all musculature: muscle tone, balance, posture, locomotion.
What does pyramidal and extrapyramidal mean
The descending tracts of the nervous system are the pathways by which motor signals are sent from the brain to lower motor neurons.
The motor tracts can be functionally divided into 2 main groups: pyramidal tracts (originate from cerebral cortex): responsible for voluntary control of skeletal muscle in body and face. The pyramidal tracts get their name from the pyramids of the medulla which they pass through
Extrapyramidal tracts (originate in brain stem): responsible for involuntary and automatic control of all musculature: muscle tone, balance, posture, locomotion.
Where is the motor control located and describe the different types of motor cortex
Motor cortex is located in the precentral gyrus
Primary Motor Cortex: Starting point for descending motor pathways controlling voluntary movement of the opposite side of the body.
Premotor Cortex: Involved in movement planning and preparation.
The primary Motor cortex contains a point-to-point map of the contralateral side of the body, called a somatotopic representation.
The size of the cortex devoted to each body part is proportional to the provision of motor control.
What are motor tracts? and what are lower and upper motor neurones
Upper motor neurons (CNS): Cell body in the cortex or brain stem. Axon descends in one of the descending motor tracts to synapse on lower motor neuron in the grey matter of the spinal cord.
Lower motor neuron (PNS): Cell body in ventral horn of grey matter. Axons travel in peripheral nerve to reach target muscle. This is the final common pathway for all movements, both voluntary and reflexive.
Motor control
In these descending tracts, motor control can be thought of as a 2-neuron pathway.
There are two neurons in the pathway: an upper motor neuron, which is entirely within the central nervous system 🡪 originates in a motor area in the cerebral cortex or brain stem, descends in one of the tracts to synapse on a lower motor neuron.
LMNs have their cell body in the ventral horn of grey matter in the spinal cord, and their axons travel in a peripheral nerve to reach their target muscle. Lower motor neurons directly innervate muscles to produce movement.
Different transverse slice diagram I.e useful in CT scans etc
What is the corticospinal tract
The corticospinal tract is the major neuronal pathway providing voluntary motor function. This tract connects the cortex to the spinal cord to enable movement of the distal extremities.
Anterior Corticospinal: Voluntary movement of the trunk and shoulders.
Lateral Corticospinal: Voluntary movements of the limbs.
Describe the upper motor corticospinal tract pathway
The corticospinal tract supplies the musculature of the body
Corticospinal tract fibres leave cerebral cortex. Pass through the corona radiata and down through posterior limb of the internal capsule (between thalamus and lentiform nucleus of basal ganglia)
Descends through anterior part of brain stem through crus cerebri (anterior portion of midbrain), basilar pons and pyramids of the medulla.
Decussate (80-90% fibres) at lowermost border of medulla – fibres pass posteriorly and laterally to become lateral corticospinal tract.
Remaining 10% of fibres continue anteriorly as the anterior corticospinal tract (many of these fibres still cross the midline close to their point of termination).
Anterior corticospinal tract: supplies proximal/axial musculature (gross motor).
Lateral corticospinal tract: distal musculature (fine movts)
How does the nerve go from 1st order to 2nd order neuron
After travelling through the brain into the spinal cord the 1st order neuron will decussate to the contralateral side.
Once decussated the upper motor neuron will synapse With the lower motor neuron which will then continue the signal to the effector.
How does the lower motor neurone innervate skeletal muscles
This is the second order neuron
Neuromuscular junction = point of contact between lower motor neuron and skeletal muscle fibre (Similar to a synapse). Ach released from LMN acts on nicotinic Ach Receptors.
Motor unit = a single lower motor neuron and the multiple muscle fibres it innervates simultaneously.
Large motor unit = more muscle fibres innervated = high power, low precision. E.g. axial muscles of the trunk: 1 LMN may innervate >1000 fibres.
Small motor unit = fewer muscle fibres innervated = high precision, low power e.g. eyes and hand; 1 LMn may innervate <10 muscle fibres.
In regards to muscle tone and reflex, what does upper and lower mean
Upper = Brain or spinal cord.
Lower = Anterior horn cell, motor nerve roots or peripheral motor nerve.
Muscle tone helps maintain posture and joint stability.
It is mediated by the stretch reflex: muscles contract automatically in response to being stretched, resisting passive changes in length.
This motor reflex arc occurs involuntarily, without any stimulation from the brain. It is lost in lower motor neuron lesions resulting in weakness, hypotonia and areflexia.
Sensitivity of the stretch reflex is normally regulated by descending projections from the brain stem (reticular formation). This is lost in upper motor neuron lesions. Without this, there can be too much resting muscle tone
(hypertonia/spasticity) and overactive reflexes (Hyperreflexia).
Upper motor neuron lesions = Hyperreflexia.
Lower motor neuron lesions = Areflexia.
What is muscle tone
Muscle tone is the resting tension in a skeletal muscle. It occurs because there are always a few motor units contracting in a resting muscle. These contractions do not cause enough tension to produce movement. Muscle tone is maintained by a normal reflex arc, whereby a signal is sent from the muscle spindles to a lower motor neuron in the posterior root ganglion which then sends a signal to the appropriate muscles to adjust the extent of their contraction. Changes in tension in a muscle result in activation of the muscle spindles so that the contraction of other muscles is altered to correct the tension in that muscle. This reflex arc is also under the control of the central nervous system.
Resting muscle tone is important for maintaining normal posture, and provides support for the joints to stabilize their position and help prevent sudden changes in the position. Muscle tone is increased in upper motor neuron lesions, for example in cerebral cortical damage that occurs in cerebrovascular accident. This is thought to be due to loss of cortical control of motor neurons, which increase their activity. There is no muscle wasting. A reduction in muscle tone, hypotonia, occurs in lower motor neuron disorders. These occur in spinal and/or peripheral nerve damage. This results in muscle atrophy. Examination of muscle tone provides important clues to the cause of muscle weakness.
What is an upper and lower motor neuron lesion and what can cause it
Pyramidal weakness:Weakness that preferentially spares the antigravity muscles.
Clonus: Muscular spasms involving repeated, often rhythmic contractions.
Fasciculations: Brief spontaneous contraction affecting a small number of muscle fibres, often causing a flicker of movement under the skin.
Describe the corticobulbar tract
Corticobulbar tract fibres originate in the primary motor cortex and premotor cortex (mainly face and tongue areas)
Travels with corticospinal tract: through internal capsule into anterior portion of midbrain (Crus cerebri)
Descends anteriorly through the brain stem. Fibres divide off to reach their target motor nuclei of cranial nerves (V, VII, IX, X, XI, XII).
Controls muscles of jaw, facial expression, speech, swallowing and movements of the neck.
Where in the cortex is the sensory cortex located
Precentral Gyrus = Motor.
Postcentral Gyrus = Sensory
Give an overview of the dorsal column pathway
1st order neuron travels from end organ, enters spinal cord and travels up until it reaches the medulla.
All 1st order neurons synapse with 2nd order neurons at the level of the medulla. 2nd order neurons decussate then continue to thalamus where they synapse with 3rd order neurons
3rd order neurons at thalamus carries fibres to higher association areas (somatosensory cortex).
Give an overview of the detailed column pathway
Receptors: Meissner’s/merkel’s/tendon organs/ muscle spindle (mechano and proprio receptors)
In spinal cord: fibres from lower half of the body below T6, ascend in the medial part of the dorsal column: Gracile fasciculus.
Fibres from the upper half of the body, above T6 ascend in the lateral part of the dorsal column: Cuneate fasciculus.
In the brainstem, 1st order neurons pass through the dorsal column (Gracile fasciculus and cuneate fasciculus), to reach the gracile and cuneate nuclei in the medulla. Here they synapse with second-order neurons.
2nd order neurons form internal arcuate fibres in medulla -> decussate over to the opposite side. They then ascend through the brainstem as medial lemniscus.
In cerebrum the medial lemniscus terminates on the ventral posterolateral nucleus of the thalamus by synapsing to the 3rd order neuron. The 3rd order neuron travels through the posterior limb of the internal capsule and onto the primary somatosensory cortex.
Give an overview of how the spinothalamic tract works
1st order neuron enters the dorsal root of the spinal cord posteriorly and synapses with the 2nd order neuron.
The 2nd order neuron then decussates at the level, above or below the level of spinal cord entry to the contralateral side and continues to the thalamus.
The 2nd order neuron synapses with the 3rd order neuron at the thalamus which carries fibres to the higher association areas (somatosensory cortex)
What is the main difference between the lateral and anterior spinothalamic tract
Lateral Spinothalamic tract= Transmits pain and temperature.
Anterior Spinothalamic tract= Transmits crude touch and firm pressure.
Not a question just an overview of the different spinal tract
Table of the different spinal tract
What happens if there is damage to the dorsal column and the spinothalamic
Dorsal Column
Crosses over at medulla, after it has travelled through the spinal cord, so if lesion below the medulla in the spinal cord then the nerve fibres damaged will be on the SAME side as the innervated tissues.
Damage to dorsal column will result in loss of fine touch and proprioception.
Spinothalamic
Crosses over immediately to other side so if lesion above this point damaging the nerve fibres it will lead to loss of innervation to the OPPOSITE side.
Damage to anterior will result in loss of crude touch and firm pressure.
Damage to lateral results in loss of pain and temp.
What are spinal cord syndromes
Several classic syndromes that have characteristic clinical features based on the area of the spinal cord that is affected.
Neurological signs and symptoms can usually be located to the spinal cord based on the presentation of bilateral motor and sensory signs without head or face involvement.
In some situations, a specific set of clinical features can develop due to the area within the spinal cord that is affected.
Main causes of spinal cord injury are road traffic collisions falls, violent attacks, sporting injuries and domestic accidents.
How do you test the spinal cord tracts
The 128 Hz tuning fork is used for vibration testing (the little one).
Give an overview of how the nervous system is broken down into different parts
*we’re now talking about the autonomic division of the PNS, also called the viscero-motor system.
*It regulates the contraction of cardiac and smooth muscle and the secretory activity of glands – via two divisions, sympathetic and parasympathetic, which tend to have opposing effects on a given organ or tissue
What is the autonomic nervous system
- Split into sympathetic and parasympathetic
- Controlled by the hypothalamus
- Both types originate from different regions of the spinal cord
-Sympathetic Thoracolumbar -> sympathetic chain
-Parasympathetic Craniosacral - Parasympathetic cranial nerves are:
-Occulomotor (III) - Facial (VII)
- Glossopharyngeal (IX)
- Vagus (X)
- 3+7=10 not 9!!
- No “sympathetic” cranial nerves (some have sympathetic links)
ANS is controlled by the hypothalamus – located in base/sides of the walls of the third ventricle
The sympathetic and parasympathetic divisions of the ANS have distinct anatomical origins in the CNS.
Sympathetic fibres originate in the thoracic and upper lumbar segments of the spinal cord (T1–L2 or 3). This is termed the “thoracolumbar outflow”. They leave the spinal cord and enter something called the sympathetic chain or trunk on either side of the vertebral column.
Parasympathetic fibres originate from opposite ends of the CNS in four of the cranial nerves and the sacral spinal cord. This is called the “cranio-sacral outflow”:
Four cranial nerves carry parasympathetic fibres – III (oculomotor), VII (facial), IX (glossopharyngeal) and X (Vagus)
Cell bodies in CN nucleus → preganglionic axon travels with the associated cranial nerve → synapses onto autonomic ganglia near the target organ.
4/12 cranial nerves carry PNS fibres;
1. Oculomotor (CN III): → pupil constrictor muscle of the eye (pupillary light reflexes)
2. Facial (CN VII): salivary and lacrimal (eye) glands (except parotid salivary gland)
3. Glossopharyngeal (CN IX): → salivary and lacrimal (eye) glands
4. Vagus (CN X): principal parasympathetic nerve for the entire body – it has a very wide territory (vagus = “wandering” in latin) & supplies organs in the thorax and abdomen via autonomic plexuses which lie close to the heart, lungs, stomach and intestines.
The sacral outflow of the parasympathetic system as the pelvic splanchnic nerves and innervates the bladder, large intestine and genitalia
Known as “fight or flight” or “rest and digest”.
What is the sympathetic chain
The sympathetic trunks (sympathetic chain, gangliated cord) are a paired bundle of nerve fibres that run from the base of the skull to the coccyx. The sympathetic motorway
One either side of the spinal cord
The synapse area for pre → post-ganglionic fibres
SNS: how does sympathetic supply reach body from its outflow only from T1-L2? Via the sympathetic chain. They enter the sympathetic chain, which is a chain of autonomic ganglia located on either side of the vertebral column and enables sympathetic innervation to the entire body. Remember ganglia = collection of cell bodies.
How does the sympathetic chain work
Preganglionic sympathetic neuron leaves CNS via ventral root (anterior horn)
Travels via white rami communicantes to sympathetic chain.
From here they can:
Synapse at the same level & continue to spinal nerve via grey rami communicantes
Move along the chain before synapsing
Pass through, synapsing only after travelling to the gut/pelvic area
Remember: two neuron chain: preganglionic and postganglionic.
SNS has longer post-ganglionic shorter pre-ganglionic, PNS is vice versa
The first neuron, the preganglionic has its cell body in the spinal cord.
The preganglionic SNS neuron leaves spinal cord via ventral root (at the front). Joins the mixed spinal nerve. But then peels off and travels down something called the white rami communicantes.
From there, 3 pathways for SNS neurons (Imagine a motorway junction coming off the slip road to the roundabout):
○1. Synapse in sympathetic ganglion at that level. Postganglionic fibre then re-enters the spinal nerve through the grey rami communicantes (Join the A-road)
○2. Travel up or down the chain to synapse in a ganglion higher or lower down (the motorway slip road no one uses to go one junction further).
○3. Pass through the chain without synapsing and travel towards the gut. There it will synapse in another abdominal ganglion closer to the target organ (coeliac ganglion, superior mesenteric ganglion, inferior mesenteric ganglion etc) (take the B-roads into town).
Describe the nerve transmission with somatic nervous system and the ANS.
The ganglia are just clusters of neuronal cell bodies that are essentially a junction between autonomic fibres originating from the CNS and autonomic fibres innervating their target organs in the periphery
Sympathetic:
Short pre long post (synapse close to spinal cord)
Post-ganglionic neurotransmitter is mainly noradrenaline (adrenaline also…), acting at alpha and beta adrenergic receptors at the end organ
Parasympathetic
Long pre short post (think vagus nerve) (synapse close to peripheries)
Post-ganglionic neurotransmitter is acetylcholine, acting at muscarinic receptors at the end organ
Describe the different autonomic metabotrophic receptors
●M1-5
○M1 on neurons, gastric glands
○M2 cardiac cells
○M3 smooth muscle of eye, GIT, lungs, exocrine glands eg salivary glands
●GPCRs – M1 and M3 coupled to Gαq = lead to increase in intracellular levels of calcium -> trigger contraction, secretions and neurotransmission
○Vs M2 coupled to Gαi = opening of K+ channels -> hyperpolarization and reduction of heart rate
●NICOTINIC – ligand gated, when agonist binds undergo conformational change to allow sodium into cells
Nicotinic receptors function within the central nervous system and at the neuromuscular junction. While muscarinic receptors function in both the peripheral and central nervous systems, mediating innervation to visceral organs
○NM on neuromuscular junction – contraction
○NN in CNS and autonomic ganglia – transmission of cholinergic signals
What are the main differences betweem sympathetic and parasympathetic
How is a action potential formed
The formation of an action potential can be divided into five steps:
(1) A stimulus from a sensory cell or another neuron causes the target cell to depolarize toward the threshold potential.
(2) If the threshold of excitation is reached, all Na+ channels open and the membrane depolarizes.
(3) At the peak action potential, K+ channels open and K+ begins to leave the cell. At the same time, Na+ channels close.
(4) The membrane becomes hyperpolarized as K+ ions continue to leave the cell. The hyperpolarized membrane is in a refractory period and cannot fire.
(5) The K+ channels close and the Na+/K+ transporter restores the resting potential.
What occurs at thet synapse during an action potential
Neurotransmitter release
Calcium mediated
Normally Acetylcholine (ACh)
Binds to post-synaptic ligand-gated ion channels
Communication at chemical synapses requires release of neurotransmitters. When the presynaptic membrane is depolarized, voltage-gated Ca2+ channels open and allow Ca2+ to enter the cell. The calcium entry causes synaptic vesicles to fuse with the membrane and release neurotransmitter molecules into the synaptic cleft. The neurotransmitter diffuses across the synaptic cleft and binds to ligand-gated ion channels in the postsynaptic membrane, resulting in a localized depolarization or hyperpolarization of the postsynaptic neauron.
How can drugs affect the action of nerve transmission and action potential
Drugs can target the following sites:
Neurotransmitter synthesis
Neurotransmitter vesicular storage
Arrival of action potential at synaptic terminal
Depolarisation of terminal to activate VGCC and influx of Ca2+ ions
Ca2+ dependent release of neurotransmitter
Neurotransmitter binding to receptor (to induce response)
Uptake/breakdown of neurotransmitter
Receptor: Memantine NMDA receptor antagonist (moderate to severe Alzheimer’s). Reduced glutamate mediated neurotoxicity
Uptake/breakdown: SSRIs. Block reuptake of serotonin (5-HT) in synaptic cleft, Does this via blocking SERT receptor on presynaptic neuron, Increase amount of serotonin IN THE SYNAPTIC CLEFT – does not increase overall NUMBER of 5-HT neurotransmitters
Examples: Sertraline, fluoxetine, citalopram, fluvoxamine
Arrival of action potential: Drugs can block voltage-dependent Na+ channels → prevent action potential generation and propagation along axon → stop pre-synaptic terminal depolarisation and inhibit synaptic transmission.
E.g. Lignocaine (Local anaesthetic) Prevents action potential conduction and synaptic transmission in sensory nerves and stops inputs to the brain coding for pain → no pain sensation
E.g. Anti-epileptics (Phenytoin) Prevents excess synaptic transmission during high-frequency firing in CNS associated with seizures
Ca2+ release
Drugs can block voltage-gated Ca2+ channels → prevent Ca2+ influx → prevent release of neurotransmitter → inhibit synaptic transmission
E.g. Ziconotide (analgesic)
Synthetic form of w-conotoxin (marine cone snail) potent blocker of voltage-gated calcium (Ca2+) channels that is more potent than morphine
*Prevents synaptic release of transmitters involved in conduction of pain signals
*Treatment of chronic severe chronic pain via intrathecal injection
What is the Adrenergic system
Major sympathetic NT - both CNS & PNS
Roles in attention, arousal, sleep and wakefulness
Activate metabotropic alpha & beta adrenergic receptors
COMT deactivates, MAO breakdown in vesicles
*Noradrenaline synthesised via a multi-step pathway, with dopamine converted to noradrenaline via dopamine hydroxylase – noradrenaline can be converted to adrenaline via PNMT in the adrenal medulla
○Influx of calcium causes synaptic vesicle to fuse with presynaptic membrane and release neurotransmitters into synaptic cleft
○NA binds to postsynaptic receptor -> intracellular response
○NA binds to presynaptic receptor which reduces NA release via –ve feedback
○NA removed from synaptic cleft by diffusing into systemic circulation, deactivated by COMT or transported back into neuron by NET
○Can be transported back to vesicles or broken down by monoamine oxidase (MAO)
How do you target the adrenergic system
Drugs can Target:
Vesicular neurotransmitter storage: Reserpine
Ca2+ mediated release of neurotransmitter
Indirect sympathomimetics: Tyramine, Amphetamines
Inhibition of noradrenergic transmission: Guanethidine, Clonidine
Neurotransmitter uptake and breakdown: TCAs, MAO-I
Reserpine: Alpha blocker
Inhibits Vesicular monoamine transporter (VMAT) (stops vesicles taking up noradrenaline)
Progressively reduces amount of noradrenaline ready for release, reducing noradrenergic neurotransmission
Treatment for HTN
Indirect sympathomimetics – mimic the effects of endogenous agonists on sympathetic nervous system → increase heart rate, total peripheral resistance, cardiac output and blood pressure
Tyramine dietary constituent (cheese, meats), enters synaptic cleft by displacing NA in synaptic terminal
Inactivated by MAO. “cheese reaction” when people on MAO-I
Amphetamines taken up by VMAT making vesicles non functional - NA accumulates in cytosol
Can lead to reversal of NA transporte. Leads to release of NA into synaptic cleft (sympathetic effect). Used as a treatment of ADHD
Inhibition of noradrenergic neurotransmission → reduce blood pressure
Guanethidine - taken up into terminal by noradrenaline transporter
Completes with NA for vesicle space → gradually depletes NA vesicular stores
Prevents chemical transmission after chemical impulse (no NA left)
Clonidine stimulates pre-synaptic alpha-2 adrenergic receptors in sympathetic nerve terminals, inhibiting (further) NA release
Reduces sympathetic nerve activity
Uptake/breakdown
Tricyclics (TCAs e.g. amitriptyline) potentiate noradrenergic neurotransmission
Decrease NA and 5-HT reuptake into pre-synaptic terminals → more in synaptic cleft
Prescribed for neuropathic pain etc… No longer for major depression
Monoamine oxidase inhibitors (moclobemide) also potentiate noradrenergic neurotransmission
They increase synaptic cleft levels of monoamine (5-HT, NA, dopamine) neurotransmitters
This is prescribed for depression
What are the main 2 types of Nociceptors
What are the 2 types of pathway for pain and theie neurophysiology
2 Pathways for pain: Lateral, medial
Lateral is the actual feeling of pain: localisation and what pain depending on what area of the somatosensory cortex it localises (alpha delta)
Medial is the uncomfortable feeling uncomfortable. Notice how it does not go to the SS cortex. The midline thalamic nucleus sends the signal to the limbic structures, which will help put the emotion to the stimulus (c-fibres)
All of the neurophysiology steps are there:
Transduction/conduction of the stimuli from the nociceptors into an impulse
Transmission via the CNS afferent pathway to the brain and structures involved with pain
Perception of what and where the pain is
The only part missing is the modulation
What is modulation in relation to the nervous system and how does it work
CNS pain impulses can be modulated by downward pathways
The descending pathways mainly involve grey matter
Modulatory structures sending signals back down the spinal cord
Orbitofrontal/anterior cingulate cortex → spinal cord (periaqueductal grey matter (PAG), Raphe magnus nucleus, locus coeruleus) → +ve 5-HT (inhibitory neuron affects pain fibre synapse)
Some neurons in descending pathway use endogenous opioid neurotransmitters (basis for use of opioids as analgesia).
Bind to opioid receptors
3 types: 𝝻, κ, 𝛌
The role of serotonin in these pathways is also the basis for the use of some antidepressants in chronic pain.
Pathologies can change the descending control and therefore the modulation balance
Other NTs glycine, GABA, serotonin, NA, opioids
Other ways to modulate pain include CBT, placebos & coping, but also acupuncture and Transcutaneous electrical nerve stimulation (TENS) increase downward pathway
Pathologies can increase the balance to increase pain, but also cause increase of downward pathway so no pain can be felt
People can be treated with antidepressants (for pain, mood and coping, but mainly for increasing transmission in anti-nociceptive pathways), benzos for anxiety (increases GABAergic inhibition). Also just general opioids like the natural ones targeting the Mu opioids (other 2 are kappa and lambda)
What are the different types of pain
Functional (somatoform) pain - pain with no organic identifiable origin
Somatic sharp and localised
Visceral is dull, wider area and you can’t pinpoint it
What is reffered pain
In conjunction with visceral pain, but in a different place!
It is somatic pain felt more generally
Happens due to a convergence of somatic nociceptive fibres with visceral ones at the synapse to 2nd order spinothalamic neurons in the spinal cord (they travel up together)
Brain can’t differentiate and mistakes visceral pain as somatic in that area
Best example is an MI, with pain in the left arm and shoulder
Heart nociceptor specifically goes to T3, but can link up anywhere from C7-T5
What is the anatomy of the bladder
Detrusor muscle controls contraction in the bladder, when contracted urine is voided and when relaxed urine is retained.
Sphincters act as physical barriers to stop urine voiding. When contracted urine can’t leave and when relaxed they open for urine to pass.
Males have an anatomical internal and external sphincter whereas females internal sphincter is ‘functional’ rather than anatomical.
Females also have a shorter ureter which also confers an increased risk of UTI’s.
Functional definition:Functional sphincters don’t have a thickened ring of muscles like anatomical sphincters do. Instead, they have a circular muscle that works by constricting either around or inside of them. This specialized structure can’t be visually identified as a sphincter unless it’s constricted.
What controls the bladder
Receptors on the bladder (When stimulated)
M3 receptor = Contraction of detrusor muscle (Parasympathetic) via pelvic nerve.
B3 receptor = Relaxation of detrusor muscle (Sympathetic) via hypogastric nerve.
Alpha 1 receptor = Contraction of internal sphincter (Sympathetic) via via hypogastric nerve.
Nicotinic receptor = Contraction of external Sphincter (Somatic - under voluntary control unlike sympathetic/parasympathetic control) via pudendal nerve.
Sympathetic nervous system prevents you from urinating as you wouldn’t want to urine when you are in fight or flight mode. Parasympathetic allows you to urinate as you would rather urinate when relaxed (probably). The somatic nervous system voluntary controls the external sphincter so you can voluntarily choose when to urinate.
What is the bladder control for voiding and filling
Control of micturition (urination) is coordinated by the micturition centre in the pons
Empty Bladder
Bladder empty, detrusor not stretched = sensory pelvic nerve sends slow impulses towards micturition centre.
Hypogastric nerve (sympathetic nerve) stimulates A1 receptor on internal sphincter (contraction) and B3 receptor causing relaxation of detrusor muscle.
Pudendal nerve (somatic) stimulates nicotinic receptor on external sphincter causing contraction of external sphincter also.
You are not peeing.
Full Bladder
Bladder full, detrusor stretched. Sensory pelvic nerve sends fast signals to micturition centre.
Inhibition of hypogastric nerve = no relaxation of detrusor muscle + relaxation of internal sphincter).
Stimulation of pelvic efferent nerves results in activation of M3 receptor on bladder resulting in contraction of detrusor muscle.
Inhibition of pudendal nerve (somatic) so there is no stimulation of nicotinic receptor resulting in relaxation of external sphincter.
You are now peeing.
What is PTSD and how is it categorised
DSM 5 Criteria for PTSD
Symptoms present for >1 month.
Experienced/witnessed a traumatic event e.g. actual or threatened death, serious injury or sexual violence.
Persistently re-experience at least one of the following intrusive symptoms:
Intrusive or recurring memories.
Dissociative reactions.
Intense or prolonged distress after exposure to traumatic reminders.
Marked physiological reactivity.
Negative changes in mood or thoughts.
Alterations in arousal and reactivity.
Symptoms overall should cause significant distress or functional impairment.
Not be due to other secondary factors e.g. medications.
Key Points
Don’t need to have directly experienced the traumatic event themselves.
An element of re-experiencing the event e.g. nightmares, flashbacks.
Negative symptoms.
