Scenario 24: Healthy Nervous System Flashcards
Describe an electrical synapse
Nerve fibre and dendrite connected by pores through which ions flow down their concentration gradients. Little synaptic delay, bidirectional
Give some examples of where electrical synapses are found
Lateral vestibular nucleus, inferior olive, molecular layer of cerebellum, retina and a few junctions in cerebral cortex
Describe a chemical synapse
Increased extracellular space, no continuity, chemical messenger mediated, more synaptic delay, unidirectional
Where are chemical synapses found?
In the majority of the CNS
Why is there more of a synaptic delay with chemical synapses rather than electrical ones?
It takes time for Ca2+ channels to open, NT to be secreted across the terminal, postsynaptic receptor interaction and 2nd messenger formation
How can synapses be classified by their electron density?
Asymmetrical- more electron dense material on one side
Symmetrical- same amounts on both sides
What are Gray type I synapses?
Have round vesicles, wide synaptic cleft, dense projections, dense polysynaptic dense and large active zone
What are Gray type II synapses?
Have flattened synaptic vesicles, less obvious dense projections, narrow synaptic cleft, 2 postsynaptic densities
Where do Gray type I synapses synapse usually?
Onto shaft or spine (axodendritic)
Where do Gray type II synapses synapse usually?
Onto soma (axosomatic)
How does the distance of a synapse from the axon hillock affect it’s function?
Further away= less effective
Near axon hillock= global effect
How does location of synapses affect function?
Functionally on a dendrite, afferents from the same functional ares will synapse in the same location so that if one fires, it can activate the others and give a grouped effect.
Give the classical steps of an AP at a chemical synapse
AP in presynaptic cell, DP of membrane in presynaptic axon terminal, Ca2+ enters, vesicle releases NT into synaptic cleft, transmitter binds to specific receptors on postsynaptic cell, transient change in conductance of postsynaptic cell to ions and transient change in membrane potential of postsynaptic cell [IF IONOTROPIC] ligand binds and activates g protein and second messenger system [IF METABOTROPIC]
How does the opening of voltage gated Ca2+ channels in the presynaptic terminal after an AP cause NT release?
Ca2+ entry activates calmodulin-kinase which phosphorylates synapsin-1 which causes NT release
How can we cause NT release with no AP?
Another NT may bind to the presynaptic terminal and allow Ca2+ to enter, AC may be activated which forms cAMP which activates PKC which phosphorylates synapsin-1 which causes NT release
How is Ach stored in vesicles?
VAChT protein
Name some proteins which are involved in the docking of Ach vesicles
SNAP-25, syntaxin, neurexins, calcium channels
What proteins can we measure as a marker for the degeneration of the brain in dementia and other disorders?
VGLUT-1 for Alzheimer’s or synaptophysin, a ubiquitous vesicle protein
How can neurotransmitters be terminated?
Metabolism to non-active compounds, reuptake into presynaptic terminal or glia
What are some biogenic neurotransmitters?
Ach, NA, Ad, DA, 5-AT
What are some amino acid neurotransmitters?
Glut, aspartate, GABA, glycine
What are some peptide neurotransmitters?
Somatostatin, endorphins, enkephalins, dynorphins, bradykinin, substance-P
What are some neurotransmitters which do not fit into any category?
NO, ATP, Adenosine
What affect does 5-HT1 have on AC?
Inhibits it
What affect does 5-HT2 have on PLC?
Activates it
What affect does 5-HT 4 or 6 or 7 have on AC?
Activates them
What effect does 5-HT3 have on synapses?
An iontropic effect
What is divergence?
Signals from multiple outputs can converge on neurones within a nucleus and be integrated to an output to an effector (/next level) controlled by interneurons
What is convergence?
When different presynaptic neurones send inputs to a single postsynaptic neurone which will fire or not depending on how many EPSPs and IPSPs there are
What drugs have effect on GABA?
Benzodiazepenes, anti-convulsants, anaesthetics
What drugs have effect on 5-HT?
Antidepressants, MAOI, tri-cyclines, SSRI, stimulants, MDMA, hallucinogens
What drugs have effect on NA?
Antidepressants, MAOI, tricyclics
What drugs have effect on DA?
Anti-Parksinson drugs, narcoleptics, stimulants (cocaine, amphetamine)
What drugs have an effect on peptide neurotransmission?
Analgesics
What drugs have an effect on glutamate?
Anti-ischaemia, anti-convulsants, cognitive enhancers
What drugs have an effect on Ach?
Anti-dementia
What are Merkel’s discs?
Slow light pressure and texture receptors
What do free nerve ending sense?
Warm, cold, itch and pain
What are Meissner’s corpuscles?
Quick, light touch receptors
Which receptor senses movement?
Hair follicle receptors
Which receptor senses vibration?
Pacinian’s corpuscle (quick)
What are Ruffini’s endings?
Slow receptors which sense stretch of the skin
What is a phasic response to a stimulus?
Adaptation to response that signals a change of state (e.g. hot to cold)
What is a tonic response to a stimulus?
Sustained response which usually encodes information about the status quo (e.g. it is still warm)
What produces the frequency and intensity of action potentials that constitute ‘the signal’?
Generator potentials in the sensory receptors
What produces generator potentials?
Changes in the behaviour of ion channels
What is the capsaicin receptor?
TRPV1
How are generator potentials produced for somatic sensations?
Non-specific cation channels that are opened by mechanical stress/ other sensory stimuli
What is the job of a generator potential?
Initiate AP at neuronal axon, modulate specific receptors, localised info on location of stimulus, graded info on intensity of stimulus
What is the job of a action potential?
Carry signal from point to point along axons, co-ordinated activity of voltage gated Na+ and K+ ion channels, versatile information coding, frequency and pattern coding
What kind of signal does a generator potential create?
A continuous, analogue signal which does decay
What kind of signal does an action potential create?
A digital signal which does not decay and passes long areas
Describe iontropic receptors
NT diffuses across synapse, bind to ion channels in post synaptic membrane causing them to open. These are non selective cation channels. DP occurs. Maximum depolarisation dictated by number and state of ion channels/receptors
What causes decline of the EPSP in synapses where glutamate acts at AMPA receptors?
Densensitisation of AMPA receptors
What causes decline of the EPSP in synapses where ACG acts at cholingeric receptors?
Destruction and recycling of Ach
What is an EPSP?
Excitatory post synaptic potential, a specialised generator potential
What is the job of an EPSP?
Synaptic potentials that contribute to somatic depolarisation leading to generate of an AP on the axon hillock of a neuron
What causes the decay of an EPSP?
Dissociation of the ligand, diffusion and uptake as well as desensitisation and enzymatic destruction
What changes the amplitude of an EPSP?
Number and state of receptors and amount of neurotransmitter released
What is a problem with EPSPs and IPSPs?
They are metabolically expensive and prone to chemical attack
What is an IPSP?
Inhibitory post synaptic potential, a specialised generator potential
What is the job of an IPSP?
Prevent somatic depolarisation and generation of AP at axon hillock
What speed are IPSP and EPSP?
Fast
How are fast IPSP’s generated?
Activation of ligand gated anion channels by GABA or glycine
What is the rostral or ventral part of the nervous system?
The anterior brain and superior spinal cord
What is the caudal or dorsal part of the nervous system?
The posterior brain and inferior spinal cord
What is in the central grey matter of the spinal cord?
Cell bodies
What is in the outer white matter of the spinal cord?
Axons and dendrites
What makes up the meninges?
Dura mater, arachnoid mater, pia mater
What spaces are created by the meninges?
Epidural, subdural and sub arachnoid
What are the ascending pathways of the nervous system?
Somatosensory systems or pathways through which sensory information from the periphery reaches the cerebral cortex
What are the tracts contained in the ascending pathways?
Dorsal column-medial lemniscal pathway, antero-lateral systems (spinothalamic tract) and spinocerebellar tracts
How is the grey matter of the spinal cord organised?
Into columns called the laminae of Rexed, numbered I-X
What information does the dorsal column-mediated lemniscal pathway carry?
Fine touch, vibration and proprioception via mechanoreceptors
What information does the spinothalamic (or antero-lateral) pathway carry?
Pain via nociceptors, temperature via thermoreceptors, crude touch via mechanoreceptors
What kind of pain does the spino-reticulothalamic pathway carry?
Dull aching pain
What information does the spinocerebellar pathway carry?
Proprioception and touch, awareness of where joints, skeletal muscles and tendons are in space
Describe the course of the first order neurones of the dorsal column-mediated lemniscal pathway
Carrying sensory information from touch or proprioceptive to the medulla oblongata via one of two pathways:
Signals from the upper limb travel in the lateral part of the dorsal column to the cuneate nucleus
Signals from the lower limb travel in the medial part of the dorsal column to the gracile nucleus
Describe the course of the second order neurones of the dorsal column-mediated lemniscal pathway
Beginning in either the cuneate or gracile nucleus, these neurones dessucate and travel in the contralateral medial lemiscus to reach the thalamus
Describe the course of the third order neurones of the dorsal column-mediated lemniscal pathway
Take the sensory signals from the thalamus to the brain. They travel from the ventral posterolateral nucleus of the thalamus, through the internal capsule and to the primary sensory cortex of the brain
Describe the course of the first order neurones of the spinothalamic pathway
Arise from sensory receptors and travel to the tip of the dorsal horn (substantia gelatinosa)
Describe the course of the second order neurones of the spinothalamic pathway
Travel from substantia gelatinosa to thalamus and dessucate. The neurones split into anterior and lateral conveyed crude touch and pressure and pain and temperature respectively
Describe the course of the third order neurones of the spinothalamic pathway
Carry information to S1 of the sensory cortex from the ventral posterolateral nucleus of the thalamus
What kind of fibres are in the spinothalamic pathway?
A-d fibres which are small and myelinated
What kind of fibres are in the spinoreticulothalamic pathway?
C-polymodal fibres which are unmyelinated
Describe the course of the spinoreticulothalamic pathway
1st order neurones synapse with 2nd in the posterior horn. The neurones dessucate and terminate in the medullary-potine reticular formation. 3rd order neurones synapse with the thalamus and 4th order neurones synapse diffusely to the entire cerebral cortex.
Which spinocerebellar pathways dessucate and which don’t?
Anterior does dessucate, posterior does not
What would be the effect of a lesion to the dorsal column?
Loss of fine touch, proprioception and vibration sensation. The damage will be ipslateral and below the lesion.
What would be the effect of a lesion to the medial lemniscus in the brainstem?
Loss of fine touch, proprioception and vibration sensation. The damage will be contralateral and below the lesion.
What would be the effect of a lesion to the spinothalamic tract?
Loss of crude touch, pain and temperature sense several segments below the lesion contralaterally
What is tabes dorsalis?
Tertiary syphilis in dorsal spinal roots and columns. Loss of proprioception so high step, unsteady gait and Romberg’s sign- worse with eyes shut, can fall over backwards
What can B12 deficiency cause?
Pernicious anaemia and degeneration of dorsal columns. Lateral columns- weakness and spasticity
What effect does MS have on the CNS?
Fasciculus cuneatus- loss of proprioception in hands and fingers. Loss of dexterity, inability to identify shape and nature of objects
What are the two divisions of descending pathways?
Pyramidal and extrapyramidal
Where does the pyramidal tract originate?
In the cerebral cortex
Where does the extrapyramidal tract originate?
In the brainstem
What does the pyramidal tract control?
Voluntary control of muscles of body and face
What does the extrapyramidal tract control?
Involuntary and autonomic control of musculature
Why are all neurones of the descending pathways classified as upper motor neurones?
There are no synapses in the descending system so all synapse onto lower motor neurones directly
Which are the pyramidal tracts?
Corticospinal and corticobulbar tracts
Which are the extrapyramidal tracts?
Vestibulospinal, reticulospinal, rubrospinal, tectospinal
What do corticospinal tracts control?
Musculature of body
What do corticobulbar tracts control?
Musculature of head and neck
Where do corticospinal tracts emerge and where do they receive info from?
Emerge in cerebral cortex and receive input from primary motor cortex, premotor cortex and supplementary motor area with input from somatosensory areas also
Do the fibres of the corticospinal tract dessucate?
The lateral tract does but the anterior tract does not
Where do fibres of the lateral corticospinal tract terminate?
Into the ventral horn of all segmental levels contralaterally
Where do fibres of the anterior corticospinal tract terminate?
Into the ventral horn of cervical and upper thoracic segmental levels ipslaterally
Where does the fibres of the corticobulbar tract arise?
Lateral aspect of the primary motor cortex
Do fibres of the corticobulbar tract dessucate?
No they all supply the face and neck bilaterally expect for the facial and hypoglossal nerves which give supply contralaterally
What is the function of the rubrospinal tract?
In general it excites flexor motor neurones and inhibits extensor motor neurones
Where does the rubrospinal tract originate?
The red nucleus of the midbrain
Are the fibres of the rubrospinal tract contralateral or ipslateral?
Contralateral
Where does the tectospinal tract originate?
In the superior colliculus of the midbrain
Where does the lateral reticulospinal tract originate?
Medullary reticular formation
Where does the vestibulospinal tract originate?
Vestibular nucleus
What is the function of the tectospinal tract?
Coordinates movements of the head to visual stimuli
What is the function of the reticulospinal tract?
Medial: facilitates voluntary movement, increases muscle tone
Lateral: inhibits voluntary movement, decreases muscle tone
Posture and balance
What is the function of the medial and lateral vestibulospinal tract?
Control balance and posture by innervating anti-gravity neurones (flexor of arm, extensor of leg) via lower motor neurones
Where does the medial reticulospinal tract originate?
Pons
How do reticulospinal fibres run?
Ipslaterally down the whole length of the spinal cord
What happens if there is a lesion to an upper motor neurone?
Spastic paralysis
What happens if the lesion to an upper motor neurone is above the point of dessucation?
Contralateral paralysis
What happens if the lesion to an upper motor neurone is below the point of dessucation?
Ipslateral paralysis
What is hypertonia?
Fixed position of limbs associated with upper motor neurone damage
What happens if there is a lesion to an lower motor neurone?
Flaccid paralysis, ipslateral to lesion level with hypotonia and atrophy
What is hyperreflexia?
Resistance to manipulation associated with upper motor neurone damage
What is Brown-Sequard syndrome?
Hemisection of the spinal cord leading to ipsilateral spastic paralysis and loss of fine touch, proprioception, vibration below lesion and contralateral loss of pain and temperature sense several segments below the lesion
What is syringomyelia?
Tubelike enlargement of the spinal cord leading to ipsilateral flaccid paralysis, weakness and atrophy of hand muscles and loss of pain and temperature sense bilaterally in arms and shoulders
What stimulates touch and via which receptors?
Mechanoreceptors sense skin motion/deformation
What stimulates proprioception and via which receptors?
Mechanoreceptors of joint and spindles sense muscle length and joint angle
What stimulates pain and via which receptors?
Noxious stimuli on thermo/chemo/mechanorecepots of all tissues except CNS
What stimulates itch and via which receptors?
Histamine acting on chemoreceptors of skin
What are the two classes of sensory neurones for face and body?
Dorsal root ganglion neurones for body, trigeminal sensory neurones for face
What properties can sensory receptors detect?
Modality- different receptors= different stimulus
Intensity- firing rate, no of receptors firing
Duration- firing duration
Location- receptive fields
What are the properties of Mesissner’s corpuscles?
Rapid acting and small receptive field
What are the properties of Merkel cells?
Slow acting, superficial
What are the properties of Pacinian corpuscles?
Rapid acting, deep, larger receptive field
What are the properties of Ruffini endings?
Slow acting, deep larger receptive field
What is the receptive field of a mechanoreceptor? Where can different receptive fields be found?
Spaital domain in which neurone can be excited or inhibited by stimulus. E.g. dense and small in finger tips for fine manipulation
What is the sensory function of muscle spindles?
Lie in parallel with main muscle fibres, sensitive to small changes in muscle length to regulate motor control of muscle length and help sense muscle position
What is the sensory function of Golgi Tendon Organs?
Lie in series with main muscle fibres and are sensitive to changes in muscle tension
What do nociceptors respond to?
Painful or damaging stimuli
What do thermoreceptors respond to?
Non-noxious hot or cold stimuli
Which type of neurones are sensitive to cold?
A-delta fibres
Which type of neurones are sensitive to warm?
C fibres
What are the properties of A-delta fibres?
Small, myelinated axons
What are the properties of C fibres?
Small, unmyelinated axons
What is the paradoxical response?
Firing of C fibres at really cold temperatures- burning sensation
How is mechanosensory information from the limbs and trunk carried?
Via dorsal columns and medial leminscal system to the VPL thalamus and cerebral cortex
How is mechanosensory information from the face carried?
Via trigeminal-thalamic system to VPM thalmus
What are dermatomes?
Areas of skin and deep tissue which are innervated by a single dorsal root ganglion.
What are the three divisions of the somatosensory cortex?
S1 primary, S2 secondary and posterior parietal
What are the subdivisions of the primary cortex?
Brodmann’s areas: 3a 3b, 1 and 2 of the postcentral gyrus
How are inputs of different modality into the somatosensory cortex organised?
Parallel processing into columns. Information of different types remains segregated
What information does Brodmann’s area 3b receive about an object?
Texture size and shape
What information does Brodmann’s area 1 receive about an object?
Texture
What information does Brodmann’s area 2 receive about an object?
Size and shape
What are the different receptive fields of Brodmann’s areas?
Neurones in areas 1 and 2 have much larger receptive fields than in 3b and different modalities converge
What is prosopagnosia?
Inability to recognise faces due to cortex damage
What is apraxia?
Defects in motor tasks
What is achromatopsia?
Defects in colour processing
What is akinetopsia?
Motion blindness. Defects in processing movement in the visual field
What separates motor and sensory cortexes?
Central sulcus
What is pure alexia?
Severe reading defects (not writing) caused by damage to the left visual cortex
How do areas of a homunculus relate to function?
Larger areas (typically hands, face) represent more motor/sensory importance
How do local circuits improve effciency of the CNS?
Can be autonomous of cortex, e.g. quick reflex response of turning toward light or sound
What do the swelling of the spinal cord at cervical and lumbar levels represent?
Due to inputs and outputs from limbs being at these levels means there is more grey matter
Which cranial nerves are in the hindbrain region? What do these do?
V-XII, muscle control and sensation of head
Which cranial nerves are in the midbrain region?
III, IV motor control of eye movement by visual and auditory cues (superior and inferior colliculi)
What does the hypothalamus integrate? Give examples of these functions
Autonomic and neuroendocrine systems for example circadian rhythms, metabolism, reproduction behaviour, body temp, defensive behaviour, BP and electrolytes
What is the dorsal diencephalon?
Hypothalamus
What is the ventral diencephalon?
Thalamus
What is the dorsal telecephalon in the adult?
Forebrain (cortex)
What is anencephaly?
Failure of head formation, incompatible with life
What is the ventral telecephalon in the adult?
Basal ganglia
What is craniorachischisis?
The most severe form of neural tube defect, a fully open spinal cord, incompatible with life
What is spina bifida?
Common spinal fusion defect, sac sticking out of infants back
What is spina bifida occulta?
Mild fusion defect ‘hidden’ spina bifida
What is spina bifida cystica?
Meningocele (meninges herniation) and meningomyelocele (spinal cord herniation)
How will a narrow dendritic spine neck affect a synpase?
Isolates synapse
How will a wide dendritic spine neck affect a synpase?
Allow easier flow
What is a graded potential?
Non-self renewing potentials along dendrites
What happens in MS?
Lose myelin, lose long range conduction (slowed down or prevented)
What is in the central white matter of the CNS?
Myelinated axons
What is in the outer grey matter of the CNS?
Cell bodies, dendrites, axons
Where are projection neurones?
Within cerebral hemispheres
Where are interneurones?
Within the CNS
What do oligodendrocytes do?
Myelinating cells of CNS, one can myelinate several axons
What do Schwann cells do?
Myelinating cells of PNS, one Schwann cell to one axon
What do microglia do?
Phagocytes of CNS
What do astrocytes do?
Link blood and brain through BBB, homeostasis of neurotransmitters, GABA and glutamate, and ions, repair- form glial scars, glycogen stores
What do ependymal cells do?
Produce CSF
What is the anterior blood supply of the brain?
2 x carotid arteries
What is the posterior blood supply of the brain?
2 x vertebral arteries
What forms the BBB?
Tight junctions and adherens junctions between epithelial cells with end feet of astrocytes wrapping around forming a perivascular feet
How can substances transverse the BBB?
Paracellularly, via transporters, passive diffusion, endocytosis
What makes up a tight junction?
Claudins 3,5, 12, occulins, junction adhesion molecule and endothelial selective adhesion molecule associating with peripheral membrane proteins like ZO1,2,3 anchoring actin to the cytoskeleton
What makes up a adherens junction?
Platlet-endothelial cell adhesion molecule, vascular endothelial cadherins
How does heroin get trapped in the CNS?
It crosses the BBB then is converted to morphine which cannot cross the BBB. This is how it leads to addictive behaviours
How do amino acids, nucleosides and glucose cross the BBB?
Specialised transporters, different for acidic, neutral and basic amino acids
What forms the blood CSF barrier?
The choroid plexus, apical tight junctions for filtration from blood to actively secrete CSF, synthesis polypeptides and regulate brain ECF and arachnoid mater
How is CSF secreted?
Transport of K+, Na+ and HCO3- into CSF, driving force for this is Na+K+ATPase pump maintaining low [Na+] in cells. Promotes 2ndary active transport of Na+, H+ and HCO3-, Cl-. K+, Cl- and HCO3- exit thru channels on apical membrane. Water follows ions through aquaporin-1
What are arachnoid granulations?
Valve like structures in the superior saggittal sinus, CSF flows into venous blood here
What are the circumventricular organs?
Highly vascularised structures in the CNS which have no BBB and link CNS to PNS
Which are the sensory circumventricular organs?
Area postrema, subcommisural organ, subfornical organ, vascular organ of the lamina terminalis
Which are the neurohaemal secretory type circumventricular organs?
Median eminence, neurohypophysis, pineal gland, choroid plexus
