BIOL2230 - Neurophysiology

Describe the major divisions of the nervous system

CNS and PNS

PNS: sensory and motor

Sensory: somatic, visceral and special receptors

Motor: somatic, autonomic and enteric

Describe the functional organisation of the spinal nerves

Motor and sensory nerves leave the spinal cord and bundle together into fascicles

Fascicles contain multiple axons and are surrounded by connective tissue

Each spinal nerve contains multiple fascicles

Describe the structure of the cerebral cortex

It contains 6 cortical columns

The left brain processes the right side of the body and vice versa

It contains pyramidal (large dendritic trees, long axon for communication outside cerebral cortex) and stellate neurons (short dendritic trees, short axon for communication inside cerebral cortex)

What are the three types of white matter in the brain?

Commissural: connects the left and right hemispheres

Association: connects areas of one hemisphere

Projection: travel to and from the cortex via the brainstem

Describe the anatomy and function of the thalamus

Anatomy: symmetrical, made of multiple nuclei

Function: relays motor information, regulates consciousness, sleep and alertness

What are the structures that make up the limbic system?

Hippocampus, amygdala, cingulate gyrus, parahippocampal gyrus

Thalamus, hypothalamus

What are the structures that make up the brainstem?

Midbrain

Pons

Medulla oblongata

Describe the function of the pons

Sleep, bladder control, respiration, hearing, balance, posture, eye movements, taste, swallowing, facial expression/sensation

Also contains pontine respiratory centre for voluntary control and adjustment of breathing

Describe the function of the medulla oblongata

Receives information from chemoreceptors, interacts with motor nerves and pontine respiratory centre to control breathing

Also controls cardiovascular system

What are the principles of equimolality and electrical neutrality?

Equimolality: the concentrations of ions in the ICF and ECF must be equal

Electrical neutrality: the ICF and ECF anions must balance, and the ICF and ECF cations must balance

What does the Nernst equation find?

The equilibrium potential of a certain ion, given its valence and concentration within and without the cell

Describe the characteristics of a graded potential

Small, rapid VM changes

Irregular size

Spreads electrotonically

Fast

Dissipates at an exponential rate

Strength and duration is proportional to stimulus strength

Susceptible to noise

Depolarising or hyperpolarising

Describe the characteristics of an action potential

Large VM changes

Regular

Spread slowly

Long distance, can regenerate

Frequency codes stimulus strength

Not affected by noise

Only depolarising

Frequency: ~5-100Hz

Pulse length: 1-400ms

Conduction velocity: 1-120m/s

What are the advantages and disadvantages of each electrophysiological recording type?

Extracellular

+ Easy to do

- Small signal which dissipates

- Signal is local field potential

Intracellular

+ Measures one cell

- Invasive, harder to do

Patch clamp

+ Measures one ion channel

+ Can compare activity of different neuron parts

- Very hard to do

What are the major categories of neurotransmitters?

Classical: single amino acids, biogenic monoamines, ACh

Neuropeptides

Purines

Others

Compare electrical and chemical synapses

Electrical:

Rapid

Unidirectional or bidirectional

Excitatory or inhibitory

Sign-conserving

Chemical:

Slower

Unidirectional

Excitatory (Type I) or inhibitory (Type II)

Not sign-conserving

Describe direct coupling

NT binds to GPCR, which activates alpha-subunit that acts as a ligand for an ion channel

Describe indirect coupling

NT binds to GCPR, which activates alpha-subunit which activates/inhibits an enzyme. The enzyme activates a secondary messenger that opens/closes an ion channel.

What are post-synaptic potentials?

Small, temporary changes in membrane potential as a result of a neurotransmitter binding

What is modality of a sensory receptor?

The form of energy of a stimulus; the adequate stimulus is the modality a receptor responds best to

What are the functional categories of sensory neurons?

Exteroceptors (external): mechanoreceptors, photoreceptors, chemoreceptors, thermoreceptors

Interoceptors (internal): chemoreceptors, baroreceptors, osmoreceptors

Proprioceptors (posture, position): a type of mechanoreceptors

What are the structural categories of sensory neurons?

Simple: dendrites are sensory receptors

Complex: connective tissue surrounds dendrites

Special senses: receptor cell synapses onto dendrites

Where is the trigger zone in pseudo-unipolar cells?

Where the axon meets the dendrites, so that GPs generated here can be converted to an AP

Distinguish between phasic and tonic receptors

Phasic: quickly adapt

Tonic: slowly adapt

What factors determine acuity?

Receptive field of sensory units

Density

Overlap of receptive fields

Convergence

Lateral inhibition

What are the overall properties of cutaneous mechanoreceptors?

Detect touch, pressure, vibration and stretch

Low threshold (high sensitivity)

Signal with glutamate

Mostly A-beta (large, myelinated)

Describe hair follicle receptors

RA1: rapidly adapting, small receptive field

Detect bending of hairs in response to air movement or touch

Only present in hairy skin

Wrapped around base of hair follicle

Free nerve endings

Describe the properties of thermoreceptors

Free nerve endings in superficial layers of skin

RA2

Population coding (activity of receptors with different ranges compared)

Signal when temperature changes

Which neurons use the spinothalamic vs. DCML tracts?

Spinothalamic: nociceptors, thermoreceptors, mechanoreceptors

DCML: mechanoreceptors, proprioceptors

Describe the trigeminothalamic pathway

1. Trigeminal nerve from face to nuclei in brainstem and spinal cord

2. To Thalamus

3. To somatosensory cortex

Describe the primary somatosensory cortex

Postcentral gyrus

Determines stimulus type, intensity and location

Describe the secondary somatosensory cortex

Upper lip of lateral sulcus

Higher order processing

Integrates sensory and motor information

Integrates information from both body sides

Integrates with limbic system for learning and memory

Describe the somatosensory association area

Posterior parietal cortex

Receives input from both somatosensory cortices

Integrates visual and sensory input

Coordinates motor response

What are some causes of neuropathic pain?

Lesion

Disease/infection

Compression/pinching/trauma of nerves

Inflammation

Damage to ion channels

Describe the properties of nociceptors

Free nerve endings

Mechanoreceptors, thermoreceptors, chemoreceptors or polymodal

No background firing

Large receptive fields

High threshold

Tonic

Signal using glutamate and substance P

Define and describe inflammatory soup

Tissue damage causes the release of:

ATP, ions, prostaglandin, Substance P

Bradykinin

Serotonin

Histamine

This impacts pain perception by nociceptors

Describe the pathway of nociceptive perception to the brain

1: nociceptor activated and synapses onto dorsal horn using glutamate and Substance P

2: decussate at spinal cord, then to thalamus

3: to somatosensory cortex

Signals also sent to limbic system for emotional/behavioural response

How does the limbic system cause descending pain pathways?

It sends efferent pathways via the spinal cord to the dorsal horn

Either excitatory (serotonin onto nociceptor) or inhibitory (noradrenaline, steroids or opioids released onto other receptors)

How do interneuron suppress pain?

Interneurons release endogenous opioids onto first-order neurons to inhibit Substance P release

Or onto secondary neurons to cause inhibitory post-synaptic potentials

Define pain sensitisation and its types

Sensitisation: increased sensitivity to pain

Hyperalgesia: more pain than normal

Allodynia: pain from a non-painful stimulus

What is the gate-control theory of pain?

Mechanical stimulation of A-beta fibres (cutaneous mechanoreceptors) activate inhibitory interneurons (using GABA or glycine) to inhibit C-fibres

Describe the structure of the olfactory epithelium

2 layers

Olfactory mucosa: receptor cells, basal replacement cells

Lamina propria: connective tissue, mucus-secreting cells

Describe the structure of olfactory chemoreceptors

Bipolar cells

Dendrites in olfactory mucosa for reception

Dendrites are olfactory knobs containing cilia

High sensitivity

Receptive to one chemical each

Explain olfactory transduction

Chemical binds to G-protein coupled receptor

G(olf) protein activates adenylyl cyclase

ATP converted into cAMP

cAMP opens cation channels (depolarisation)

Ca2+ opens Cl- channels (more depolarisation)

GP generated, generating AP

Glutamate released onto 2ndary neurons

Explain how olfactory information is processed in the brain

Mitral and tufted cells project to olfactory/piriform cortex located in the temporal lobe

Activation of different receptor types compared (population coding)

Entorhinal cortex then travels to thalamus for relay elsewhere

Explain how sweet signalling occurs

Sweet tastant opens G-protein coupled receptor

G-protein activates adenylate cyclase

ATP converted to cAMP

cAMP activates a protein kinase that closes K+ channels (depolarisation and NT release)

Explain how gustatory information is processed in the brain

Three cranial nerves involved: 7, 9 and 10

1: cranial nerves travel to gustatory nucleus in medulla

2: to thalamus

3: to primary gustatory cortex in insula lobe

Compare Type II and Type III cells in taste buds

Type II: bitter, umami and sweet, signals using ATP with no clear synapse (may activate Type III)

Type III: sour and salty, signals using serotonin (may inhibit Type II)

Describe the structure of the organ of corti

Contains inner and outer hair cells

Outer hair cells have stereocilia embedded in the tectorial membrane, which is connected to the basilar membrane

When endolymph moves, this moves the tectorial membrane and activates OHCs

When the endolymph moves, this directly activates IHCs

No kinocilium in the organ of corti stereocilia!!!

Compare the ion concentrations of the endolymph and perilymph

Perilymph: low K+, high Na+

Endolymph: high K+, low Na+ (electrochemical force driving K+ in when channels open)

Describe the pathway of auditory information to the brain

Travels via CN 8 to brainstem, then thalamus, then primary auditory cortex

What is the structural organisation of the primary auditory cortex?

Arranged by frequency

Name each of the cranial nerves and their function

1: olfactory

2: optic

3, 4, 6: eye movement

5: trigeminal

8: vestibular, auditory

10: vagus

Describe the pathway of vestibular information to the brain

Vestibular nerve (CNVIII) synapses onto vestibular nucleus

To cerebellum, vestibular cortex and eye muscle cranial nerve nuclei

Describe the vestibuloocular reflex

Receives information from semicircular canals (endolymph movement) and proprioception

CNVIII signals to nuclei of cranial nerves to cause eye movement in opposite direction to head

Describe the vestibulospinal reflex

Receives information from otolith organs

CNVIII signals to vestibular nuclei in brainstem

To spinal cord, then motor neurons

Describe the vestibular cortices in the brain

Parietoinsular vestibular cortex processes spatial orientation and movement

Multimodal association area integrates vestibular information with vision and proprioception

Describe the structure of the photoreceptor outer segment

A stack of discs

Visual pigment molecules (VPMs) are embedded in the membrane of discs

Contain opsin and chromaphore

Compare rods and cones

Rods:

More common

Night vision

High sensitivity

Saturate quickly

Long, conical

Cones:

Less common

Colour vision

Low sensitivity

Saturate slowly

Short, tapered

Detect movement well

Describe the general structure of a photoreceptor

Outer segment for transduction

Inner segment containing nucleus

Synaptic terminals

Explain the process of photoisomerisation and phototransduction

Light isomerises chromophore

Conformational change of opsin

Transducin activated

PDE activated by transducin alpha-subunit

cGMP broken down by PDE

Describe photoreceptor activity during dark

High cGMP levels

cGMP Na+ channels opened

Cell depolarised

VGCCs open

Glutamate release

Describe photoreceptor activity during light

Low cGMP levels

cGMP Na+ channels close

Cell hyperpolarised

No glutamate release

Describe the visual processing function of retinal bipolar cells

Temporal processing

Describe the visual processing function of retinal ganglion cells

Determine basic features of the image (brightness, colour, motion, uniformity, edge detection)

Describe the pathway of visual information in the brain

Optic nerves cross over at optic chiasm

Synapse at lateral geniculate nucleus

Neurons project to primary visual cortex

What sites does the myosin globular head contain?

Actin-binding and myosin ATPase

What properties make an NMJ different from a chemical synapse?

Only excitatory

ACh is used

Motor endplate is folded

Motor endplate contains nicotinic ACh receptors

1 AP causes 1 muscle twitch

AChE removes ACh from synaptic cleft

Describe the structure of voltage-gated calcium channels in myocytes

DHP receptor (conformationally changed by depolarisation)

Ryanodine receptor (opened by change in DHP)

Describe the four stages of increasing muscle tension

Treppe: full relaxation, increasing tension until plateau

Wave summation: partial relaxation, overlap of twitches, Ca2+ released faster than removed

Unfused tetanus: brief, partial relaxation, troponin-tropomyosin saturated by Ca2+, all myosin-binding sites on actin exposed

Fused tetanus: no relaxation, maximal contraction, continual exposure of actin

Describe the factors affecting muscle tension

Stimulation frequency

Fibre diameter

Fibre length at start of contraction

Fatigue

Compare ATP hydrolysis of fast and slow-twitch muscle

Fast: glycolysis

Slow: oxidative phosphorylation

Compare skeletal, cardiac and smooth muscle

Skeletal: striated, voluntary, multi-nucleated, only excitatory, Ca2+ from SR, troponin-tropomyosin, NMJ

Cardiac: striated, involuntary, 1-2 nuclei, longer APs for no overlap of contraction, Ca2+ from ECF and SR, troponin-tropomyosin, NEJ

Smooth: non-striated, involuntary, 1 nucleus, excitatory or inhibitory, Ca2+ from ECF and SR, calmodulin, NEJ

What are the three ways of classifying smooth muscle?

Neurogenic (requires neural stimulation) vs. myogenic (capable of initiating contraction)

Phasic (bursts of contraction) vs. tonic (continuous contraction, regulated by [Ca2+])

Multi-unit (neurogenic, tonic) vs. single-unit (myogenic, phasic)

What causes Mysathenia Gravis and Lambert-Eaton Syndrome?

Autoimmune diseases, where immune cells target parts of the neurons

What receptors does ACh bind to on the motor end plate?

Nicotinic acetylcholine receptors

Compare upper and lower motor neurons

UMNs: connect motor cortex (voluntary) or brainstem (involuntary) to LMNs directly/indirectly

LMNs: originate in cranial nerve nuclei (involuntary) or ventral horn (voluntary) and innervate muscle

Compare the two types of LMNs

Alpha: large diameter, myelinated, innervate extrafusal fibre (for movement)

Gamma: smaller diameter, myelinated, innervate intrafusal fibre (for proprioception)

Describe the Renshaw loop

LMN excites muscle and also releases ACh onto Renshaw cells

Renshaw cells are inhibitory interneurons next to alpha LMNs and provide negative feedback to prevent overactivation

Describe how LMNs integrate sensory and motor information to form the final common pathway

LMNs receive +/- input from UMNs, sensory feedback from spindle fibres and interneurons

The effects of these are summed and may/may not cause an AP

This is important since NMJs are only excitatory, so if an AP is generated, a twitch will occur

Compare small and large motor units

Small: in small muscles (e.g., eyes), small increase in force, precise, smaller diameter fibres, slower fatigue

Large: in large muscles (e.g., quads), large increases in force, less precise, larger diameter fibres, faster fatigue

Large motor units have larger cell bodies, more leak channels and are harder to depolarise

What proprioceptors are present in muscle?

Muscle spindles: muscle length

Golgi tendon receptors: muscle tension

Describe how muscle spindles detect muscle length changes

Part of intrafusal fibre

Innervated by afferent signals (stretch receptors; Type 1a and 2) and efferent signals (gamma LMN)

Always some depolarisation for low-level muscle activation

Muscle stretch causes depolarisation and increased firing

This causes alpha LMN to counteract it and contract (and opposite occurs when muscle contracts and afferents are hyperpolarised)

What is the difference between Type 1a and 2 stretch receptors?

1a: primary endings wrapped around muscle to detect muscle stretch

2: secondary/flower spray endings to detect muscle length

What are the four categories used to classify reflexes?

Level of processing: cranial/spinal

Somatic/autonomic

Innate/conditioned (e.g., Pavlov's dog)

Monosynaptic/polysynaptic

What are the properties of stretch reflexes?

Stimulus: spindle fibre stretch

Response: contraction to counteract stretch

Somatic reflex

Describe the Golgi tendon reflex

Stimulus: stretch of Golgi tendon

Integrator: spinal cord (disynaptic), excitatory to hamstring, inhibitory to quads

Response: hamstring contraction, quads relaxation

Describe the withdrawal and crossed-extensor reflex

Stimulus: nociceptor activation in leg

Response: afferent neuron synapses onto 5 other neurons: one to excite the hamstring, one to inhibit the quads (this withdraws the leg), one to excite the quads and one to inhibit the hamstring (to stabilise the other leg), and one to decussate and travel to the brain

Describe the main areas of the motor cortex

Primary: pre-central sulcus, UMNs originate

Premotor: in front of M1, coordinates voluntary movement

Prefrontal association areas: front of brain, plans voluntary movement, thoughts and personality

Describe the structure and neurons of the motor cortex

Arranged somatotropically

Contain pyramidal neurons (UMNs) which synapse onto interneurons

Also contain Betz cells, pyramidal neurons which synapse directly onto LMNs for precise movements

Compare the pyramidal and extrapyramidal tracts

Pyramidal: voluntary, originate in motor cortex, either corticospinal or corticobulbar, decussate at medulla

Extrapyramidal: voluntary and involuntary, originate in brainstem nuclei, simple movement

Describe the corticospinal tract

UMNs originate in cerebral cortex (either frontal or parietal lobe)

Fibres travel through brainstem to medullary pyramids

Some decussate here, forming the lateral tract for arm, hand movements

Others decussate at the end of the spinal cord, forming the anterior tract for balance, posture

Describe the corticobulbar tract

UMNs travel from motor cortex to synapse onto:

LMNs in cranial nerve nuclei

Or interneurons that project to LMNs

Describe the inputs and output of the cerebellum

Inputs:

Mossy fibres from brainstem and spinal cord, synapse onto granule cells

Climbing fibres from inferior olive, synapse onto Purkinje cells

Both provide sensory and motor information

Purkinje cells then synapse from cerebellar cortex to deep nuclei

Output: deep nuclei which affect movement

Describe the inputs and outputs of the basal ganglia

Inputs: motor information from cerebral cortex to striatum first, then other basal ganglia

Outputs: return to cerebral cortex via thalamus, then travel via pyramidal pathways

Describe how the basal ganglia inhibits/excites movement

Globus pallidus interna normally inhibits the thalamus

Direct pathway: for movement, the striatum inhibits GPi to excite movement

Indirect pathway: for no movement, the striatum excites GPi to inhibit movement

What neurotransmitters control the direct and indirect pathways?

Substantia nigra: dopamine excites direct and inhibits indirect pathway

Striatum interneurons: ACh inhibits direct and excites indirect pathway

Describe the main symptoms of dementia

Memory impairment, executive dysfunction, impaired communication, impaired recognition, personality

Describe the causes and symptoms of Alzheimer's disease

Cause:

Beta amyloid plaques (EC)

Neurofibrillary tangles of tau protein (IC)

Neurophysiology: frontal lobes and hippocampus

Symptoms: dementia

Describe the causes and symptoms of Parkinson's disease

Cause: Lewy bodies (aggregates of alpha-synuclein)

Neurophysiology: substantia nigra (excites movement)

Symptoms: hypokinetic movment disorder (loss of movement)