01 Neurophysiology Flashcards
Active Transport
ATP protein pump needed to transfer across membrane.
Diffusion
The movement of solute from an area of higher concentration to an area of lower concentration
Facilitated Diffusion
Passive process where a facilitator (channel protein) is needed. Eg. Ions
Equilibrium Potential
When [] Gradient = electric repulsion
Different for K and Na.
Ek = -90mV
ENa = +60mV
Resting membrane potential (RMP)
~ -70mV
Established by the Na+/K+ATPase.
Need selectively permeable membrane and [ion] difference between inside/outside of cell.
Depolarization
More positive (+)
- Open more Na+ channels (INward gradient)
- Decrease #K+ channels open
Generator Potential
Electrical event generated by stimuli. If large enough will produce an AP.
GRADED - vary in size (amplitude): larger stimulus will generate larger depolarization
What is the role of a Na+/K+ATPase in the generation and maintenance of a RMP?
ONLY MOVES IONS. Selectively permeable membrane separates charges. ATPase regulates the [K+] and [Na+] inside and outside the cell which affects equilibrium potential.
What is the [K+] inside and outside the cell? Which direction does the gradient favour?
Inside: [150mM]
Outside: [5mM]
Gradient is OUTward
Always tries to push Vm to Ek (-90mV)
What is the [Na+] inside and outside the cell? Which direction does the gradient favour?
Inside: [15mM]
Outside: [150mM]
Gradient is INward
Always tries to push Vm to ENa (+60mV)
At rest, why is RMP closer to Ek?
At rest, more K+ channels are open so the RMP is closer to the Ek value (-90mV)
Action potential (AP)
All or nothing electrical event triggered when membrane potential reaches threshold.
What are the components of Axonal Action Potential? (Think about the graph)
Threshold: AP elicited by suprathreshold (more than threshold) or threshold stimuli
Rising Phase: Rapid depolarization of the membrane caused by increased permeability of Na+ (PNa+)
Falling Phase: Rapid return to RMP because of increased K+ permeability (PK+)
After Hyperpolarization: Vm is closer to Ek than at rest because K+ channels are open and gK (change in conductance - movement of charged ions - of K+ ions) is greater than at rest.
Explain the role of voltage-gated Na+ and K+ channels in the generation of an axonal AP. (Think of images. Slide 36)
Na: Activation gate & Inactivation gate
K: Activation gate
Voltage-gated channels have a voltage sensors (AA with charged residues) that moves in response to membrane voltage changes. This movement is coupled to the activation gate.
Depolarization: Activation gate probably open. Inactivation gate probably closed.
How is action potential a REGENERATIVE EVENT?
Positive feedback depolarization?
AP in one part of the membrane will initiate an AP in a more distant part of the cell
Depolarization opens SOME voltage-gated Na+ channels and the influx of Na+ further decreases the membrane potential and recruits neighbouring channels (opens them)
Absolute Refractoriness
Inactive Na+ channels ensures that signals only go one way. A second stimulus will not do anything yet.
Relative Refractoriness
When AP closer to being fully recovered, we can generate a second AP by using a more intense stimulus. Why? because some channels have not recovered from inactivation yet (fewer channels available)
What is the mechanism of depolarization block of AP firing?
Some Na+ channels are inactivated (Inactivation gate closed) and cannot conduct current.
Recovery from inactivation opens Na+ inactivation gate (Channel available again) and closes K+ activation gate (return Vm to RMP)
Electrotonus
Newton’s cradle.
Process by which electrical events propagate - Movement of positive charge axially.
[Analogy]: Water in a hose
- Current enters axon through ion channels in a region of membrane and depolarizes that region.
- Intracellular (+) charge attracted to adjacent (-) charged regions of membrane
- Electrotonic spread of current (passive process)
Electrotonic Decay & Length Constant
Electrotonic Decay: As a current travels through the axon, charge leaks outward across the membrane. (Leakiness)
Length Constant: distance a passive electrical event can propagate along a neuronal process. (How long it travels before leaking to nothing)
Active Propagation of Electrical Potentials
Regenerative process where APs activate voltage-gated channels along axonal membrane to REGENERATE the depolarization. (Combats leakiness)
Voltage-gated channels BOOST and regenerates inward current and counteracts outward current leak.
What factors influence the active propagation of an AP along an axon?
- Diameter of the fibre: Increase diameter = decreased Ra (Axial resistance)
- Amount of membrane capacitance: Less membrane capacitance = greater rate of AP propagation.
Resistance
Rm - resistance of membrane
Ra - axial resistance
Resistors can change voltage instantly.
Capacitor
Two conducting plates separated by an insulating layer. Has the ability to STORE electrical charge. Takes time to change charge on capacitors. Resistors can change voltage instantly.
Capacitance
Thick capacitor = lower capacitance.
Thin capacitor = higher capacitance.
Capacitance = “Resistance”
[Analogy]: (+) and (-) charge separated by more distance = easier to move the charge (Less “resistance”)
What is the role of Myelin in AP propagation?
Myelin is formed from Schwann cells in PNS and Oligodendrocytes in CNS.
Myeline decreases capacitance and AP propagates faster in myelinated areas. Increases Rm, Decreases Ra.
What is Saltatory Conduction?
Propagation of AP from one Node of Ranvier to the next.
AP goes FAST and then SLOW. FAST slow FAST slow
{Latin} Saltare: hop or leap
Describe EXCITATORY synaptic transmission in the CNS mediated by GLUTAMATE.
Glutamate = excitatory neurotransmitter
May act on may receptor subtypes (AMPA, NMDA)
- AMPA-gated channels allow (2) BOTH Na+/K+ ions through open pore - Generates EPSP with EQ potential of ~0mV. Brings postsynaptic neuron closer to AP threshold.
- NMDA-gated channels are permable to (3) Na+, K+ & Ca2+ ions - Gating requires a DEPOLARIZATION coincident with glutamate binding. (excitatory) Ca2+ entry influences intracellular metabolic processes.
Describe INHIBITORY synaptic transmission in the CNS mediated by GABA.
Inhibitory neutrotransmitters bind receptors that generate PSPs that keep Vm from reaching AP threshold (IPSP). In CNS, a common inhibitory neurotransmitter is GABA.
GABA_A allows the entry of Cl- through an open pore which changes Vm to -70mV (ECl) - also RMP in some cells
Synapses
End of a neuron where neurotransmitters hop from one place to another. Axon terminal to dendrite
What are the steps of Synaptic Transmission?
- AP propagation in presynaptic neuron
- Ca2+ entry into synaptic knob
Ca2+ causes things to turn on/off. Moves vescicles to synaptic membrane > subsynaptic membrane. - Release of neurotransmitter by exocytosis
- Binding of neurotransmitter to postsynaptic receptor
- Opening of specific ion channels in subsynaptic membrane.
Slide 65 W1
Synaptic Current (Isyn)
Binding of neurotransmitter to an extracellular receptor on a postsynaptic ion channel induces conformational change of channel - opening channel pore.
Resulting ION MOVEMENT through the pore in POSTSYNAPTIC cell membrane generates Isyn (Synaptic current).
Postsynaptic Potential (PSP)
The change in Vm generated by Isyn
Either stays the same, depolarized or hyperpolarized
Excitatory Postsynaptic Potential (EPSP)
DEPOLARIZING PSPs generated by receptors binded to EXCITATORY neurotransmitters which bring Vm CLOSER to AP threshold.
Nick: EPSP is like a GP. GP is made by stimuli, EPSP is made by a synapse.
Neurotransmitter Gated Ion Channel
Acetylcholine binding causes conformational change and opens channel allowing ions to move across the membrane. Only allows one ion in channel at any given time.
Selects for X+. Doesn’t care if it’s K+ or Na+ just wants a monovalent cation.
Moves Vm to -15mV (Middle of Ek and ENa)
Why is there Dendritic Summation of EPSPs?
EPSP’s decrease in amplitude while traveling towards the soma. A single EPSP will not bring neuron to AP threshold. EPSPs SUMMATE (to overcome leaks) to cause AP firing in postsynaptic neuron.
Temporal Summation
Involves REPETITIVE activation of a single synapse.
Frequency is important. EPSPs add together
Large compound EPSP results - may reach AP threshold
Spatial Summation
Involves SIMULTANEOUS activation of multiple synapses.
Large compound EPSP results - may reach AP threshold
Identify the neuronal components of the Peripheral Nervous System (PNS). What are the neurotransmistter and receptor types used?
Motor Neurones (Efferent): Cell body in CNS
Innervate striated muscle cells
Release ACh
Receptor: Nicotinic receptors at neuromuscular junction (NMJ)
Ipsilateral: L to L / R to R
Contralateral: L to R / R to L
Sensory Neurones (Afferent): Cell body outside CNS in sensory ganglia
Autonomic Neurones: Always working in the background
In the PNS and are either Sympathetic or Parasympathetic: Have 2 neurons in the pathway from the CNS to the peripheral organ.
1) Preganglionic - Cell body in CNS
2) Postganglionic - Autonomic ganglion in the periphery
Ganglion is close to or actually inside target organ in parasympathetic system. ?
Identify the neuronal components of the Autonomic Nervous System (ANS). What are the neurotransmitter and receptor types used?
Reflexes: Spinal cord level
Medulla: Most reflexes here (within brainstem)
Hypothalmus
Prefrontal Cortex: Emotional states (Eg. Is it appropriate to pee here?)
ANS Afferents:
Baroreceptors - blood pressure
Osmoreceptors - plasma ion concentration (Need more salt? Eat more salt)
Thermal sensors - regulate body temperature
Cutaneous receptors - sexual stimuli
Stretch receptors - distention in lungs, bladder, stomach, bowel
Specifically identify and name the function of each cranial nerve.
I Olfactory (On) - Nose II Optic (On) - Eyes (Vision) III Oculomotor (On) - PARASYMPATHETIC - Move eyes IV Trochlear (They) - Eye muscle V Trigeminal (Traveled) - Face VI Abducens (And) - Moves eyeballs laterally VII Facial (Found) - PARASYMPATHETIC - Facial expression and sailvary glands (Taste) VIII Vestibulocochlear (Voldemort) - Hearing and Balance IX Glossopharyngeal (Guarding) - PARASYMPATHETIC - Swallowing (Taste), eyes, salivary, heart, GI tract X Vagus (Very) - PARASYMPATHETIC - Swallowing XI Accessory (Ancient) - Swallowing, shoulder shrugging XII Hypoglossal (Horcruxes) - Tongue
Identify and understand the organisation of the spinal nerves in relation to levels of the spinal cord.
Cervical (8) - C1 to C8 Thoracic (12) - T1 to T12 - Sympathetic output Lumbar (5) - L1 to L5 Sacral (5) - S1 to S5 - Parasympathetic Coccygeal (1)
Describe the cranial, thoracic and sacral outflow of ANS nerves
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Identify the pharmacological differences between the Sympathetic and Parasympathetic systems.
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Describe the general functions of Sympathetic and Parasympathetic systems on the body.
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Special Senses
Modalities carried by cranial nerves:
Olfaction (smell), Vision, Taste, Hearing and balance
General (Somatic) Senses
Touch, pressure, temperature, pain.
Detected from all parts of the body + head and transmitted to CNS via Trigeminal (V) and all spinal nerves except C1.
What are the Catabolic Effects of the Sympathetic Nervous System?
Increased heart rate, stroke volume, blood pressure
Increased blood flow to skeletal muscle.
Decreased blood flow to skin
FIGHT or FLIGHT response: Release of epinephrine/norepinephrine from adrenal medulla > skeletal muscle glycogenolysis.
What are the Anabolic Effects of the Parasympathetic Nervous System?
Decreased heart rate, stroke volume, blood pressure
Increased GI tract motility/secretions.
Relaxation of sphincters in esophagus, stomach, bladder
Paradoxical Co-activation
Both sympathetic and parasympathetic systems activated during intense conflict situations
Transducers
All sensory systems have a transducer - convert all different types of input into APs (Electrical event).
Convert one form of energy into another form.
Detect various stimuli and convert them into APs.
Eg. Sensory Receptors:
Photoreceptors - light: rods/cones of retina
Thermoreceptors - changes in temperature,
Nociceptors - pain
*Mechanoreceptors - mechanical stimuli
a) Exteroceptors - respond to stimuli from outside body
b) Proprioceptors - inside body (info about position of body or its parts)
Generator Potential (Sensory)
Usually Depolarization in a sensory system caused by SENSORY stimulus.
Except: Visual system which has a hyperpolarizing GP.
1st node of Ranvier is where the AP is initated.
Different types of Sensory Receptors?
a) Voltage-gated channels: Receptor physically attached to the cell - activated by stimulus + depolarization propagation
b) Chemical messenger-gated channels: Receptor connected to neuron via chemical messenger - diffuses to neuron from receptor to activate (indirect)
Compare and contrast a GP and EPSP
SAME: Both transient depolarizations Both happen because of ion channel open Both GRADED (Various amplitudes) Not actively propagated like an AP Do not have a refractory membrane. (Refractoriness only happens in axon actively propagating an AP region behind)
GP: Happens in the sensory tranducer, sensory receptor.
EPSP: Happens in a SYNAPSE between two neurons
Mechanoreceptors
Cytoskeletal network anchors channel in place and are physically opened.
Every sensory input will open a channel!
SENSORY CODING: How is stimulus intensity coded? How do we know how much force is being exerted on us etc?
a) Frequency Coding: Change in frequency is not linear.
Greater intensity = Greater frequency of APs in each axon.
Frequency changed when information changes.
b) Population Coding: More neurons are recruited.
Bigger stimulus = Larger number of neurons carrying information.
How do sensory receptors adapt?
a) Tonic - Slowly Adapting: Monitor static unchanging stimuli Maintained stimulus and AP firing. Eg. Maintained muscle length (Secondary endings of muscle spindle) Maintained pressure (Ruffini endings of skin)
b) Phasic - Rapidly Adapting: Tell you when a stimulus starts/stops. Only detects ON/OFF response.
Eg. Change in time - vibration (Pacinian corpuscle)
Change in space (Meissner’s corpuscle in the skin)
Pacinian Corpuscle
Define and describe how it works.
Rapidly adapting cutaneous (skin) mechanoreceptor
Detects movement/pressure changes in skin.
Accessory structure not part of neuron with fluid in between connective tissue layers. Force transfered downward through layers of PC until it reaches the axon and then force travels laterally through axon.
Sensory receptors responding to having Clothing on your skin?
Rapidly adapting - feel when you put the clothes on
Slowly adaptig - don’t adapt. keeps telling you theres a shirt there but you ignore the information (unimportant) - consciously adapt.
Unless itchy.
Tactile (Touch) Receptors
a) Meissner’s Corpuscles (for fine discriminative ability in fingers, lips etc) & Pacinian corpuscles - rapidly adapting, involved in discriminative touch
b) Merkel’s endings & Ruffini endings - in less discriminatory areas. Slowly adapting. Eg. your back - less info needed.
Signal non-changing features of tactile stimuli.
What we really need to understand:
There are rapid/slow receptors
Tell us about changing/maintained stimuli
Pacinian corpuscle = rapidly adapting.
Receptors for Proprioception
Give internal information
a) Muscle spindle - stretch reflex and length receptors - you know where your limbs are + map out your body.
b) Golgi Tendon Organs - tension receptors
c) Joint receptors - Ruffini endings and Pacinian Corpuscles - compression in joints
d) Skin receptors - deformed by changes in joint angle
Receptors for Pain and Temperature?
Detected by free nerve endings - NO ACCESSORY STRUCTURE - open to whatever happens to it. no protection.
Same axon can be receptive to temperature and pain.
Eg. Inflammatory pain
2 Types of Classification for Peripheral Nerve Fibres?
a) Conduction Velocity Used for motor AND sensory but usually motor so alpha motor neurone. A - Fastest: Large diameter, Myelinated B - Smaller but still myelinated C - Smallest, NON-myelinated Motor neurones - conduct APs the fastest
b) Measurements of Diameters Used ONLY for sensory I (Fastest), II, III - Myelinated IV - NOT myelinated, slowest I = A II = B III/IV = C
Basic Anatomy of Spinal Cord?
Gray Bodies - cell bodies - synapses (Inner X portion)
White Bodies - Axons. (Outer portion)
Ascending tracts - body to brain
Descending tracts - brain to body
Dorsal (back) Root
Carries sensory information into the spinal cord
Ventral (front) Root
Motor information
Ventral Horn
Where alpha motor neurone cell bodies are
Dorsal Horn
Sensory neurones
Intermediolateral Horn
Sympathetic neurones (PNS) Contains cell bodies of preganglionic autononomic neurones
Reflexes
Simplest kind of response to a stimulus
Rapid and unprocessed (Doesn’t require command from the brain)
Requires activity in a series of neurones called the Reflex Arc.
Muscle Spindle
Detects STRETCH
Intrafusal muscle fibres inside spindle
Extrafusal muscle fibres AROUND instrafusal
Intrafusal Fibres
a) Nuclear Bag Fibres - usually only one per spindle
b) Nuclear Chain Fibres - Several per spindle
Primary endings
Where group IA fibre enters each spindle and forms spiral endings around both BAG and CHAIN intrafusal fibres.
Rapidly adapting: Signals rate of change of length
Secondary endings
Where several group II fibres enter each spindle
Only innervates nuclear CHAIN fibres
Slowly adapting: Signals absolute length
Y-motor neurones
Can cause contraction of sensory intrafusal fibre - can tune how sensitive muscle spindle fibre is.
Eg. Heights + vertigo = vigorous response. Anxious = higher sensitivity.
Reflex to save you
Monosynaptic Stretch Reflex
Stretch mechanically gated channel > GP > Threshold > gates open and close Na+/K+ > AP > AP propagate electrotonically > myelin > saltatory > capacitance > button > Ca2+ > vesicles dock, fuse, exocytose > binds to receptor, receptor opens > Vm changes > EPSP summates in dedrites temportally + spacially > soma to AP threshold …
Reciprocal Inhibition
Motor neurons of antagonist flexor musles are inhibited due to the simultaneous recruitment of an inhibitory interneuron.
Flex biceps, relax triceps.
Muscle Tone
Background contraction of a muscle in the absence of movement - “Readiness” of a muscle
Results from continuous excitation of Y-motor neurones.
Connected to consciousness*
“The muscle spindle is a way for your body to gain a sense of proprioception, of how your muscles are positioned in the world. Think of the muscle spindle as a little “mini-me” replica of your muscle.
When you want to move your arm muscle, you send 2 signals, one via the alpha motor neuron, and one via the gamma motor neuron. The a-motor neuron contracts your actual skeletal arm muscle. The y-motor neuron contracts your muscle spindle. When you try to get a sense of proprioception, your body doesn’t take readings from your actual skeletal muscle, it takes it from the muscle spindle.
Since the muscle spindle is the “replica” of the muscle, and contracts the same way your actual muscle does, you can take readings from the “replica” to figure out what the real muscle is doing. That’s what the primary endings and secondary endings do. The endings are sensory (afferent) fibers, and they take readings from the muscle spindle. These readings are passed to your brain and your brain now knows what the actual muscle is doing.
Muscle tone is a continuous firing of y-motor neuron, which activates the muscle spindle. So like, in your mind, you’re making that contraction already. This makes your muscle more “Ready” and like ready to contract the actual thing.”
Vestibular Apparatus (VA)
Where information enters from the CNS via cranial nerve 8.
Controls posture, and movements of the body and eyes relative to the external environment.
Consists of:
Semicircular canals 3 on each side (horizontal, anterior, posterior)
Two chambers: UTRICLE and SACCULE
Cochlea
Responsible for the detection of SOUND.
Associated with VA and shares many of its features.
Temporal bone
Hollow interconnecting chambers and cannals embedded in your bone (Bony labrinynth)
Perilymph
Like plasma. Fluid that fills space between bony and membranous fluid. Membrane + Fluid
Bony - FLUID - membrane
Endolymph
High [K+] in this fluid.
Hair cells project into the endolymph.
Bend hair cell, open K channel, K causes depolarization
Ampulla
Expanded region in semicircular canals surrounded by endolymph.
Where sensory organs are - Hair cells are on here and detect movement - ALL HAIR CELLS are oriented in the same direction on any given ampulla.
On Ampulla there is a ridge (Crista) and on the crista is a gelatinous structure (Cupula) - Hairs are embedded in CUPULA.
Hair Cells
Are sensory transducers - convert movement from fluid into chemical information. Related to movement/rotation of your head and in vestibular aparatus.
APICAL SIDE:
Each has 60-100 cilia projecting from its apical pole
Has a BIG Kinocilium and very small Stereocilia (moves relative to kinocilium and are linked together by filaments) oriented in rows of ascending height. Tallest next to kinocilium.
BASAL:
Vesicles containing GLUTAMATE at the base of the cell.
Base of cell surrounded by receptive terminals of cranial nerve 8. (VIII, C8)
Hair cells attached to each other at APICAL tips by TIGHT JUNCTIONS. Only Apical tips and cilia are exposed to endolymph.
How do you know which way, direction, speed of your movement? Rotationary way?
Inertia of the endolymph - lags behind and movement of fluid seems to be going in the opposite direction + hair cells = bending.
Analogy: Drink + ice cubes
What happens when hair cells are bent?
( 1 ) bend stereocilium AWAY from kinocilium = HYPERpolarization - close channels
Reduce amount of glutamate (neurotransmitter) released at base.
( 2 ) bend stereocilium TOWARDS kinocilium = DEPOLARIZATION - opens channels
Depolarization travels from the apical end of the hair cell to the basal end and Vesicles of glutamate are released
Glutamate activates the axons of cranial nerve 8 which fire APs which travel into our brainstem.
How is calcium relevant to hair cells?
Voltage sensitive Ca2+ channels at the base are needed for:
a) Release of glutamate vesicles (neurotransmitter)
b) Stimulation of APs in post-synaptic axon.
Semicircular canals
Arranged in 3 functional pairs: Horizontal, Anterior and Posterior.
On Ampulla there is a ridge (Crista) and on the crista is a gelatinous structure (Cupula) - Hairs are embedded in CUPULA.
Crista
Ridge on Ampulla
Cupula
Gelatinous structure on ridge of ampulla where hairs are embedded in.
Job: to be pushed by endolymph. Perpendicular to fluid flow around ring (semicircular canal?)
How do you detect that your head is rotating?
Rotate RIGHT, Endolymph has inertia and LAGS behind pushing CUPULAE to the LEFT. (Fluid + Ice Cube)
Increases firing of nerves on the right side, decreases firing on left side - tells your brain its moving RIGHT!
What happens when you are continuously rotating at a constant velocity?
Eg. Fluid + Ice Cube - Ice Cubes catch up to the speed of the fluid = same.
Cupula no longer stimulated and returns to starting position.
STOPPING: Fluid (Endolymph) has momentum and continues pushing to the right and you get opposite neuronal firing pattern.
Mismatch between vestibular system and visual system.
Vestibulo-ocular Reflex
Information from semicircular canals causes CVIII firing pattern to change - Affects CIII and CVI to move the eyes appropriately (opposite direction to movement)
Eyes stare at the same thing > move head
What is the function of the Utricle and Saccule?
Gives you the ability to detect your position relative to GRAVITY and ACCELERATION - need multiple orientations of hair cells to detect things.
VS: Semicircular canals - hair cells all in the same orientation.
Together, Utricle and Saccule effectively detect all kinds of horizontal and veritcal movement.
These chambers contain a Macula with hair cells.
Hair cells project into the Otolithic membrane
Macula
Contains hair cells in Urtricle and Saccule.
Equivalent to CRISTA of semicircular canals
Otolithic Membrane
Heavy jello type structure that Hair cells of the Macula stick into.
Contains crystals of Calcium Carbonate (Otoconia) which makes the fluid 5x more DENSE than the surrounding tissue.
Responds to GRAVITY and LINEAR ACCELERATION
Otoconia
Crystals of calcium carbonate embedded in Otolithic Membrane (Jello)
Utricle
(Horizontal Orientation) Macula of UTRICLE forms the FLOOR. Gives information about FRONT-BACK and L/R movements.
Saccule
(Verticle Orientation) Macula of SACCULE forms the WALL. Gives information about FRONT-BACK and UP/DOWN movements.
What is the influence of Utricle and Saccule on Skeletal muscles?
Reflex adjustments of head position and body position (limb muscles)
Have to go to brain stem vestibular nuclei receiving information from VA and separates it out.
Vestibular Apparatus Components
Superior - Eye movements
Medial - Trunk, spinal muscles, neck muscles
Lateral - Limbs lateral to midline
Inferior - Projects to cerebellum (DR KREBS) - coordinates all motor activities.
