NEU 201 Quiz 1

neurons and glia, electrical properties, synaptic transmission, dendritic integration, wiring the brain

parts of the neuron

soma (mission control), dendrites (input), axon (output)

dendrites

• type of neurite

• receive synaptic inputs

• most covered in 1000s of spines

• extend from soma

axons

• type of neurite

• release synaptic outputs

• also called boutons

• longest is ~1m+, diameter is 1-25 µm in humans

what makes neurons unique?

• postmitotic (very few generated in adults)

• highly sensitive to O2 deprivation

• sensitive to electricity

neuron functions

• specialized for electrical signaling over long distances

• receive signals from sensory organs and other neurons

• integrate and transmit information

how do neurons encode information?

in the timing of action potentials and the number and distribution of firing neurons

definition of the action potential

a transient change in membrane voltage relative to the inside and outside of the cell

Nissl stain

labels nuclei of neurons and helps to see layers of brain tissue

Golgi stain

labels 5% of neurons

Golgi’s reticular theory vs. Cajal’s neuron doctrine

reticular theory: a single continuous network controls the nervous system

neuron doctrine (correct): individual neurons that communicate with each other make up the nervous system

problems that arise with bigger brains

problems of speed and distance

solutions to distance problem of bigger brains

• neuronal geometry (meters-long axons)

• active transport of proteins

• local synthesis of proteins at synapses

solutions to speed problem of bigger brains

• larger axon diameter (conduction increases with sqrt of diameter)

• myelin insulation (conduction increases 10x)

active transport

• usually how proteins are moved from ribosomes in soma to the neurites

• axonal motor proteins “walk” proteins along microtubules of the cytoskeleton

destination of retrograde active transport

the soma

destination of anterograde active transport

the axon terminal

motor protein for retrograde active transport

dynein

motor protein for anterograde active transport

kinesin

cytoskeleton

• provides structural integrity and motility

• consists of microtubules (20nm), filamentous actin (microfilaments; 5nm), neurofilaments (10nm)

what are glia?

non-neuronal support cells in the nervous system

glia found in the central nervous system

• microglia

• macroglia

  • astrocytes, oligodendrocytes, ependymal cells, radial glia

glia found in the peripheral nervous system

• macroglia

  • Schwann cells, satellite cells

astrocytes

• 20-40% of glia in the central nervous system

• buffer extracellular ions/neurotransmitters

• structurally and functionally diverse

• express neurotransmitter receptors

oligodendrocytes

• type of macroglia in the central nervous system

• myelinates axons, with one covering many axons at once

microglial cells

• type of glial cells found in the central nervous system

• involved in the immune response, acting as resident macrophages that carry out axon pruning

ependymal cells

• type of glial cells found in the central nervous system

• generate cerebrospinal fluid (CSF)

Schwann cells

• type of macroglia found in the peripheral nervous system

• myelinate axons, with one cell covering one axon

biological basis of multiple sclerosis

autoimmune attack on myelin sheath and oligodendrocytes

role of axons and dendrites in the nervous system “RC circuit”

act as wires that require active propagation of signal

membrane capacitance

the ability of the membrane to store electrical charge

membrane resistance (for neuronal RC circuit)

how much the membrane impedes the flow of current

Ohm’s Law

V = IR (V = voltage, I = current, R = resistance)

conductance (g)

the relative ability of a charge to move (g = 1/R); imparted by ion channels

the major influences on the movement of ions across the neuronal membrane

• concentration (diffusion down concentration gradients)

• charge (like charges repel and opposites attract)

electrochemical gradient

the driver of ion movement, describes the concentrations and charges and both sides of the membrane

two key determinants of ion fluxes

• the selective permeability of the membrane to different ions due to ion channels

• the non-uniform distribution of ions on either side of the membrane due to active transporters

usual relative concentrations of important ions in neuroscience

inside: more K+

outside: more Na+, Cl-, Ca2+

membrane potential (Vm)

the difference in electrical charge (voltage) between the inside of a cell relative to the outside

electrochemical equilibrium

state where there is no net flow of an ion through open channels

Nernst equation

• used to find the equilibrium potential (aka Nernst potential, reversal potential) for an ion

• assumption is that the membrane is selectively permeable for just the ion of interest

Goldman-Hodgkin-Katz equation

• generalizes the Nernst equation for multiple ions of differing permeability

• ratio of concentrations flips for anions (in/out rather than out/in)

~80 mV

usual resting membrane potential; due to membrane being most permeable to K+

difference that causes the driving force on an ion

difference between the ion’s Nernst potential and the membrane potential

depolarization

when the neuron becomes more positive

hyperpolarization

when the neuron becomes more negative

why is the baseline voltage of a neuron negative?

the membrane is a capacitor; Vm is measured at the membrane surface and although it is affected by ion flows, ion flows do not really change total concentrations

• the Na+/K+ pump maintains a negative resting membrane potential

it takes time for the membrane (capacitor) to charge

why do neurons’ voltage respond slowly to injected current?

membrane surface area

capacitance and time constant tau (charging time) increases as ____ increases

ion channels

transmembrane proteins that are selectively permeable to specific ions

why can’t Na+ pass through K+ ion channels, even though Na+ is smaller than K+?

the channel removes a hydration shell from K+ and this shell is harder to remove from Na+

important features of ion channels

• gating

• selectivity

• permeability

• kinetics

• modulation by neurotransmitters

• pharmacology

in the neuronal RC circuit, open ion channels impart…?

conductance is imparted

what can make ion channels open and close?

• neurotransmitter binding to ionotropic receptors

• changes in membrane potential (voltage)

• metabotropic signaling

• etc.

active transporters

proteins that move ions against their electrochemical gradients; maintain concentration differences that are needed for membrane potential to exist

Na+/K+ pump

active transporter protein that is required for the negative resting membrane potential

• pumps out 3 Na+ with every 2 K+ brought in

key characteristics of an action potential across species

• rapid change toward more positive membrane potential (depolarization)

• all-or-none

• regenerative

• unidirectional

• transmitted from neuron to neuron

phases of the action potential

rising, falling, undershoot, return to resting Vm

findings of Hodgkin-Huxley experiments

• biophysical basis of action potentials;

• decreasing [Na+]_ext decreases action potential amplitude

  • action potential amplitude depends on Na+’s Nernst potential

• Na+ channels open transiently soon after depolarization, then inactivate

• K+ channels open more slowly and aren’t so transient

voltage clamp

allows one to hold membrane voltage constant while measuring the injected current needed to maintain that voltage as current is carried by open ion channels

events in an action potential

1. neuron is at resting membrane potential

2. the cell depolarizes and Vm reaches a threshold for voltage-gated Na+ channel activation

3. Na+ channels open, bringing Na+ influx (rising phase)

4. after 1ms, Na+ channels inactivate, blocking Na+ from moving through

5. voltage-gated K+ channels activate and K+ begins to leave the cell (efflux)

6. K+ leaves the cell, bringing Vm down (falling phase)

7. Na+ channels deinactivate (absolute refractory period) and K+ channels close (relative refractory period)

8. extra K+ diffuses out, lowering Vm below the resting potential (undershoot)

9. the neuron returns to resting membrane potential thanks to the Na+/K+ pump

ball-and-chain model of voltage-gated Na+ channel inactivation

1. at Vrest —> closed, not inactivated — no ion flow

2. with depolarization to +40mV —> open, not inactivated — ions flowing

3. after 1ms —> open, inactivated — no ion flow

4. with repolarization —> closed, not inactivated

absolute refractory period

inactivation of voltage-gated Na+ channels prevents an action potential from firing no matter what

relative refractory period

until voltage-gated K+ channels close completely, more depolarization is needed to reach action potential threshold

fast positive feedback loop and slow negative feedback loop

for Na+ and K+, respectively — responsible for Vm changes during an action potential

• depolarization opens Na+ channels, which increases Na+ influx — which depolarizes cells further

• depolarization opens K+ channels, which increases K+ efflux — which hyperpolarizes cells

nodes of Ranvier

• gaps in myelin on axons that exhibit many V-gated Na+ and K+ channels

• allow for saltatory conduction

saltatory conduction

where a signal skips along one gap (node of Ranvier) to the next down an axon — involving both passive and active current flow

regenerative property of action potentials

• propagation without attenuation

• passive spread along axon depolarizes adjacent areas and activates new V-gated Na+ channels

• new replicate APs are generated at each node of Ranvier

synapses

sites of cellular connection (transmission), found between neurons or neurons with other cell types

electrical synapses

• allowing ions to flow directly from one cell to another through gap junctions

• less common than chemical synapses

• fast, bidirectional

• can synchronize cells

gap junctions

• the 3nm separation spaces between neurons at a chemical synpase, with gap junction channels (2 connexons, with 1 connexon = 6 conexins)

• larger than ion channels, relatively nonspecific

chemical synapses

• vesicles containing neurotransmitters are released by one cell’s pre-synaptic terminal into the synaptic cleft to reach receptors on the postsynaptic terminal

• typical synapse in humans

• vary in size, shape, distribution

• able to amplify small signals

• different timescales and outcomes

• change in strength with experience

asymmetrical membrane differentiations

in chemical synapses, more often associated with excitatory signals

symmetrical membrane differentiations

in chemical synapses, more often associated with inhibitory signals

the neuromuscular junction (NMJ)

• junction between motor neuron and muscle cell

• used to discover key principles of synaptic transmission

• features folds in postsynaptic membrane

what happens when you block ACh receptors at the NMJ?

no EPP

what happens when you add ACh to the NMJ?

increase in EPP amplitude and duration

what happens when you inhibit AChE?

EPP amplitude and duration increase

voltage-gated Ca2+ channels

allow Ca2+ to flow into presynaptic terminal during depolarization, triggering neurotransmitter release

an influx of __ into the presynaptic bouton triggers the release of neurotransmitters

Ca2+

SNAREs

complex at presynaptic membrane that facilitates exocytosis (vesicle fusion)

spontaneous mini EPPs (mEPPs)

evidence of neurotransmitters being released in discrete packets

paired-pulse facilitation

in neurons with low probability of vesicle release, when residual Ca2+ in the presynaptic bouton causes the second signal to be greater than the first

paired-pulse depression

in neurons with high probability of vesicle release, when vesicles are depleted and cause the second signal to be weaker than the first

criteria for defining a neurotransmitter

1. released by presynaptic neuron upon electrical stimulation

2. made and stored in the presynaptic neuron

3. sufficient to mimic a response to stimulation

Dale’s principle

most neurons release one main neurotransmitter

classes of neurotransmitters

amino acids, amines, peptides

endocannabinoids

small lipids that go from post-synaptic to pre-synaptic cell, regulating transmitter release from pre-synaptic cell

ionotropic receptors

• aka ligand-gated ion channels

• neurotransmitter binds, channel opens, then ions flow through

• made up of 3-5 subunits with pore in middle

AMPA and NMDA

main ionotropic receptors for glutamate; both around equally permeable to Na+ and K+, so depolarizing at Vrest

the excitatory/inhibitory nature of a neurotransmitter depends on…

the ions its channels pass

excitatory response

depolarization; bringing closer to AP

inhibitory response

hyperpolarization; bringing further from AP

nicotinic AChRs

• acetylcholine receptors

• pass both Na+ and K+ —> Vm = 0 (depolarized)

V_rev

• reversal potential

• V at which current flow switches between inward and outward

• can tell us about what ions a channel passes

glutamate

most common excitatory neurotransmitter

GABA

most common inhibitory neurotransmitter - receptors are permeable to Cl^-

receptor agonists

activate receptor (causing effect)

receptor antagonists

inhibits binding to receptor (blocking effect)

tetanus

• toxin that is antagonist of SNAREs

• blocks GABA, an inhibitory neurotransmitter

• results in rigid paralysis

Botulinum toxins

• antagonist of SNAREs

• blocks ACh, an excitatory neurotransmitter

• results in flaccid paralysis