Neurobiology Exam 1

Trepanation

• A surgical intervention in which a hole is drilled or scraped into the skull, exposing the dura mater to treat health problems related to intracranial diseases

• It is often used to relieve pressure beneath a surface

• Today often called craniotomy

Epidural vs Subdural Hematomas

Epidural hematoma:

◦ Bleeding/clotted blood between the skull and the dura

Subdural hematoma:

◦ Bleeding/clotted blood underneath the dura

◦ It is deeper

Craniectomy VS Craniotomy

• Craniotomy: A piece of skull is removed and then replaced

• Craniectomy: A piece of skull is removed and not replaced

How do neurons communicate with each other?

Chemical communication

◦ One of the first ways cells used to network

◦ Bacteria use this method

◦ Works well, but is limited by diffusion

◦ Example: if perfume is spilled, it takes time for someone on the other side of the room to smell it

◦ Therefore, there needs to be a faster way

Stretching cells

◦ Cells can be brought closer together through stretching

◦ Cells communicate at a synapse

◦ Problem: the signal still has to travel a long way through the cell

Electricity

◦ Provides a faster form of communication

◦ Like how quickly lights in a house turn on

◦ Neurons use electricity

◦ Electrical pulses travel down neurons

What are the two types of aphasia and how do they differ?

• Wernicke’s aphasia

  • Located in the temporal lobe

  • Fluent speech

  • Speech makes no sense

  • Poor comprehension

  • Often less aware that their speech is impaired

  • Usually less frustrated by the speech problem

  • Also called:

    • Sensory aphasia

    • Fluent aphasia

• Broca’s aphasia

  • Located in the frontal lobe

  • Non-fluent speech — struggles to produce words

  • Telegraphic (agrammatical) speech

  • Speech does make sense

  • Good comprehension

  • Usually aware that their speech is impaired

  • Often becomes frustrated because they know what they want to say but struggle to produce it

  • Also called:

    • Motor aphasia

    • Nonfluent aphasia

    • Production aphasia

Stroke

A rapid loss of brain function(s) due to a loss of blood supply to a brain region(s)

Ischemic Stroke VS Hemorrhagic Stroke VS Transient Ischemic Attack

• Ischemic stroke

  • Caused by a blockage in the cerebral blood supply

  • Leads to loss of blood supply to a brain region

• Hemorrhagic stroke

  • Caused by a blow-out/bleeding in the cerebral blood supply

  • Leads to loss of normal blood supply to a brain region

• Transient Ischemic Attack (TIA)

  • Often called a “mini stroke”

What are the 3 Non-Neuron Cell Types?

• There are about 3–10× more non-neurons than neurons in the human brain

• Mast cells

  • Immuno-active cells in the CNS

  • Respond to neuroinflammation

• Microglia

  • Specialized macrophages

• Macroglia

  • Astrocytes/astroglia

    • Regulate the chemical environment

    • Help regulate blood supply

    • CNS

  • Oligodendrocytes/oligodendroglia

    • Form myelin

    • CNS

  • Radial glia

    • Neuron progenitors/stem cells

    • Act as scaffolds and “highways”

    • CNS

  • Schwann cells

    • Form myelin

    • PNS

  • Satellite glial cells

    • Environmental regulation

    • PNS

What cells make myelin in the CNS vs. PNS?

• CNS: Oligodendrocytes / oligodendroglia

• PNS: Schwann cells

What are some approaches to treating epilepsy?

• Surgery

  • Remove the seizure focal point

  • Cut the corpus callosum

    • Helps prevent the seizure from spreading between the two sides of the brain

• Drugs

  • Cause a use-dependent increase in the inactivation time of voltage-dependent Na⁺ channels

  • Enhance GABAergic inhibition

What is the difference between ion channels and ion transporters?

• Ion channels

  • Integral membrane proteins

  • Selective for specific ion(s)

  • Allow passive ion movement across the membrane

  • Ions move in the direction of their electrochemical gradient

• Ion transporters

  • Integral membrane proteins

  • Selective for specific ion(s)

  • Actively move ions across the membrane

  • Move ions opposite to their chemical gradient

  • Maintain chemical gradients across the membrane

What are some important functions of astrocytes?

• Potassium regulation

  • Astrocytes link with each other to widely regulate K⁺

• Blood flow

  • Astrocytes modulate and control blood flow in the brain

• Astrocyte-neuron communication

  • Communicate through Ca²⁺ and gliotransmitter signaling

  • Occurs at the tripartite synapse

How do use-dependent Na⁺ channel-inactivating drugs help treat epilepsy, and what is the drawback?

• The drug increases how long voltage-gated Na⁺ channels stay inactivated

• Inactivated Na⁺ channels cannot reopen right away

• This makes the neuron less excitable and harder to generate another action potential

• Why this helps epilepsy:

  • Seizures involve neurons firing excessively

  • Because the effect is use-dependent, more active Na⁺ channels are affected more

  • This makes highly active/seizure-firing neurons less likely to keep firing

• Possible drawback:

  • Neurons can become too difficult to excite

  • Normal action potential generation may also be reduced

What is the difference between the activation gate and inactivation gate of a voltage-gated Na⁺ channel?

• Activation gate

  • Controls whether the channel pore opens

  • Opens when the membrane is sufficiently depolarized

  • When it opens, Na⁺ can flow through the channel

• Inactivation gate

  • Is separate from the activation gate

  • Quickly blocks the channel after it opens

  • Stops Na⁺ flow even though the activation gate had opened

  • Makes the channel temporarily unable to open again

The 3 states

• Closed

  • Activation gate is closed

  • Inactivation gate is not blocking the pore

  • No Na⁺ flows

  • The channel is ready to open if enough depolarization occurs

• Open

  • Activation gate opens because of depolarization

  • Inactivation gate has not blocked the pore yet

  • Na⁺ flows into the neuron

• Inactivated

  • The inactivation gate blocks the pore

  • Na⁺ can no longer flow

  • The channel is temporarily unable to reopen

What is the difference between the absolute and relative refractory periods?

• Absolute refractory period

  • Cannot generate another action potential

  • Voltage-gated Na⁺ channels are inactivated

  • Because the Na⁺ channels cannot reopen yet, another AP is impossible

• Relative refractory period

  • Another action potential is possible, but harder to generate

  • Some voltage-gated K⁺ channels are still open

  • K⁺ continues leaving the neuron, keeping the membrane closer to Eₖ and farther from threshold

  • Some voltage-gated Na⁺ channels may still be inactivated

  • A stronger stimulus is therefore needed to reach threshold

How does an action potential propagate down an axon?

• Depolarization causes an AP at one site on the membrane

• The nearby membrane then generates another AP

• This repeats down the length of the axon

• Therefore, the AP is a regenerative, high-fidelity process that replicates itself over and over

• AP causes depolarization of the nearby membrane through passive current flow, which decays with distance

If passive current flows in both directions, why does an action potential normally move in only one direction?

• Passive current does move in both directions

• But the membrane behind the AP has inactivated voltage-gated Na⁺ channels

• Those Na⁺ channels cannot reopen yet

• Therefore, another AP cannot be generated backward

• The AP continues forward

What happens if current is injected into the middle of an axon before an action potential has occurred?

• The injected current can open voltage-gated Na⁺ channels and generate an AP

• The AP will travel in both directions

• This happens because voltage-gated Na⁺ channels on both sides are available/active and not yet inactivated

What are the two ways to increase action potential (AP) conduction speed?

• Increase axon diameter

  • The bigger the axon, the faster the action potential travels

  • Example: the squid giant axon is about 1 mm in diameter

  • This is about 100–1000× the size of a mammalian axon

• Add myelin

  • Myelin makes action potentials travel faster by allowing the signal to “jump” over parts of the axon

  • This is called saltatory conduction

What is the Node of Ranvier?

• An unmyelinated, specialized region of the axonal membrane

• Contains the highest density of voltage-gated ion channels on the axon

• Nodes are usually about 1–2 mm apart

  • This is about as far as passive current can reliably travel and still bring the next region to threshold when myelin is present

How does myelin increase action potential propagation?

• Allows passive current to move more effectively down the axon

• Causes less current loss across the membrane

• Capacitance is increased

• There is very little cytoplasm between the plasma membranes that form the myelin sheath

• This effectively creates a thicker membrane, especially in terms of its electrical properties

If myelin is lost (demyelination)

• Passive current may not effectively reach the next Node of Ranvier

• Action potentials can slow down or stop

What is multiple sclerosis (MS) and how does it affect action potentials?

• Multiple sclerosis is a neurodegenerative disease of the CNS

• Involves oligodendrocytes/myelin

• It is an autoimmune disease

• Causes are still poorly understood

• Loss of myelin can cause action potential propagation to slow down or stop

• Signs and symptoms vary greatly:

  • Between different people

  • Over the course of the disease

  • This relates to localization of function and the degenerative nature of the disease

• Some people lose the ability to walk independently

• Others experience long periods of remission

• There is currently no cure

• Treatments can:

  • Speed recovery from attacks

  • Modulate the disease course

  • Manage symptoms

What molecules are involved in synaptic vesicle docking, fusion, and neurotransmitter (NT) release?

• SNARE proteins

  • Help dock synaptic vesicles in place

  • v-SNAREs

    • Located in the vesicular membrane

    • Example: synaptobrevin

  • t-SNAREs

    • Located in the terminal membrane

    • Examples: syntaxin and SNAP-25

• Synaptotagmin

  • Mammals have 15 synaptotagmins

  • Some detect Ca²⁺

  • Involved in docking the synaptic vesicle to the membrane

  • Help trigger fusion of the vesicle with the membrane

  • This fusion allows NT release

How is neurotransmitter (NT) action stopped?

• Diffusion

  • Always a component

• Enzymatic degradation

  • Common for NTs that are proteins, such as neuropeptides

  • Also occurs with ACh

• Reuptake

  • Common for small-molecule NTs

  • NTs are actively taken back from the synaptic cleft

  • Can be taken up by:

    • Presynaptic terminal

    • Perisynaptic glial cells

  • Examples: GABA and glutamate

What different states/pools can synaptic vesicles be in at a chemical synapse?

• Readily releasable pool

  • Vesicles are docked at the active zone

  • Ready to fuse with the presynaptic membrane and release neurotransmitter

• Recycling vesicles

  • Vesicles are being recycled after neurotransmitter release

  • Their membrane is reused to form vesicles again

• Reserve pool

  • Vesicles are stored farther from the active zone

  • Not immediately ready for release

  • Can be recruited when more vesicles are needed

What are the characteristics of a chemical synapse?

• “SLOW BUT SMART”

• Has a physical gap between the presynaptic and postsynaptic cells

  • Called the synaptic cleft

• Information is carried by a chemical signal

  • Called the neurotransmitter (NT)

• Slower than electrical synapses

• Presynaptic terminal:

  • Contains synaptic vesicles

  • Has an active zone

  • Loaded with mitochondria

• Postsynaptic site:

  • Has a postsynaptic density

  • Contains receptors

• Perisynaptic glia are nearby

  • Astroglia in the CNS

  • Schwann cells in the PNS

• A single synapse can release multiple chemical signals

What are the characteristics of an electrical synapse?

• “FAST BUT DUMB”

• Plasma membranes of two cells come together at gap junctions

• Channels form a continuous pore through both cell membranes

• Allows direct current flow from one cell to another

• Very fast

• Ion exchange can be bidirectional

• Useful for synchronizing many neurons

  • Examples: escape in goldfish, ink release in Aplysia

• Current flows through gap junctions

  • Formed by connexins

  • Quaternary structure = connexon

  • Can also allow moderate-sized compounds through

• Also present in glia and muscle

• More common during development in the vertebrate nervous system

• Drawbacks:

  • Bidirectional

  • Less versatile

  • Signal is not amplified

  • Polarity cannot change

  • Less potential for modulation

T or F? neurons can receive input from many synapses simultaneously

True

What are the major types of chemical signaling?

• Classical endocrine signaling

  • Hormones travel in the bloodstream to reach their target

• Paracrine signaling

  • Chemical signal acts on nearby targets

• Autocrine signaling

  • Chemical signal acts on the same cell that secreted it

• Synaptic transmission

  • Neurotransmitters act at synapses

  • Very close-range signaling

• These categories are based mainly on the distance the chemical signal travels from the releasing cell to the target cell(s)

What are the two general categories of neurotransmitters (NTs)?

• Neuropeptides

  • More than 100 known

  • Usually 3–36 amino acids long

  • Examples:

    • Enkephalins

    • Substance-P

    • Somatostatin

    • CART

  • Some act as hormones in one context and neurotransmitters in another

  • Typically synthesized and packaged in dense-core vesicles

• Small-molecule neurotransmitters

  • Monoamines:

    • Serotonin (5-HT)

    • Histamine

    • Octopamine

    • Catecholamines

  • Catecholamines:

    • Dopamine

    • Epinephrine

    • Norepinephrine

  • Acetylcholine

  • Amino acids:

    • Glutamate

    • GABA

    • Glycine

    • Aspartate

  • Purines:

    • ATP

    • Adenosine

  • Packaged in synaptic vesicles

How do neuropeptides and small-molecule neurotransmitters differ in synthesis and packaging?

• Neuropeptides

  • Synthesized like other proteins in the cell

  • Then transported to the axon terminal

• Small-molecule NTs

  • Synthesized, if necessary, in the terminal

  • Packaged in the terminal

  • Some can even be synthesized in the vesicle

What is the difference between anterograde and retrograde axonal transport?

• Anterograde transport

  • Moves material toward the axon terminal

  • Uses kinesin

• Retrograde transport

  • Moves material back toward the cell body

  • Uses dynein

What is the acetylcholine (ACh) life cycle?

• Packaging ACh into vesicles

  • A proton pump creates a proton gradient across the vesicle membrane

  • The ACh transporter uses energy from this proton gradient to move ACh into the vesicle

• Stopping ACh action

  • ACh is degraded in the synaptic cleft by AChE

  • AChE = acetylcholinesterase

• Recycling

  • Choline is transported back into the terminal

  • Choline is used to make more ACh

• The slide identifies a rate-limiting step, but the pasted text does not specify which step it is

• Too much choline can cause:

  • Hypotension

  • Liver damage

What happens to catecholamines after they are released?

• Catecholamines include:

  • Dopamine

  • Norepinephrine

  • Epinephrine

• After release, catecholamines are taken up by neurons and glia

• Uptake occurs through Na⁺-dependent transporters

• These transporters are blocked by cocaine

• Once catecholamines return to the presynaptic terminal, they are either:

  • Repackaged, or

  • Degraded by monoamine oxidase (MAO)

How is serotonin (5-HT) synthesized and recycled?

• Tryptophan → 5-hydroxytryptophan (5-HTP)

  • Enzyme: tryptophan hydroxylase

  • This is the rate-limiting step

• 5-HTP → serotonin (5-HT)

  • Enzyme: 5-HTP decarboxylase

• After serotonin is released:

  • Taken back up by the serotonin transporter

  • Once back in the presynaptic terminal, it is either:

    • Repackaged, or

    • Degraded by MAO (monoamine oxidase)

How are GABA and glutamate taken up and packaged?

• Selectively taken up by:

  • GABA transporters

  • Glutamate transporters

• GABA and glutamate usually do not require synthesis inside the neuron

  • They are pumped in from outside the neuron

  • Na⁺ provides the energy source for uptake

• Packaging into vesicles:

  • GABA vesicular transporters package GABA

  • Glutamate vesicular transporters package glutamate

  • Both use the proton gradient as their energy source

If neuron A inhibits neuron B, and neuron B excites neuron C, what happens to neuron C when neuron A becomes more active?

• A becomes more active

• B gets suppressed

• B fires less

• So B sends less excitatory input to C

• C gets less of a “push” toward threshold

• Therefore C is less likely to fire

If neuron A inhibits neuron B, and neuron B inhibits neuron C, what happens to neuron C when neuron A becomes more active?

• Neuron A inhibits neuron B

• Neuron B therefore becomes less active

• Neuron B normally inhibits neuron C

• If B is less active, it gives less inhibition to C

• So neuron C is released from some inhibition

• This is called disinhibition

• Therefore, neuron C is more likely to fire action potentials

What are postsynaptic potentials (PSPs), EPSPs, and IPSPs?

• Postsynaptic potential (PSP)

  • A change in membrane potential (voltage) in the postsynaptic neuron

  • Because it measures voltage, this is associated with current clamp

• EPSP = excitatory postsynaptic potential

  • Makes the postsynaptic neuron more likely to reach threshold

• IPSP = inhibitory postsynaptic potential

  • Makes the postsynaptic neuron less likely to reach threshold

What are postsynaptic currents (PSCs)?

• A change in membrane current in the postsynaptic neuron

• Recorded in voltage clamp

• Can be:

  • EPSC = excitatory postsynaptic current

  • IPSC = inhibitory postsynaptic current

How do you interpret postsynaptic current/voltage traces?

• PSCs and PSPs appear as curves

• A downward current deflection means:

  • Positive ions are moving into the neuron, or

  • Negative ions are moving out

• To test which ion carries the current:

  • Remove that ion from the extracellular fluid

• ACh channels open because:

  • ACh binds to them

• ACh channels close because:

  • ACh is broken down by acetylcholinesterase

• If the deflection is flipped when comparing figures:

  • One trace may be showing voltage instead of current

What is the reversal potential (Eₛᵧₙ)?

• The membrane potential of a postsynaptic neuron or other target cell at which a neurotransmitter causes no net current flow

• Every synapse has a reversal potential

• The reversal potential depends on which ions are allowed to flow

• Reversal potential and threshold potential determine whether a synapse is excitatory or inhibitory

How does the reversal potential determine whether a synapse is excitatory or inhibitory?

• If Eₛᵧₙ is more positive than threshold:

  • Excitation results

  • The synapse makes the neuron more likely to reach threshold

• If Eₛᵧₙ is more negative than threshold:

  • Inhibition results

  • The synapse makes the neuron less likely to reach threshold

How do you define excitatory and inhibitory synapses using reversal potential?

• Excitatory synapse

  • Activation of a ligand-gated ion channel produces a reversal potential that is depolarized compared with threshold

• Inhibitory synapse

  • Activation of a ligand-gated ion channel produces a reversal potential that is hyperpolarized compared with threshold

How does the reversal potential depend on which ions a synapse allows to flow?

• If only Cl⁻ channels open:

  • Eₛᵧₙ = ECl

• If more than one ion can flow:

  • Eₛᵧₙ lies between the equilibrium potentials of those ions

• Example:

  • If Cl⁻ and K⁺ channels both open, Eₛᵧₙ would be somewhere between ECl and EK

Are synapses that open Cl⁻ channels excitatory or inhibitory?

• Inhibitory

• Example values:

  • Threshold = −50 mV

  • ECl = −65 mV

  • RMP = −70 mV

• Because ECl is more negative than threshold, opening Cl⁻ channels cannot bring the neuron to threshold

• Even a very large number of active Cl⁻ synapses would not bring the cell to threshold

What is synaptic integration?

• A neuron typically receives input from hundreds or thousands of synapses

• Some inputs make the neuron more likely to reach threshold

• Other inputs make it less likely to reach threshold

• The neuron combines:

  • All active synaptic inputs

  • Its intrinsic properties

• The “decision” to fire one or more APs is usually made at the axon hillock

What is the role of the axon hillock/spike initiation zone?

• It is usually where the “decision” to fire an action potential is made

• The membrane voltage must reach threshold at the axon hillock to initiate an AP

• Before the axon hillock reaches threshold, current flow is mostly passive

What happens during passive current flow along a dendrite?

• Local depolarization of one region depolarizes adjacent membrane

• Unlike an action potential, the amplitude decreases with distance

• The amount of decay depends on:

  • Internal resistance

  • Membrane resistance

What is the dendritic length constant (λ)?

The distance from the original depolarization at which the depolarization has decreased to 37% of its original amplitude

What is the difference between spatial and temporal summation?

• Spatial summation

  • Inputs are combined across nearby locations/spaces

• Temporal summation

  • Inputs are combined because they occur close together in time

• Spatial and temporal summation can occur simultaneously

• Summation is not simply addition/subtraction

  • As membrane potential changes, the driving forces also change

Why can the same number of open Na⁺ channels cause a larger depolarization when the resting membrane potential is more negative?

• A more negative RMP creates a larger electrical driving force for Na⁺

• The stronger driving force causes a larger depolarizing effect when the Na⁺ channels open

What are the general properties and locations of neurotransmitter (NT) receptors?

• Most receptors are highly specific for a particular neurotransmitter

• Each neurotransmitter can have many different receptors

• The receptor determines the effect of the neurotransmitter

• NT receptors can be located on:

  • Postsynaptic membrane — always

  • Presynaptic membrane — sometimes

    • Called autoreceptors

  • Perisynaptic glial membrane — usually, maybe always

• Two major categories:

  • Ionotropic receptors

  • Metabotropic receptors

What are ionotropic receptors?

• Ligand/neurotransmitter-gated ion channels

• Ions flow directly through the receptor

• Open very quickly:

  • Within about 0.5 ms to a few ms

• Stay open for tens of milliseconds

• Usually made of 4–5 protein/polypeptide subunits

  • Each subunit has 4 transmembrane domains

• Different combinations of subunits → different receptor subtypes

• Pharmacology can be used to define receptor subtypes

  • Receptor agonists

  • Receptor antagonists

What is an example of an ionotropic receptor?

Nicotinic acetylcholine receptor (nAChR)

• Made of 5 subunits

• Forms an ion channel in the membrane

• Therefore, it is an ionotropic receptor

What is the difference between a receptor agonist and receptor antagonist?

• Receptor agonist

  • Binds to a receptor

  • Mimics the effect of the natural ligand/neurotransmitter

  • Examples:

    • NMDA

    • AMPA

    • Muscarine

    • Nicotine

  • Agonists often give receptor classes their names

    • NMDA and AMPA receptors are glutamate receptors

    • Muscarinic and nicotinic receptors are ACh receptors

• Receptor antagonist

  • Binds to a receptor

  • Blocks the normal action of the neurotransmitter

  • Examples:

    • AP5 → NMDA receptor antagonist

    • CNQX → AMPA receptor antagonist

    • Atropine → muscarinic AChR antagonist

    • Curare → nicotinic AChR antagonist

Why can the same neurotransmitter have different effects?

• The effect depends on which receptor the neurotransmitter activates

• Example:

  • Glutamate is typically excitatory

  • But its exact action depends on the receptor present on the postsynaptic membrane

• Different drugs acting on different glutamate receptors helped reveal different receptor classes

What are the characteristics of the AMPA receptor?

• Ionotropic glutamate receptor

• Gated only by glutamate

• Allows cations to flow in and out of the neuron

• Principal gated ions:

  • Na⁺

  • K⁺

• Typically excitatory

What are the characteristics of the NMDA receptor?

• Ion channel gated by:

  • Voltage

  • Glutamate

  • Low levels of glycine

• For the channel to open:

  • Glutamate must bind

  • Glycine must bind

  • Postsynaptic membrane must be strongly depolarized

• Strong depolarization removes the Mg²⁺ block from the channel

• Useful for producing long-term changes inside the postsynaptic neuron

What happens at a glutamatergic synapse containing both AMPA and NMDA receptors?

• Glutamate is released from the presynaptic terminal

• Glutamate binds to both AMPA and NMDA receptors

• AMPA receptors open

  • Na⁺ flows into the postsynaptic cell

  • Membrane depolarizes

• If depolarization becomes strong enough:

  • The Mg²⁺ plug is forced out of the NMDA channel

• Na⁺ and Ca²⁺ can then flow through NMDA receptors

  • Further depolarizes the membrane

  • Triggers signal-transduction pathways

  • Can recruit other ion channels

  • Can change gene expression in the postsynaptic neuron

What are the characteristics of the GABAₐ receptor?

• A type of GABA receptor

• Usually inhibitory

• Associated with Cl⁻ flow

• A variety of drugs can alter the effect of GABA when it binds to the receptor

• Neurosteroids can also alter GABA effects naturally

What is a neurosteroid?

• A hormone produced inside the brain

• Can be produced by:

  • Neurons

  • Glia

• Can act through paracrine signaling

• Glia can therefore serve as a source of neurosteroids

What are metabotropic receptors?

• G-protein-coupled receptors

• Are NOT ion channels

  • Ions do not flow directly through them

• Typically monomeric

  • One protein

  • 7 transmembrane domains

• Use one or more metabolic steps to cause:

  • Changes in membrane permeability

  • Changes in cellular metabolism through second messengers

• Slower than ionotropic receptors:

  • About 30 ms–1 s

• Effects last longer:

  • Hundreds of milliseconds to minutes or longer

• Use intracellular messengers such as:

  • cAMP

  • IP₃

  • cGMP

• Pharmacology also defines metabotropic receptor subtypes

What is the difference between nicotinic and muscarinic acetylcholine receptors?

• Nicotinic ACh receptor (nAChR)

  • Ionotropic

  • Forms an ion channel

  • Typically allows Na⁺ and K⁺ to flow

  • Found at the neuromuscular junction

  • Curare is an nAChR antagonist

    • Curare is paralytic

• Muscarinic ACh receptor (mAChR)

  • Does NOT form an ion channel

  • Therefore, it is metabotropic

  • Atropine is an mAChR antagonist

How can metabotropic/G-protein-coupled receptors affect a neuron?

• One pathway:

  • Acts through the G-protein β/γ subunits

  • Can quickly alter membrane permeability

• Another pathway:

  • Uses a second-messenger cascade

  • Produces greater signal amplification

  • Can alter membrane permeability or other cellular properties

  • Much slower

How does the β₁-adrenergic receptor produce neuromodulation?

• Typical ligand = norepinephrine

• Norepinephrine is typically made by neurons in the locus coeruleus

• It is then sent to other parts of the brain

• Short-term effect:

  • Can close K⁺ channels

  • These are usually leak channels

• Long-term effect:

  • Activates signal-transduction pathways

  • Can cause changes in gene expression