cellular neurobiology midterm 3

Define a Post-Synaptic Potential (PSP).

A voltage change in the postsynaptic cell that results from synaptic signaling.

What is the location and electrical nature of a PSP?

Occurs at the dendrite or soma. It is a graded potential (amplitude can be larger or smaller). It can be either depolarizing or hyperpolarizing.

What is the location and electrical nature of an Action Potential (AP)?

Occurs in the axon. It is all-or-nothing (each AP has the same amplitude

How do PSPs lead to Action Potentials?

A neuron fires when the sum of all PSPs (both excitatory and inhibitory) at the axon hillock reaches the threshold. Generally, one PSP from one synapse is not enough to cause firing

Anatomically, how do Electrical and Chemical Synapses differ?

Electrical: Pre- and post-synaptic cells are directly connected by gap junctions, sharing cytoplasm. Chemical: Cells do not touch, separated by a synaptic cleft (about 20 nm wide).

What are the key molecular components of an electrical synapse?

Connexins which form the gap junctions. Gap junctions are only selective by size.

What are the key electrophysiological properties of an electrical synapse?

The cells fire simultaneously (in synchrony). There is no synaptic delay.

What is a defining electrophysiological property of a chemical synapse?

Synaptic delay of about 0.5-1 ms due to neurotransmitter release. They allow for a variety of different effects in the postsynaptic cell.

Outline the 4 basic steps of synaptic transmission at a chemical synapse.

1. Depolarization opens voltage-gated calcium channels, and calcium enters the presynaptic terminal. 2. Calcium entry triggers exocytosis of vesicles. 3. Neurotransmitters diffuse across the cleft and bind to postsynaptic receptors. 4. Neurotransmitter signaling is ended by degradation or reuptake.

What protein acts as the calcium sensor to allow a vesicle to fuse with the axon membrane?

Synaptotagmin. When it binds calcium, it interacts with SNARE proteins to allow fusion.

How would lowering the amount of calcium in the extracellular fluid change the amplitude of the Postsynaptic Potential (EPP)?

Decrease its amplitude. Less calcium entry means fewer neurotransmitters are released, resulting in a smaller postsynaptic response.

What is the effect of Botulinum toxin (which cleaves the SNARE protein SNAP-25) on the EPP?

Decrease its amplitude (potentially to zero). SNARE proteins are necessary for the vesicle to fuse and release neurotransmitter.

Compare Clear-core vesicles and Dense-core vesicles on their appearance, content, and biogenesis location.

Clear-core: Small and hollow. Small molecule neurotransmitters. Synthesized and filled at the synapse. Dense-core: Large and dark. Neuropeptides (or biogenic amines). Synthesized and filled at the cell body (Golgi apparatus).

Which vesicle pool is released by a single action potential and requires less calcium?

The readily-releasable pool of clear-core vesicles, which are very close to the presynaptic membrane.

Which vesicles require a high-frequency train of electrical stimulation for release (more calcium)?

Clear-core vesicles from the reserve pool and Dense-core vesicles.

What is the function of Clathrin in vesicle recycling?

Clathrin triskelia attach to the vesicular membrane and coat the budding vesicle, physically forcing the membrane into a ball-like shape.

What is the function of Dynamin in vesicle recycling?

Dynamin forms a ring around the "neck" connecting the new vesicle to the plasma membrane and pinches it off.

What is the basic consequence of disrupting vesicle endocytosis?

It is more difficult and slower to make new vesicles, leading to fewer vesicles available for release

What is the "kiss-and-run" hypothesis?

The idea that vesicles can release their neurotransmitters by briefly opening a pore without fully fusing with the plasma membrane.

What is a quantum of neurotransmitter?

The amount of neurotransmitter contained in one vesicle. Since vesicles are roughly uniform, each quantum is a consistent size.

What is the consequence of the uniform size of vesicles on the postsynaptic response?

All postsynaptic voltage responses (e.g., EPPs) should be integer multiples of the voltage response to one vesicle.

How would a decrease in the amount of neurotransmitter loaded into each vesicle (a change in quantum size) affect the quantal release histogram?

It would shift the mV of the peaks (the peaks would be closer to 0 mV), but the responses would still have distinct peaks

What are the three ways neurotransmitter signaling is ended?

1. Diffusion away from the synapse. 2. Reuptake into the presynaptic terminal (or glia) OR Enzymatic Degradation. 3. Receptor Desensitization.

What is the effect of Sarin nerve gas, which inhibits acetylcholinesterase?

Acetylcholine (ACh) persists too long in the synaptic cleft, continuously activating ACh receptors and initially causing too much muscle contraction (paralysis)

Define receptor desensitization

When a neurotransmitter receptor stops passing current even though the neurotransmitter is still present.

How would a mutation that prevents receptor desensitization affect receptor signaling?

It would cause more receptor signaling, as desensitization normally reduces activity.

Distinguish between Ionotropic and Metabotropic receptors.

Ionotropic: Directly linked to an ion channel (ligand-gated ion channels). Fast effect (starts in 1-2 ms). Metabotropic: Affect neurons by activating G-proteins (G-protein-coupled receptors, GPCRs). Slow effect (can last minutes).

What ions flow through the Nicotinic Acetylcholine Receptor (nAChR), and what is the effect on a resting muscle cell?

Permeable to both Sodium and Potassium. At rest, the current is mainly due to Sodium influx, causing depolarization

What ions flow through Ionotropic Glutamate Receptors (GluRs), and what is the effect at rest?

ermeable to both Sodium and Potassium (some also Calcium). At rest, the current is mainly due to Sodium influx, causing depolarization.

What ion flows through the GABA-A receptor, and what is the effect in a mature neuron?

It is a Chloride channel. In a mature neuron, Chloride concentration is high outside the cell, so Chloride flows inward, causing hyperpolarization.

What is the general receptor type for Biogenic Amines and Neuropeptides?

Nearly all of their receptors are Metabotropic (GPCRs).

Ach synthesis enzyme 

choline acetyltransferase(ChAT)

Ach vesicle transporter

vesicular acetylcholine transporter(vAChT)

Ach cleft clearance mechanism

enzymatic degradation by acetylcholinesterase(AChE)

glutamate synthesis enzyme 

glutaminase 

glutamate vesicle transporter

vesicular glutamate transporter (VGLUT)

glutamate cleft clearance mechanism

reuptake by excitatory amino acid transporter(EAAT)

GABA synthesis enzyme 

GAD65 and GAD67 

GABA vesicular transporter

vesicular GABA transporter(VGAT)

GABA cleft clearance mechanism

reuptake by GABA transporters(GATs)

dopamine synthesis enzyme 

tyrosine hydroxylase, DOPA decarboxylase 

dopamine vesicle transporter

vesicular monoamine transporter(VMAT)

dopamine cleft clearance mechanism

reuptake(DAT) and degradation(MAO, COMT)

Compare Small Molecule and Neuropeptide neurotransmitters (synthesis/packaging).

Small Molecule: Small size. Synthesized by enzymes in the presynaptic terminal. Packaged into small, clear-core vesicles. Neuropeptide: Peptides (chains of amino acids). Synthesized by ribosomes in the cell body, packaged by Golgi apparatus. Packaged into large, dense-core vesicles.

How are neurons that release peptide neurotransmitters identified?

By staining (Immunohistochemistry, IHC) for the peptide itself or the mRNA of the peptide.

How are neurons that release small molecule neurotransmitters identified?

By staining for proteins involved in synthesizing, transporting, or clearing the neurotransmitter (since the NTs themselves are too small to stain).

Define a Retrograde Neurotransmitter and give an example.

A molecule that signals "backwards" from the postsynaptic cell to the presynaptic cell. Example: Endocannabinoids

GABA A receptors

ionotropic

cl-channel

GABA B receptors

metabotropic

indirect is to open K+ channel and block Ca 2+ channel

NKCC1

pumps na, cl, and k inside

KCC2

pumps cl- and k outside