Chapter 5 - Synaptic transmission Flashcards Preview

Neuroscience - Structure and Function of the Human Brain > Chapter 5 - Synaptic transmission > Flashcards

Flashcards in Chapter 5 - Synaptic transmission Deck (53):

In which species are electrical synapses common?

In the brains of both invertebrates and vertebrates, including mammals.


What is the process of information transfer at a synapse called?

Synaptic transmission.


What are electrical synapses? Where do electrical synapses occur?

They are synapses that allow the direct transfer of ionic current from one cell to the next. They occur at specialized sites called gap junctions.


What are gap junctions? Where do they occur?

They interconnect many non-neural cells, including epithelial cells, smooth and cardiac muscle cells, liver cells, some glandular cells, and glia.

They occur between cells in nearly every part of the body.


Describe gap junctions' main features. How do they form gap junction channels?

The membranes of two cells are separated by only about 3 nm. The narrow gap is spanned by clusters of special proteins called connexins. There are about 20 different subtypes of connexins, about half of which occur in the brain.

Six connexin subunits combine to form a channel called a connexon, and two connexons (one from each cell) meet and combine to form a gap junction channel.


Describe the gap junction channel.

The gap junction channel allows ions to pass directly from the cytoplasm of one cell to the cytoplasm of the other. The pore of most gap junction channels is relatively large, about 1-2 nm in diameter, big enough for all the major cellular ions and many small organic molecules to pass through.


Describe the directionality of the chemical and electrical synapses.

Since most gap junctions allow ionic current to pass equally well in both directions, electrical synapses are bidirectional.

However, chemical synapses are not bidirectional. In chemical synapses, the message can only travel in one direction.


What is a postsynaptic potential and what does it do?

When two neurons are electrically coupled, an action potential in the presynaptic (i.e., first) neuron causes a small amount of ionic current to flow across the gap junction channel into the other neuron. This is the cause of the Postsynaptic Potential PSP in the second neuron.


Can a PSP incite an action potential?

The PSP is very small, about 1 mV or less at its peak, and may not be strong enough to trigger an action potential itself. However, there are often many electrical synapses from the neuron to other neurons, so several simultaneous PSPs may excite a neuron - an example of synaptic integration.


What roles do electrical synapses play?

They vary from one brain region to another. Often found where normal function requires that the activity of the neighboring neurons is highly synchronized. Deleting functional gap junctions does not alter neurons' abilities to generate oscillations and action potentials but it does abolish the synchrony of these events.


What are the sizes of synaptic clefts, synaptic vesicles, and larger vesicles called secretory granules (also called dense-core vesicles)?

Synaptic cleft: 20-50 nm wide
Synaptic vesicle: about 50 nm in diameter
Secretory granules: about 100 nm in diameter
Note: The synaptic vesicles and secretory granules are often seen in the same axon terminals.


What are membrane differentiations?

Membrane differentiations are dense accumulations of protein adjacent to and within the membranes on either side of the synaptic cleft.


What are "active zones" on the presynaptic side?

Proteins jutting into the cytoplasm of the terminal along the intracellular face of the membrane look like tiny pyramids. They and the membrane associated with them are the actual sites of neurotransmitter release, and therefore called active zones.


What is postsynaptic density?

The protein thickly accumulated in and just under the postsynaptic membrane. They contain the neurotransmitter receptors, which convert the intercellular chemical signal (i.e., neurotransmitter) into an intracellular signal (i.e., a change in membrane potential or a chemical change) in the postsynaptic cell.


What are axodendritic and axosomatic synapses? What about axoaxonic and axospinous?

-If the postsynaptic membrane is on a dendrite, the synapse is axodendritic.
-If the postsynaptic membrane is on the cell body, the synapse is axosomatic.
-If the postsynaptic membrane is on another axon, it's called axoaxonic.
-When a presynaptic axon contacts a postsynaptic dendritic spine, it's axospinous.


What are asymmetrical (or Gray's type I) synapses? What are symmetrical (or Gray's type II) synapses?

Asymmetrical, Gray's type I: Synapses in which the membrane differentiation on the postsynaptic side is thicker than that on the presynaptic side. These are often excitatory synapses.
Symmetrical, Gray's type II: The membrane differentiations are of similar thickness on the post- and presynaptic sides. These are often inhibitory.


What is a neuromuscular junction?

Chemical synapses that occur between the axons of motor neurons of the spinal cord and skeletal muscle. It has many of the structural features of chemical synapses in the CNS.


What is a motor endplate?

The postsynaptic membrane of a neuromuscular junction.


What are the different categories of neurotransmitters?

1) Amino acids
2) Amines
3) Peptides


What are some properties of amino acid and amine neurotransmitters?

They are all small organic molecules containing at least one nitrogen atom, and they are stored in and released from synaptic vesicles.


What are some properties of peptide neurotransmitters?

They are large molecules - chains of amino acids - and are stored in and released from secretory granules.


Where do the different neurotransmitters (amino acids, amines, and peptides) exist?

Since both synaptic vesicles and secretory granules often exist in the same axon terminals, the different neurotransmitters can also often be found from the same axon terminals. The different neurotransmitters are released under different conditions.


Tell a little about the speed of synaptic transmission.

Fast forms of synaptic transmission last around 10-100 msec, and slower forms last from hundreds of milliseconds to minutes. The slower forms occur in the CNS and in the periphery.


Tell about the mediators of synaptic transmission.

Most CNS synapses are mediated by glutamate (Glu), gamma-aminobutyric acid (GABA) or glycine (Gly). The amine acetylcholine (ACh) mediates fast synaptic transmission at all neuromuscular junctions.

The slower synaptic transmissions are mediated by transmitters from all three chemical categories.


Tell about neurotransmitter synthesis.

Different neurotransmitters are synthesized in different ways.
-Glutamate and glycine are among the 20 amino acids that are the building blocks of protein, and they are abundant in all cells of the body, including neurons.
-GABA and the amines are made primarily by the neurons that release them. These neurons contain specific enzymes that synthesize the neurotransmitters from various metabolic precursors. The synthesizing enzymes for both amino acid and amine neurotransmitters are transported to the axon terminal, where they locally and rapidly direct transmitter synthesis.


What happens after the amino acids and amine neurotransmitters are synthesized in the axon terminal?

They must be taken up by the synaptic vesicles. Concentrating the neurotransmitters inside the vesicle is the job of transportes, special proteins embeded in the vesicle membrane.


What mechanisms are used to synthesize and store peptides in secretory granules?

Peptides are formed when amino acids are strung together by the ribosomes of the cell body. In the case of peptide neurotransmitters, it happens in the rough endoplasmic reticulum.

Generally, a long peptide synthesized in the rough ER is split in the Golgi apparatus, and one of the smaller peptide fragments is the active neurotransmitter.

Secretory granules containing the peptide neurotransmitter bud off from the Golgi apparatus and are carried to the axon terminal by axoplasmic transport.


What triggers neurotransmitter release?

The arrival of an action potential in the axon terminal. The depolarization of the terminal membrane causes voltage-gated calcium channels in the active zones to open.

These channels are permeable to Ca2+ and Ca2+ will flood the cytoplasm of the axon terminal as long as the calcium channels are open. The resulting elevation in [Ca2+]_i is the signal that causes the neurotransmitter to be released from synaptic vesicles.


What is exocytosis? Describe the process of exocytosis.

Exocytosis is the release of neurotransmitters from the synaptic vesicles. The membrane of the synaptic vesicle fuses to the presynaptic membrane at the active zone, allowing the contents of the vesicle to spill out into the synaptic cleft.

Exocytosis can occur very rapidly, within 0.2 msec of the Ca2+ influx into the terminal in a squid. Synapses in mammals are even faster. Ca2+ enters the active zone precisely where synaptic vesicles are ready and waiting to release their contents.


What two classes of receptors are neurotransmitter receptors classified into?

Transmitter-gated ion channels and G-protein-coupled receptors.


Tell about transmitter-gated ion channels.

These are membrane-spanning proteins consisting of four or five subunits that come together to form a pore, that is usually closed when no neurotransmitter is present. They generally do not show the same degree of ion selectivity as do voltage-gated channels.


When are transmitter-gated ion channels excitatory and when are they inhibitory?

They are excitatory when they are permeable to Na+ -> this depolarizes the postsynaptic cell, and brings it toward the threshold for generating action potentials.

They are inhibitory when they are permeable to Cl-, since they hyperpolarize the postsynaptic cell -> bring it away from the action potential threshold.


What are EPSPs and IPSPs?

EPSP = Transient postsynaptic membrane depolarization. Caused by the presynaptic release of neurotransmitter. Synaptic activation of ACh-gated and glutamate-gated ion channels causes EPSPs.

IPSP =Transient hyperpolarization of the postsynaptic membrane potential caused by the presynaptic release of neurotransmitter. Synaptic activation of glycine-gated or GABA-gated ion channels cause IPSP.


What are G-Protein-Coupled receptors?

G-Protein Coupled Receptors provide slower, longer lasting, and much more diverse postsynaptic actions than transmitter-gated ion channels.


Describe the process of G-Protein-Coupled receptors.

1. Neurotransmitter molecules bind to receptor proteins embedded in the postsynaptic membrane.
2. The receptor proteins activate small proteins, called G-proteins, which are free to move along the intracellular face of the postsynaptic membrane.
3. The activated G-proteins activate "effector" proteins.


What are second messengers and metabotropic receptors?

Second messengers = Molecules that diffuse away in the cytosol.

Metabotropic receptors = G-protein-coupled receptors, since they can trigger widespread metabolic effects.


What are autoreceptors?

Presynaptic axon terminal receptors that are sensitive to the neurotransmitter released by the presynaptic terminal. Typically, they are G-protein-coupled receptors. They seem to function as a sort of safety valve to reduce release when the concentration of neurotransmitter around the presynaptic terminal gets too high.


Tell about neurotransmitter recovery and degradation.

One way of clearing the neurotransmitter from the synaptic cleft is simple diffusion through the extracellular fluid and away from the synapse.

Most amino acid and amine neurotransmitters have this process aided by their reuptake in the presynaptic axon terminal. They are reloaded into the synaptic vesicles or enzymatically degraded.

Neurotransmitter action can also be terminated by enzymatic destruction in the synaptic cleft, like with ACh removal ad the neuromuscular junction by AChE.

Clearing neurotransmitters is important to avoid desensitization. Inhibition of AChE as in various nerve gases can cause neuromuscular transmission to fail.


What are inhibitors and receptor agonists/antagonists in neuropharmacology?

Inhibitors = Drugs that inhibit the normal function of specific proteins in synaptic transmission.

Receptor antagonists = Inhibitors of neurotransmitter receptors: they block (antagonize) the normal action of the transmitter.

Receptor agonists = Drugs that mimic the actions of the naturally occurring neurotransmitter.


What is synaptic integration?

The process by which multiple synaptic potentials combine within one post-synaptic neuron.


What is quantal analysis of EPSPs?

The elementary unit of neurotransmitter release is the contents of a single synaptic vesicle. Vesicles each contain about the same number of transmitter molecules (thousands). The total released is some multiple of this.

At many synapsis, excytosis of vesicles occurs at some very low rate in the absence of presynaptic simulation. The size of the post-synaptic response can be measured electrophysiologically. This tiny response is a miniature postsynaptic potential, mini, which is generated by the transmitter contents of one vesicle.

Quantal analysis is a method of comparing the amplitudes of miniature and evoked PSPs used to determine how many vesicles release neurotransmitter during normal synaptic transmission.


What is EPSP summation? What is spatial and temporal summation of EPSPs?

Most neurons perform sophisticated computations, requiring many EPSPs to add together to produce a significant post-synaptic depolarization.

EPSP summation represents the simplest form of synaptic integration in the CNS.

Spatial summation = Adding together EPSPs generated simultaneously at many different synapses of a dendrite.

Temporal summation = Adding together of EPSPs generated at the same synapse if they occur in rapid succession, within about 1-15 msec of one another.


Tell a little about dendritic cable properties.

- The synaptic current can take the path inside the dendrite or across the dendritic membrane.
- As the current proceeds down the dendrite, farther from the synapse, the EPSP amplitude will diminish due to the leakage of ionic current through membrane channels.


What are inhibitory synapses?

The action of some synapses is to take the membrane potential away from the action potential threshold. These synapses are inhibitory synapses, and they exert a powerful control over a neuron's output.


What is IPSPs shunting inhibition?

The process through which a synapse prevents current from flowing through the soma to the axon hillock.
At the site of an active inhibitory synapse the membrane potential is approximately equal to E_Cl, -65 mV, which causes positive current to flow outward across the membrane at this site to bring Vm to -65 mV.


What is modulation?

Synaptic activation of G-protein-coupled neurotransmitter receptors that are not directly associated with an ion channel. Synaptic activation of these receptors does not directly evoke EPSPs and IPSPs but modifies the effectiveness of EPSPs generated by other synapses with transmitter-gated channels.


What is meant by quantal release of neurotransmitter?

Post-synaptic EPSPs at a given synapse are quantized; one quant is the contents of one synaptic vesicle. Quantal analysis can be used to find out how many vesicles release neurotransmitter during normal synaptic transmission.


You apply ACh and activate nicotinic receptors on a muscle cell. Which way will current flow through the receptor channels when V_m = -60 mV? When V_m = 0 mV? When V_m = 60 mV? Why?

Nicotonic ACh receptors are permeable to both sodium and potassium. When Vm = –60 mV, net current flow through ACh-gated ion channels is inward, toward the equilibrium potential of sodium, causing depolarization. At Vm = 60 mV, the direction of net current flow through the ACh-gated ion channels is outward, toward the equilibrium potential of potassium, causing the membrane potential to become less positive. The critical value of membrane potential at which the direction of current flow reverses is called the reversal potential. In this case, the reversal potential is 0 mV because this is the value between the equilibrium potentials of sodium and potassium. At 0 mV, no current flows.


This chapter discussed a GABA-gated ion channel that is permeable to Cl-. GABA also activates a G-protein-coupled receptor, called the GABA_B receptor, which causes potassium-selective channels to open. What effect would GABA_B receptor activation have on the membrane potential?

Activated GABA-gated Cl ion channels bring the membrane toward the equilibrium potential for Cl , which is –65 mV. If the membrane potential was less negative than –65 mV when the transmitter was released, activation would cause hyperpolarization. The activation of GABAB receptors causes potassium-selective channels to open. As a result, GABAB activation brings membrane potential toward the equilibrium potential of potassium, which is –80 mV. If the membrane potential was less negative than –80 mV when the transmitter was released, activation would also cause hyperpolarization. This channel might also impact the neuron by shunting inhibition, allowing a depolarizing current from an excitatory synapse to leak out. This, in turn, decreases the likelihood of action potential. The action of a G-protein-coupled receptor is, however, slower than that of the GABA-gated Cl ion channel or a typical excitatory synapse. Therefore, its effects would be slower to occur and would last longer.


A drug called strychnine, isolated from the seeds of a tree native to India and commonly used as rat poison, blocks the effects of glycine. Is strychnine an agonist or an antagonist of the glycine receptor?

Strychnine is an antagonist of glycine at its receptor. Mild strychnine poisoning enhances the startle
and other reflexes and resembles hyperekplexia. High doses can eliminate glycine-mediated inhibition in circuits of the spinal cord and the brain stem. This leads to uncontrollable seizures and unchecked muscular
contractions, spasms, and paralysis of respiratory muscles. It might ultimately result in painful, agonizing death
from asphyxiation.


How does nerve gas cause respiratory paralysis?

Nerve gases interfere with synaptic transmission at the neuromuscular junction by inhibiting AChE.
Uninterrupted exposure to high concentrations of ACh for several seconds leads to a process called
desensitization. In this process, transmitter-gated channels close despite the continued presence of ACh.
Normally, the rapid destruction of ACh by AChE prevents desensitization. However, if AChE is inhibited by
nerve gas, ACh receptors will be desensitized and neuromuscular transmission will fail, causing respiratory


Why is an excitatory synapse on the soma more effective in evoking action potentials in the post-synaptic neuron than an excitatory synapse on the tip of a dendrite?

A current entering the sites of synaptic contact must spread to the spike-initiation zone and this zone
must be depolarized beyond its threshold to generate an action potential. In addition, depolarization decreases
as a function of distance along a dendrite. As a result, the effectiveness of an excitatory synapse for triggering
an action potential depends on how far the synapse is from the spike-initiation zone. Because the soma is closer
to the spike-initiation zone, an excitatory synapse on the soma is more effective for evoking action
potentials than an excitatory synapse on the tip of a dendrite.


What are the steps that lead to increased excitability in a neuron when NE is released presynaptically?

The steps that increase the excitability of a neuron when NE is released presynaptically are:
1. The NE receptor bound to a b receptor activates G-protein in the membrane.
2. G-protein activates the adenylyl cyclase enzyme.
3. Adenylyl cyclase converts ATP into the second messenger cAMP.
4. cAMP activates a protein, kinase.
5. Kinase causes a potassium channel to close by attaching a phosphate group to it.This produces little change
in membrane potential but increases the membrane resistance and increases the length constant of dendrites.
This enhances the response that a weak or a distant excitatory synapse produces. This effect can last longer
than that of the presence of the transmitter.