Chapter 5 - Synaptic Transmission

Chemical Synapse

Most synaptic transmission in the mature human nervous system is chemical. The presynaptic and postsynaptic membranes are separated by a synaptic cleft. Synaptic vesicles in the presynaptic membrane store neurotransmitters that are used to communicate across the synaptic cleft. Experiments indicated that many CNS synapses also use a chemical transmitter; in fact, chemical synapses comprise the majority of synapses in the brain.

Transmitter-gated Ion Channels

Neurotransmitter receptors that are membrane-spanning proteins consisting of four or five subunits that form a central pore. When neurotransmitter binds, it conformationally changes to open the pore. Generally do not show the same degree of ion selectivity as voltage-gated ion channels, meaning the cell becomes more permeable to certain other ions while these channels are open.

Voltage-gated Calcium Channels

Neurotransmitter release is triggered by the arrival of an action potential in the axon terminal. The depolarization of the terminal membrane causes Calcium channels to open and flood the cell. This influx of Ca2+ is the signal for the release of neurotransmitter from the synaptic vesicles.

Autoreceptors

Presynaptic receptors that are sensitive to the neurotransmitter released by the presynaptic terminal. Typically are G-protein-coupled receptors that stimulate second messenger formation. Common effect is inhibition of neurotransmitter release and, in some cases, neurotransmitter synthesis. Allows self-regulation of presynaptic terminals.

Transporters

Special proteins embedded in the vesicle membrane which pack/take up the amino acid and amine neurotransmitters into the synaptic vesicles.

Inhibitory Synapses

The action of some synapses is to take the membrane potential away from action potential threshold. They exert a powerful control over a neuron's output.

Temporal Summation

The adding together of EPSPs generated at the same synapse if they occur in rapid succession, within about 1-5 msec of one another.

Spatial Summation

The adding together of EPSPs generated simultaneously at many different synapses on a dendrite.

Neurotransmitter Recovery and Degradation

The importance of transmitter removal from the cleft should not be underestimated. Reuptake into the presynaptic terminal occurs by the action of specific neurotransmitter transporter proteins which also exist in the membranes of glia surrounding the synapse.

Synaptic Integration

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

Endocytosis

The process by which the vesicle membrane is recovered and then refilled with neurotransmitter.

Synaptic Transmission

The process of information transfer at a synapse. Synapses are far more complex than most neuroscientists anticipated.

Exocytosis

The process of releasing the neurotransmitter from the synaptic vesicles. The vesicle membrane fuses to the synaptic membrane at the active zone, allowing the contents to spill out into the synaptic cleft. Very rapid release

Postsynaptic Density

The protein thickly accumulated in and just under the postsynaptic membrane. It contains the neurotransmitter receptors, which convert the intercellular chemical signal into an intracellular signal in the postsynaptic cell.

Membrane Resistance

The resistance to current flowing across the membrane. The value of the length constant will increase as membrane resistance increases because more depolarizing current will flow down the inside of the dendrite. Depends on the number of open ion channels, which changes from moment to moment depending on what other synapses are active.

Internal Resistance

The resistance to current flowing longitudinally down the dendrite. The value of the length constant will decrease as internal resistance increases because more current will then flow across the membrane. Depends only on the diameter of the dendrite and the electrical properties of cytoplasm; relatively constant in a mature neuron.

EPSP Summation

The simplest form of synaptic integration in the CNS. Neurons require EPSPs from multiple other neurons to produce a significant postsynaptic depolarization.

Active Zone

The sites of neurotransmitter release on the presynaptic membrane. Synaptic vesicles are clustered in the cytoplasm adjacent to the active zones.

Neuropharmacology

The study of the effects of drugs on the nervous system tissue.

Types of Neurotransmitters

1)Amino acid/amine: small organic molecules containing at least one nitrogen atom. They are all stored and released from synaptic vesicles. Rapid release through active zones 2) Peptide: Large molecules -- chains of amino acids -- stored in and released from secretory granules. Slow release, not released at every action potential, releases away from action zones.

Metabotropic Receptors

A G-protein-coupled receptor whose primary action is to stimulate an intracellular biochemical response.

Phosphorylation

A biochemical reaction in which a phosphate group (PO42-) is transferred from adenosine triphosphate (ATP) to another molecule. Phosphorylation of proteins by protein kinases changes their biological activity.

Norepinephrine (NE)

A catecholamine neurotransmitter synthesized from dopamine; also called noradrenaline.

Postsynaptic Potential (PSP)

A change in the postsynaptic membrane potential by the presynaptic action of an electrical synapse or a synaptically released neurotransmitter. The PSP generated by a single electrical synapse in the mammalian brain is usually small and may not, by itself, be large enough to trigger an action potential in the postsynaptic cell.

Nicotinic ACh Receptors

A class of acetylcholine-gated ion channel found in various locations, notably at the neuromuscular junction. Found in the muscle and in the CNS (in CNS --> involved in the addictive effects of tobacco use)

Protein Kinases

A class of enzyme that phosphorylates proteins, a reaction that changes the conformation of the protein and its biological activity.

Shunting Inhibition

A form of synaptic inhibition in which the main effect is to reduce membrane resistance, thereby shunting depolarizing current generated at excitatory synapses. Physical Basis: the inward movement of negatively charged chloride ions is formally equivalent to outward flow of positive current. IPSPs reduce the size of EPSPs, making the postsynaptic neuron less likely to fire action potentials.

G-protein-coupled Receptors

A membrane protein that activates G-proteins when it binds neurotransmitter. Can cause slower, longer lasting, and much more diverse postsynaptic actions. 3 steps: 1. Neurotransmitter molecules bind to receptor proteins embedded in the postsynaptic membrane. 2. The receptor proteins activate small proteins, called G-protiens, which are free to move along the intracellular face of the postsynaptic membrane. 3. the activated G-proteins activate the "effector" proteins.

G-proteins

A membrane-enclosed protein that binds guanosine triphosphate (GPT) when activated by a membrane receptor. Active G-proteins can stimulate or inhibit other membrane-enclosed proteins.

Quantal Analysis

A method of comparing the amplitudes of miniature and evoked PSPs, can be used to determine how many vesicles release neurotransmitter during normal synaptic transmission. A single action potential triggers the exocytosis of about 200 synaptic vesicles.

Acetylcholine (ACh)

An amine that serves as a neurotransmitter at many synapses in the peripheral and central nervous systems, including the neuromuscular junction.

Gamma-aminobutyric Acid (GABA)

An amino acid synthesized from glutamate; the major inhibitory neurotransmitter in the central nervous system

Glutamate (Glu)

An amino acid; The major excitatory neurotransmitter in the central nervous system

Glycine (Gly)

An amino acid; an inhibitory neurotransmitter at some locations in the central nervous system.

Adenylyl Cyclase

An enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), a second messenger.

Receptor Agonists

Drugs that bind to receptors and mimic the actions of the naturally occurring neurotransmitter. eg: nicotine, derived from the tobacco plant.

Inhibitors

Drugs which inhibit the normal function of specific proteins involved in synaptic transmission.

Miniature Postsynaptic Potential

Exocytosis of vesicles occurs at some very low rate in the absence of presynaptic stimulation. The size of the postsynaptic response to the spontaneously released neurotransmitter can be measured electrophysiologically. Often called simply, a mini. Each mini is generated by the transmitter contents of one vesicle.

Receptor Antagonists

Inhibitors of neurotransmitter receptors which bind to the receptors and clock (antagonize) the normal action of the transmitter. eg: curare, an arrow-tip poison traditionally used by South American Natives to paralyze their prey.

Gap Junction

Where electrical synapses occur. They are found between cells in nearly every part of the body and interconnect with many non-neural cells, including epithelial cells, smooth and cardiac muscle cells, liver cells, some glandular cells, and glia. The pore of most gap junction channels is relatively large, big enough for all the major cellular ions and many small organic molecules to pass through. Most gap juncitons allow ionic current to pass equally well in both directions --> bidirectional Gap Junctions between neurons and other cells are particularly common early in development - during prenatal and postnatal brain development, they allow neighboring cells to share both electrical and chemical signals that may help coordinate their growth and maturation.

Motor End-plate

the postsynaptic membrane at the neuromuscular junction. Contains a series of shallow folds

Membrane Differentiation

Dense accumulations of protein adjacent to and within the membranes on either side of the synaptic cleft.

Length Constant

A parameter used to describe how far changes in membrane potential can passively spread down a cable such as an axon or a dendrite, represented by the symbol. The length constant is the distance at which the depolarization falls to 37% of its original value; it depends on the ration of membrane resistance (rm) to internal resistance (ri). The longer the length constant, the more likely it is the EPSP generated will depolarize the membrane at the axon hillock. *most current will take the path of least resistance*

Cyclic Adenosine Monophosphate (cAMP)

A second messenger formed from adenosine triphosphate by the action of the enzyme adenylyl cyclase.

Second Messengers

A short-lived chemical signal in the cytosol that can trigger a biochemical response --> activate additional enzymes in the cytosol that can regulate ion channel function and alter cellular metabolism. Their formation is usually stimulated by a first messenger (neurotransmitter or hormone) acting at a G-protein-coupled cell surface receptor. Examples are cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and inositol-1,4,5-triphosphate (IP3)

Secretory Granule aka Dense-core Vesicles

A spherical membrane-enclosed vesicle about 100 nm in diameter containing peptides intended for secretion by exocytosis. The soluble protein appears dark in the electron microscope so they are also called large, dense-core vesicles. Secretory granules containing the peptide neurotransmitter bud off from the Golgi apparatus and are carried to the axon terminal by axoplasmic transport.

Modulation

A term used to describe the actions of neurotransmitters that do not directly evoke postsynaptic potentials but modify the cellular response to excitatory postsynaptic potentials and inhibitory postsynaptic potentials generated by other synapses.

Inhibitory Postsynaptic Potential (IPSP)

A transient hyperpolarization of the postsynaptic membrane potential caused by the presynaptic release of neurotransmitter. (and thus unintentional increase in permeability to Cl-) Synaptic activation of glycine-gated or GABA-gated ion channels cause an IPSP

Excitatory Postsynaptic Potential (EPSP)

A transient postsynaptic membrane depolarization caused by the presynaptic release of neurotransmitter. (and thus unintentional increase in permeability to Na+) Synaptic activation of ACh-gated and glutamate-gated ion channels cause EPSPs.

Neuromuscular Junction

Chemical synapses occurring between the axons of motor neurons in the spinal cord and the skeletal muscle. Transmission is fast and reliable. An action potential in the motor axon always causes an action potential in the muscle cell it innervates. One of the largest synapses in the body. Of considerable clinical significance.

Electrical Synapse

Relatively simple in structure and function, and they allow the direct transfer of ionic current from one cell to the next. Occur at Gap Junctions. Often found where normal function requires that the activity of neighboring neurons be highly synchronized. Bidirectional --> unlike chemical synapses.

Types of CNS Chemical Synapses

axodendritic: postsynaptic membrane is on a dendrite axosomatic: postsynaptic membrane is on a cell body axoaxonic: postsynaptic membrane is on another axon axospinous: presynaptic axon contacts a postsynaptic dendritic spine. dendrodendritic: when dendrites form synapses with one another Asymmetrical synapses (Gray's type I synapses): the memebrane differentiation on the postsynaptic side is thicker than on the presynaptic side. --> usually excitatory Symmetrical synapses (Gray's type II synapses): the membrane differentiations are of similar thickness.--> usually inhibitory