Skip to main content

Block Rockin' Beats - Glutamate Excitation and GABA Inhibition

I'm currently reading Joseph LeDoux's excellent book "Synaptic Self" - I highly recommend it. Chapter 3 of the book - "The Most Unaccountable Machinery" - does a splendid job of covering the basic working mechanisms of neurons, axons, dendrites and synapses, as well as the history behind some of the most important discoveries in neurobiology. The section covering inhibition was particularly enlightening for me, so I'd like to use this post to capture the key points on inhibition and the roles of Glutamate and GABA.
In a previous post (Neurotransmitters - molecular messages), the following definition of GABA was quoted from another excellent (and free!) book: "Discovering the Brain" by Sandra Ackerman: GABA (gamma-aminobutyric acid) often acts as a fast synaptic transmission inhibitor. Unlike dopamine or serotonin, which have diverse roles, GABA consistently acts as an “off” signal; the cerebellum, retina, and spinal cord all use this transmitter to inhibit signals, as do many other parts of the brain and nervous system. GABA's inhibitory effect comes about in the following way: the transmitter opens a channel in the membrane through which negatively charged chloride ions can enter the cell. This influx hyperpolarizes the cell and makes it less likely to be excited by incoming stimuli. GABA receptor sites show some tendency to bind barbiturates and the “minor tranquilizers,” the benzodiazepines. Curiously, the presence of GABA in low concentrations enhances the binding of benzodiazepines to receptor sites. This pattern indicates that GABA and the benzodiazepines cannot be competing for exactly the same sites. Instead, an array of recent studies have yielded the view that the GABA receptor site is in fact a multifunctional set of proteins that contain the chloride ion channel and distinct subsites for binding of benzodiazepines, other tranquilizers such as barbiturates, and GABA itself.
Unlike GABA, Glutamate (the 'G' in MSG) is an excitatory neurotransmitter. Dr. LeDoux refers to Glutamate and GABA as "The Chemical Brothers" (hence this post's title :) )

From Synaptic Self: Inhibition is a very useful device in neural circuits. It adds termendously to the specificity of information processing, filtering out random excitatory inputs, preventing them from triggering activity. Only if the excitatory inputs arrive simultaneously can they overcome the inhibition and elicit activity. And once activity is elicited, inhibition is important for keeping the excitation in check and resetting the circuit.

From Wikipedia: GABA acts by binding to specific receptors in the plasma membrane of both pre- and postsynaptic cells. This binding causes the opening of ion channels to allow either the flow of negatively-charged chloride ions into or positively-charged potassium ions out of the cell. This will typically result in a negative change in the transmembrane potential.

Three general classes of GABA receptor are known. These include GABAA and GABAC ionotropic receptors, which are ion channels themselves, and GABAB metabotropic receptors, which are G protein-coupled receptors that open ion channels via intermediaries


From The Synaptic Self:Glutamate receptors (such as the NMDA receptor) tend to be located out on the dendrites, especially in the spines, whereas GABA receptors tend to be found on the cell body, or on the part of dendrites close to the cell body. In order for glutamate-mediated excitation to reach the cell body to help trigger an action potential, it has to get past the GABA guard. Excitation coming down a dendrite and headed for the cell body can be extinguished by GABA.

Without GABA inhibition, neurons would send out action potentials continuously under the influence of glutamate, and would eventually literally fire themselves to death. ... Overactivity of glutamate, and the resulting injury to neurons, actually plays an important role in stroke and other vascular disorders of the brain, as well as in epilepsy and possibly Alzheimer's disease.

Comments

Popular posts from this blog

Perkinjes and Granules and Schwanns, oh my...

It's tempting to oversimplify things.  Like neurons.  It would be nice if there were one type of neuron, and all you needed to know about how neurons work could be clearly labelled on a diagram of that one type of neuron.  Well, nature LOVES to specialize.  So, before getting deeper into how neurons work, I thought it would be good to take a step back and get some vocabulary in place...The BasicsFrom University of Washington's 'Neuroscience for kids':Neurons come in many different shapes and sizes. Some of the smallest neurons have cell bodies that are only 4 microns wide. Some of the biggest neurons have cell bodies that are 100 microns wide.  Neurons are similar to other cells in the body because: Neurons are surrounded by a cell membrane. Neurons have a nucleus that contains genes. Neurons contain cytoplasm, mitochondria and other "organelles". Neurons carry out basic cellular processes such as protein synthesis and energy production. However, neurons diff…

Neurotransmitters - molecular messages

You often hear about neurotransmitters in the news and in science magazines in a kind of off-hand way that assumes everyone must surely know what these things are. But, um, what are they, exactly?

From Sandra Ackerman's book "Discovering the Brain": To be recognized as a neurotransmitter, a chemical compound must satisfy six conditions: It must be

synthesized in the neuron, stored there, released in sufficient quantity to bring about some physical effect; when administered experimentally, the compound must demonstrate the same effect that it brings about in living tissue; there must be receptor sites specific to this compound on the postsynaptic membrane, as well as a means for shutting off its effect, either by causing its swift decomposition or by reuptake, absorbing it back into the cell.

OK, well, what about hormones? They're chemical messengers too - how are hormones different from neurotransmitters? A hormone, by definition, is a compound produced by an endocrine…

Receptors - getting the message across

From Paul Greengard's Nobel Lecture in 2000:
It is estimated that there are about 100 billion nerve cells in the brain and that on average each of these nerve cells communicates with 1000 other nerve cells. A vigorous debate went on from the 1930s through the 1960s as to whether intercellular communication across the synapses between nerve cells was electrical or chemical in nature. The electrical school of thought held that the nerve impulse or action potential was propagated along the axon to the nerve ending, changed the electrical field across the postsynaptic plasma membrane, and thereby produced a physiological response. The chemical school believed that when the action potential came down the axon to the nerve terminal, it caused the fusion of neuro-transmitter-containing vesicles with the presynaptic plasma membrane, releasing a neurotransmitter, which then diffused across the synaptic cleft and, through activation of a (hypothetical) receptor, produced a physiological resp…