Glutamatergic neurons

Glutamate (Glu) is the most abundant amino acid in the CNS. About 30% of the total Glu acts as the major excitatory neurotransmitter in the brain. Glu is synthesized in the nerve terminals from tw o sources from glucose via the Krebs cycle and from glutamine by the enzyme glutaminase. The production of the neurotransmitter glu is regulated via the enzyme glutaminase. Glu is stored in vesicles and released by a Ca dependent mechanism. 

Glu acts at three different types of ionotropic receptors and at a family of G-protein coupled (metabotropic) receptors. Binding of glu to the ionotropic receptors opens an ion channel allowing the influx of Na+ and Ca + into the cell. 

The metabotropic receptor family includes at least seven different types of G-protein coupled receptors (mGluRl-7). They are linked to different second messenger systems and lead to the increase of intracellular Ca or the decrease of c/kMP. The increase of intracellular Ca leads to the phosphorylation of target proteins in the cell. 

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Ascending SLD PS-on glutamatergic neurons would induce cortical activation via their projections to intralaminar thalamic relay neurons in conjunction with W/PS-on cholinergic and glutamatergic neurons from the LDT and PPT,... 

Hertz, L. and Schousboe, A. (1987) Primary cultures of GABAergic, and glutamatergic neurons as model systems to study neurotransmitter functions. I. Differentiated cells, in Model Systems of Development and Aging of the Nervous System (Vemadakis, A., Privat, A., Lauder, J. M., Timiras, P. S and Giacobini, E eds.), M. Nijhoff Publishing Company, Boston, MA, pp. 19-31. 

Glutamatergic neurons are widely distributed throughout the entire brain. Most glutamatergic neurons are so-called projection neurons their axon projects into distant brain regions. Prominent glutamatergic pathways are the connections between different regions of the cerebral cortex (cortico-cortical projections), the connections between thalamus and cortex, and the projections from cortex to striatum (extrapyramidal pathway) and from cortex to brain stem/spinal chord (pyramidal pathway). 

The hippocampus is characterized by a series of glutamatergic neurons, which can create rhythms of electrical activity necessary for the generation of memory traces in the brain. The cerebellum, a region dedicated to the temporal processing of motor and cognitive in-... 

The widespread distribution of glutamatergic neurons explains why glutamate is involved in many brain functions. Modulation of glutamatergic activity is therefore most likely to have widespread effects. Excess stimulation of glutamatergic receptors, as seen in seizures or stroke, can lead to unregulated Ca + influx and neuronal damage (Dingledine et ah, 1990 Coyle and PuTtfarcken, 1993 Loscher, 1998). 

Several brain functions have been linked to specific glutamate receptor subtypes in selected brain regions. For example, glutamatergic neurons and NMDA receptors in the hippocampus are important for longterm potentiation (FTP), a crucial component in the formation of memory (Wilson and Tonegawa, 1997). Animal models with selective lesioning or strengthen-... 

FIGURE 2.3 Glutamatergic synapse. Glutamate binds to ionotropic receptors (1) and metabotropic receptors (2). The glutamate transporter (3) pumps glutamate back into the glutamatergic neuron. 

Figure 30-13 Section through a rat brain. This brain, which has been very widely used in neurochemical studies, appears superficially to be quite different from the human brain (Fig. 30-1), which is characterized by its large cerebral cortex. However, basic pathways are the same. Some major pathways for glutamate-secreting (glutamatergic) neurons are marked by arrows. Most of these originate in the neocortex (outer layers of the cerebral cortex) and the hippocampus. From Nicholls.149 Courtesy of David G. Nicholls.

The stargazer mutant mouse is ataxic and epileptic. It lacks functional AMPA receptors (Fig. 30-1), which apparently are not delivered successfully to the synapses in the cerebellum in which they function.380 386 Mutation of a transmembrane protein stargazin, which may interact with the AMP receptor, causes the symptoms.457 458 NMDA receptors (Fig. 30-20) are involved in synapse formation in the brain. Filopodial extensions on dendrites, triggered by electrical activity, are essential for synapse formation,459 which occurs rapidly.4593 Activation of NMDA receptors is apparently also necessary.379 460 Without this stimulation the excitatory glutamatergic neurons of the developing brain undergo apoptosis. 

Table 1. Location of H3 heteroreceptors inhibiting the release of monoamines, acetylcholine and glutamate in the brain. To prove or disprove the presynaptic location of H3 receptors, transmitter release was studied in isolated nerve endings (synaptosomes) or in brain slices superfused with K+-rich Ca2+-free medium containing tetrodotoxin (TTX) (in the latter case, transmitter release was evoked by introduction of Ca2+ ions into the medium). The experimental approaches used in the electrophysiological study to show the presynaptic location of H3 receptors on glutamatergic neurones are described in the text.

Scruggs JL, Patel S, Bubser M, Deutch AY. DOI-Induced activation of the cortex dependence on 5-HT2A heteroceptors on thalamocortical glutamatergic neurons. J Neurosci 2000 20 8846-8852. 

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