Glutamate synapses

Figure 10.2 Site of action of drugs affecting glutamate synapses...

Farber NB, Newcomer JW, Olney JW The glutamate synapse in neuropsychiatric disorders focus on schizophrenia and Alzheimer s disease. Prog Brain Res 116 421-437, 1998... 

Glutamate synapses are specialized for rapid vesicle fusion/neurotransmitter release. Fusion is initiated by SNARE proteins such as syntaxin-1, synaptobrevin-2, and SNAP-25 (see Chapter 2.4 this volume). Presynaptic gene expression, in general, is widely disturbed in schizophrenia (Mimics et al., 2000 Mimics et al., 2001 Hemby et al., 2002), including reduced expression of SNAP-25 RNA(Hemby et al., 2002) and... 

Schematic model of the glutamate synapse. Gly glycine o-Ser D-serine DAAO D-amino acid oxidase DAOA D-amino acid oxidase activator (aka, G72)...

Glutamatergic abnormalities are also a major feature of schizophrenia. They may actually cause the dopaminergic abnormalities in that disorder and then be exacerbated by them (Laruelle et al., 2005). The glutamate hypothesis simply states that NMDAR hypofunction contributes to the pathophysiology of schizophrenia (Coyle, 2006 Lindsley et al., 2006). A variant of this is the NMDA synaptic deficit hypothesis of MacDonald and Chafee (2006), which posits that each risk factor for schizophrenia impacts the NMDA glutamate synapse such that the cumulative effect drives NMDA synaptic function below a threshold for normal function. Supporting either form of the glutamate hypothesis is evidence that... 

Numerous studies have demonstrated synaptic plasticity at the levels of corticostriatal glutamate synapses, exhibiting either LTD or LTP depending on the experimental conditions (see reviews, Centonze et al., 2001 Reynolds and Wickens, 2002). Dl-type receptors and DARPP-32 are required for induction of both LTD and LTP (Calabresi et al., 2000 Kerr and Wickens, 2001). In the hippocampus and prefrontal cortex,... 

Fig. 2. Relative abundance and close packing of different postsynaptic targets of dopaminergic synapses in the striatum. Note the termination of a dopamine (DA) and a glutamate (GLU) presynaptic terminal on the same postsynaptic spine in a minority of cases. Note also that the majority of glutamate synapses are within one or two synapses of a dopamine terminal. GABAergic (GABA) and unknown (UNK) terminals are also shown.

J. Smythies, Redox mechanisms at the glutamate synapse and their significance a review. Eur. J. Pharmacol. 370(1999) 1-7. 

Ottersen OP, Takumi Y, Matsubara A, Landsend AS, Laake JH, Usami S (1998) Molecular organization of a type of peripheral glutamate synapse the afferent synapses of hair cells in the inner ear. Prog Neurobiol 54 127-148. 

Matsubara A, Laake JH, Davanger S, Usami S, Ottersen OP (1996) Organization of AMPA receptor subunits at a glutamate synapse a quantitative immunogold analysis of hair cell synapses in the rat organ of Corti. J Neurosci 76 4457-4467. 

A model glutamate synapse — the lamprey giant reticulospinal axon... 

Let s consider just a few of those effects in brief detail here. In the brain, lead probably corrupts more than one biochemical system. It interferes with events at nerve cell connections called glutamate synapses, which means at approximately half the synapses (connections) in the cerebral cortex. These synapses are apparently critical for learning during development. The important glutamate receptor that s involved is the so-called NMDA (iV-methyl-D-aspartate) receptor. This receptor is selectively blocked by lead, and the behavioral consequence is a deficit in learning ability. 

Saito M, Kawai N, Miwa A, Pan-Hou H, Yoshioka M (1985) Spider toxin (JSTX) blocks glutamate synapse in hippocampal pyramidal neurons. Brain Res 346 397-399 Schafer A, Benz H, Fiedler W, Guggisberg A, Bienz S, Hesse M (1994) Polyamine toxins from spiders and wasps. In Cordell GA, Brossi A (eds) The alkaloids chemistry and pharmacology,... 

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