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On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors

Departments of Pharmacology and Neuroscience, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Author to whom correspondence should be addressed.
Academic Editor: Kenneth E. Miller
Biomolecules 2015, 5(4), 3448-3466;
Received: 28 May 2015 / Revised: 22 October 2015 / Accepted: 26 November 2015 / Published: 14 December 2015
(This article belongs to the Special Issue Role and Regulation of Glutamate Metabolism)
Proper formation and maturation of synapses during development is a crucial step in building the functional neural circuits that underlie perception and behavior. It is well established that experience modifies circuit development. Therefore, understanding how synapse formation is controlled by synaptic activity is a key question in neuroscience. In this review, we focus on the regulation of excitatory presynaptic terminal development by glutamate, the predominant excitatory neurotransmitter in the brain. We discuss the evidence that NMDA receptor activation mediates these effects of glutamate and present the hypothesis that local activation of presynaptic NMDA receptors (preNMDARs) contributes to glutamate-dependent control of presynaptic development. Abnormal glutamate signaling and aberrant synapse development are both thought to contribute to the pathogenesis of a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, epilepsy, anxiety, depression, and schizophrenia. Therefore, understanding how glutamate signaling and synapse development are linked is important for understanding the etiology of these diseases. View Full-Text
Keywords: glutamate; NMDA; presynaptic; synaptogenesis; synapse formation glutamate; NMDA; presynaptic; synaptogenesis; synapse formation
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Fedder, K.N.; Sabo, S.L. On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors. Biomolecules 2015, 5, 3448-3466.

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