On the role of glutamate in presynaptic development: Possible contributions of presynaptic NMDA receptors

Karlie N. Fedder, Shasta L. Sabo

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3448-3466
Number of pages19
JournalBiomolecules
Volume5
Issue number4
DOIs
StatePublished - Dec 14 2015

Keywords

  • Glutamate
  • NMDA
  • Presynaptic
  • Synapse formation
  • Synaptogenesis

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