Assembly of Excitatory Synapses in the Absence of Glutamatergic Neurotransmission

Neuron. 2017 Apr 19;94(2):312-321.e3. doi: 10.1016/j.neuron.2017.03.047.


Synaptic excitation mediates a broad spectrum of structural changes in neural circuits across the brain. Here, we examine the morphologies, wiring, and architectures of single synapses of projection neurons in the murine hippocampus that developed in virtually complete absence of vesicular glutamate release. While these neurons had smaller dendritic trees and/or formed fewer contacts in specific hippocampal subfields, their stereotyped connectivity was largely preserved. Furthermore, loss of release did not disrupt the morphogenesis of presynaptic terminals and dendritic spines, suggesting that glutamatergic neurotransmission is unnecessary for synapse assembly and maintenance. These results underscore the instructive role of intrinsic mechanisms in synapse formation.

Keywords: active zone; dendritic spine; glutamate release; hardwiring; hippocampus; memory; neural circuit development; neurotransmission; synapse; synaptic vesicle exocytosis.

MeSH terms

  • Animals
  • Dendrites / physiology
  • Dendritic Spines / physiology
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / metabolism
  • Hippocampus / metabolism*
  • Mice
  • Neurogenesis / physiology
  • Presynaptic Terminals / metabolism*
  • Synapses / metabolism*
  • Synapses / physiology
  • Synaptic Transmission / physiology


  • Glutamic Acid