A Glutamate Homeostat Controls the Presynaptic Inhibition of Neurotransmitter Release

Cell Rep. 2018 May 8;23(6):1716-1727. doi: 10.1016/j.celrep.2018.03.130.

Abstract

We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ). We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes. Furthermore, homeostatic depression is only induced through excess presynaptic glutamate release and operates with disregard to the postsynaptic response. We propose that two independent homeostats modulate presynaptic efficacy at the Drosophila NMJ: one is an intercellular signaling system that potentiates synaptic strength following diminished postsynaptic excitability, while the other adaptively modulates presynaptic glutamate release through an autocrine mechanism without feedback from the postsynaptic compartment.

Keywords: Drosophila neuromuscular junction; glutamate homeostasis; homeostatic synaptic plasticity; synaptic depression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / physiology*
  • Glutamic Acid / metabolism*
  • Homeostasis*
  • Long-Term Potentiation
  • Mutation / genetics
  • Neural Inhibition / physiology*
  • Neuromuscular Junction / physiology
  • Neurotransmitter Agents / metabolism*
  • Presynaptic Terminals / physiology*
  • Receptors, Glutamate / metabolism
  • Synaptic Vesicles / metabolism

Substances

  • BRP protein, Drosophila
  • Calcium Channels
  • Drosophila Proteins
  • Neurotransmitter Agents
  • Receptors, Glutamate
  • Glutamic Acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium