Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord. Academic Article uri icon

Overview

abstract

  • Circuit function in the CNS relies on the balanced interplay of excitatory and inhibitory synaptic signaling. How neuronal activity influences synaptic differentiation to maintain such balance remains unclear. In the mouse spinal cord, a population of GABAergic interneurons, GABApre, forms synapses with the terminals of proprioceptive sensory neurons and controls information transfer at sensory-motor connections through presynaptic inhibition. We show that reducing sensory glutamate release results in decreased expression of GABA-synthesizing enzymes GAD65 and GAD67 in GABApre terminals and decreased presynaptic inhibition. Glutamate directs GAD67 expression via the metabotropic glutamate receptor mGluR1β on GABApre terminals and regulates GAD65 expression via autocrine influence on sensory terminal BDNF. We demonstrate that dual retrograde signals from sensory terminals operate hierarchically to direct the molecular differentiation of GABApre terminals and the efficacy of presynaptic inhibition. These retrograde signals comprise a feedback mechanism by which excitatory sensory activity drives GABAergic inhibition to maintain circuit homeostasis.

publication date

  • June 2, 2016

Research

keywords

  • Glutamic Acid
  • Neural Inhibition
  • Neurons
  • Presynaptic Terminals
  • Receptors, Metabotropic Glutamate
  • Synapses

Identity

PubMed Central ID

  • PMC4912012

Scopus Document Identifier

  • 84973894725

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2016.05.008

PubMed ID

  • 27263971

Additional Document Info

volume

  • 90

issue

  • 6