Title | Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Mende M, Fletcher EV, Belluardo JL, Pierce JP, Bommareddy PK, Weinrich JA, Kabir ZD, Schierberl KC, Pagiazitis JG, Mendelsohn AI, Francesconi A, Edwards RH, Milner TA, Rajadhyaksha AM, van Roessel PJ, Mentis GZ, Kaltschmidt JA |
Journal | Neuron |
Volume | 90 |
Issue | 6 |
Pagination | 1189-202 |
Date Published | 2016 Jun 15 |
ISSN | 1097-4199 |
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. |
DOI | 10.1016/j.neuron.2016.05.008 |
Alternate Journal | Neuron |
PubMed ID | 27263971 |
PubMed Central ID | PMC4912012 |
Grant List | T32 DA007274 / DA / NIDA NIH HHS / United States R01 NS083998 / NS / NINDS NIH HHS / United States R01 DA029122 / DA / NIDA NIH HHS / United States R01 DA008259 / DA / NIDA NIH HHS / United States R01 NS078375 / NS / NINDS NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States R01 HL098351 / HL / NHLBI NIH HHS / United States R01 MH082870 / MH / NIMH NIH HHS / United States P01 HL096571 / HL / NHLBI NIH HHS / United States T32 HD060600 / HD / NICHD NIH HHS / United States |