TitleSensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord.
Publication TypeJournal Article
Year of Publication2016
AuthorsMende 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
JournalNeuron
Volume90
Issue6
Pagination1189-202
Date Published2016 Jun 15
ISSN1097-4199
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.

DOI10.1016/j.neuron.2016.05.008
Alternate JournalNeuron
PubMed ID27263971
PubMed Central IDPMC4912012
Grant ListT32 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