Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord

Michael Mende, Emily V. Fletcher, Josephine L. Belluardo, Joseph P. Pierce, Praveen K. Bommareddy, Jarret A. Weinrich, Zeeba D. Kabir, Kathryn C. Schierberl, John G. Pagiazitis, Alana I. Mendelsohn, Anna Francesconi, Robert H. Edwards, Teresa A. Milner, Anjali M. Rajadhyaksha, Peter J. van Roessel, George Z. Mentis, Julia A. Kaltschmidt

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1189-1202
Number of pages14
JournalNeuron
Volume90
Issue number6
DOIs
StatePublished - Jun 15 2016

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Presynaptic Terminals
Glutamic Acid
Spinal Cord
Metabotropic Glutamate Receptors
Brain-Derived Neurotrophic Factor
Interneurons
Sensory Receptor Cells
Synapses
gamma-Aminobutyric Acid
Homeostasis
Population
metabotropic glutamate receptor type 1
glutamate decarboxylase 2
glutamate decarboxylase 1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mende, M., Fletcher, E. V., Belluardo, J. L., Pierce, J. P., Bommareddy, P. K., Weinrich, J. A., ... Kaltschmidt, J. A. (2016). Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord. Neuron, 90(6), 1189-1202. https://doi.org/10.1016/j.neuron.2016.05.008

Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord. / Mende, Michael; Fletcher, Emily V.; Belluardo, Josephine L.; Pierce, Joseph P.; Bommareddy, Praveen K.; Weinrich, Jarret A.; Kabir, Zeeba D.; Schierberl, Kathryn C.; Pagiazitis, John G.; Mendelsohn, Alana I.; Francesconi, Anna; Edwards, Robert H.; Milner, Teresa A.; Rajadhyaksha, Anjali M.; van Roessel, Peter J.; Mentis, George Z.; Kaltschmidt, Julia A.

In: Neuron, Vol. 90, No. 6, 15.06.2016, p. 1189-1202.

Research output: Contribution to journalArticle

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 2016, 'Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord', Neuron, vol. 90, no. 6, pp. 1189-1202. https://doi.org/10.1016/j.neuron.2016.05.008
Mende M, Fletcher EV, Belluardo JL, Pierce JP, Bommareddy PK, Weinrich JA et al. Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord. Neuron. 2016 Jun 15;90(6):1189-1202. https://doi.org/10.1016/j.neuron.2016.05.008
Mende, Michael ; Fletcher, Emily V. ; Belluardo, Josephine L. ; Pierce, Joseph P. ; Bommareddy, Praveen K. ; Weinrich, Jarret A. ; Kabir, Zeeba D. ; Schierberl, Kathryn C. ; Pagiazitis, John G. ; Mendelsohn, Alana I. ; Francesconi, Anna ; Edwards, Robert H. ; Milner, Teresa A. ; Rajadhyaksha, Anjali M. ; van Roessel, Peter J. ; Mentis, George Z. ; Kaltschmidt, Julia A. / Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord. In: Neuron. 2016 ; Vol. 90, No. 6. pp. 1189-1202.
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