Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord
| Autor: | Josephine L. Belluardo, Alana I. Mendelsohn, Peter van Roessel, Julia A. Kaltschmidt, Joseph P. Pierce, George Z. Mentis, Anna Francesconi, Zeeba D. Kabir, Robert H. Edwards, Kathryn C. Schierberl, Praveen K. Bommareddy, Teresa A. Milner, Anjali M. Rajadhyaksha, Jarret A.P. Weinrich, John G. Pagiazitis, Michael Mende, Emily V. Fletcher |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Sensory Receptor Cells Models Neurological Presynaptic Terminals Glutamic Acid Biology Receptors Metabotropic Glutamate Inhibitory postsynaptic potential Article gamma-Aminobutyric acid Mice 03 medical and health sciences 0302 clinical medicine Interneurons medicine Animals gamma-Aminobutyric Acid Neurons Brain-derived neurotrophic factor Glutamate Decarboxylase Brain-Derived Neurotrophic Factor General Neuroscience Glutamate receptor Neural Inhibition 030104 developmental biology Spinal Cord Metabotropic glutamate receptor Synapses Vesicular Glutamate Transport Protein 1 Excitatory postsynaptic potential Synaptic signaling Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuron |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2016.05.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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