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キーワード:
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要旨:
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 mGluR1b 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.
