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Precisely timed nicotinic activation drives SST inhibition in neocortical circuits

Item Type:Article
Title:Precisely timed nicotinic activation drives SST inhibition in neocortical circuits
Creators Name:Urban-Ciecko, J. and Jouhanneau, J.S. and Myal, S.E. and Poulet, J.F.A. and Barth, A.L.
Abstract:Sleep, waking, locomotion, and attention are associated with cell-type-specific changes in neocortical activity. The effect of brain state on circuit output requires understanding of how neuromodulators influence specific neuronal classes and their synapses, with normal patterns of neuromodulator release from endogenous sources. We investigated the state-dependent modulation of a ubiquitous feedforward inhibitory motif in mouse sensory cortex, local pyramidal (Pyr) inputs onto somatostatin (SST)-expressing interneurons. Paired whole-cell recordings in acute brain slices and in vivo showed that Pyr-to-SST synapses are remarkably weak, with failure rates approaching 80%. Pharmacological screening revealed that cholinergic agonists uniquely enhance synaptic efficacy. Brief, optogenetically gated acetylcholine release dramatically enhanced Pyr-to-SST input, via nicotinic receptors and presynaptic PKA signaling. Importantly, endogenous acetylcholine release preferentially activated nicotinic, not muscarinic, receptors, thus differentiating drug effects from endogenous neurotransmission. Brain state- and synapse-specific unmasking of synapses may be a powerful way to functionally rewire cortical circuits dependent on behavioral demands.
Keywords:Nicotinic, Somatostatin, Endogenous Neuromodulators, Presynaptic Release, Failure Rate, Barrel Cortex, Sparse Coding, Attention, Rewiring, Glutamatergic, Animals, Mice
Publisher:Cell Press
Page Range:611-625
Date:7 February 2018
Official Publication:https://doi.org/10.1016/j.neuron.2018.01.037
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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