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Nat Neurosci. 2017 Jan;20(1):62-71. doi: 10.1038/nn.4436. Epub 2016 Oct 31.

Parallel processing by cortical inhibition enables context-dependent behavior.

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Skirball Institute, Neuroscience Institute, Departments of Otolaryngology, Neuroscience and Physiology, New York University School of Medicine, New York, New York, USA.
Center for Neural Science, New York University, New York, New York, USA.
Center for Theoretical Neuroscience, Department of Neuroscience, Swartz Program in Theoretical Neuroscience, Kavli Institute for Brain Science, Columbia University, New York, New York, USA.


Physical features of sensory stimuli are fixed, but sensory perception is context dependent. The precise mechanisms that govern contextual modulation remain unknown. Here, we trained mice to switch between two contexts: passively listening to pure tones and performing a recognition task for the same stimuli. Two-photon imaging showed that many excitatory neurons in auditory cortex were suppressed during behavior, while some cells became more active. Whole-cell recordings showed that excitatory inputs were affected only modestly by context, but inhibition was more sensitive, with PV+, SOM+, and VIP+ interneurons balancing inhibition and disinhibition within the network. Cholinergic modulation was involved in context switching, with cholinergic axons increasing activity during behavior and directly depolarizing inhibitory cells. Network modeling captured these findings, but only when modulation coincidently drove all three interneuron subtypes, ruling out either inhibition or disinhibition alone as sole mechanism for active engagement. Parallel processing of cholinergic modulation by cortical interneurons therefore enables context-dependent behavior.

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