Sunday, August 2, 2015

Kishore Kuchibhotla: June 17th

Synaptic and circuit logic of task engagement in auditory cortex

Animals can adjust their behavior based on immediate context. A pedestrian will move rapidly away from traffic if she hears a car honk while crossing a street – executing a learned sensorimotor response. The same honk heard by the same pedestrian will not elicit this response if she is seated on a nearby park bench. How do neural circuits enable this type of behavior and flexibly encode the same stimuli in different contexts? Here we dissect the natural activity patterns of the same auditory stimuli in different contexts and show that attentional demands of a behavioral task transform the input-output function in auditory cortex via cholinergic modulation and local inhibition. Mice were trained to perform a go/no-go operant task in response to pure tones in one context (“active context”) and listen to the same pure tones but execute no behavioral response in another context (“passive”). In the active context, tone-evoked responses of layer 2/3 auditory cortical neurons were broadly suppressed when compared to the passive context but a specific sub-network showed increased activity. Neural responses shifted within 1-2 trials after the context switched. Whole-cell voltage clamp recordings in behaving mice showed larger context-dependent changes in inhibition than excitation, and the two sets of inputs sometimes changed in opposing directions. Attentional demands appear to reduce the necessity of co-tuned synaptic inputs, an otherwise established requirement in passive brain states. Task engagement elevated tone-evoked responses in PV-positive interneurons and suppressed VIP-positive interneuron responses, implicating both in the context-dependent changes to layer 2/3 output. Global behavioral context, in this case the attentional demands in the active context, was relayed to the auditory cortex by the nucleus basalis, as revealed by axonal calcium imaging of NB cholinergic projections. Thus, local synaptic inhibition gates long-range cholinergic modulation from NB to rapidly alter auditory cortical output, temporarily removing the requirement of co-tuned excitatory and inhibitory inputs, and improving perceptual flexibility.

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