A Layer 3→5 Circuit in Auditory Cortex That Contributes to Pre-pulse Inhibition of the Acoustic Startle Response.

While connectivity within sensory cortical circuits has been studied extensively, how these connections contribute to perception and behavior is not well understood. Here we tested the role of a circuit between layers 3 and 5 of auditory cortex in sound detection. We measured sound detection using a common variant of pre-pulse inhibition of the acoustic startle response, in which a silent gap in background noise acts as a cue that attenuates startle. We used the Nr5a-Cre driver line, which we found drove expression in the auditory cortex restricted predominantly to layer 3. Photoactivation of these cells evoked short-latency, highly reliable spiking in downstream layer 5 neurons, and attenuated startle responses similarly to gaps in noise. Photosuppression of these cells did not affect behavioral gap detection. Our data provide the first demonstration that direct activation of auditory cortical neurons is sufficient to attenuate the acoustic startle response, similar to the detection of a sound.