Nonoverlapping sets of synapses drive on responses and off responses in auditory cortex.

Neurons in visual, somatosensory, and auditory cortex can respond to the termination as well as the onset of a sensory stimulus. In auditory cortex, these off responses may underlie the ability of the auditory system to use sound offsets as cues for perceptual grouping. Off responses have been widely proposed to arise from postinhibitory rebound, but this hypothesis has never been directly tested. We used in vivo whole-cell recordings to measure the synaptic inhibition evoked by sound onset. We find that inhibition is invariably transient, indicating that off responses are not caused by postinhibitory rebound in auditory cortical neurons. Instead, on and off responses appear to be driven by distinct sets of synapses, because they have distinct frequency tuning and different excitatory-inhibitory balance. Furthermore, an on-on sequence causes complete forward suppression, whereas an off-on sequence causes no suppression at all. We conclude that on and off responses are driven by largely nonoverlapping sets of synaptic inputs.