Network-Level Control of Frequency Tuning in Auditory Cortex

Lateral inhibition is a fundamental circuit operation that sharpens the tuning properties of cortical neurons. This operation is classically attributed to an increase in GABAergic synaptic input triggered by non-preferred stimuli. Here we use in vivo whole-cell recording and two-photon Ca²⁺ imaging in awake mice to show that lateral inhibition shapes frequency tuning in primary auditory cortex via an unconventional mechanism: non-preferred tones suppress both excitatory and inhibitory synaptic inputs onto layer 2/3 cells ("network suppression"). Moreover, optogenetic inactivation of inhibitory interneurons elicits a paradoxical increase in inhibitory synaptic input. These results indicate that GABAergic interneurons regulate cortical activity indirectly via the suppression of recurrent excitation. Furthermore, the network suppression underlying lateral inhibition was blocked by inactivation of somatostatin-expressing interneurons (SOM cells), but not parvalbumin-expressing interneurons (PV cells). Together, these findings reveal that SOM cells govern lateral inhibition and control cortical frequency tuning through the regulation of reverberating recurrent circuits.