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. •Frequency tuning in auditory cortex of mice is shaped by lateral inhibition•Lateral inhibition is due to the suppression of recurrent excitation•Somatostatin-expressing interneurons trigger network suppression•Auditory cortex operates as an inhibition-stabilized network (ISN) Kato et al. show that lateral inhibition shapes frequency tuning in primary auditory cortex via an unconventional mechanism: non-preferred stimuli suppress recurrent excitation. Somatostatin-expressing interneurons are critical for triggering this indirect form of cortical inhibition.