Chronic reduction in inhibition reduces receptive field size in mouse auditory cortex

Abstract

Inhibitory interneurons regulate the responses of cortical circuits. In auditory cortical areas, inhibition from these neurons narrows spectral tuning and shapes response dynamics. Acute disruptions of inhibition expand spectral receptive fields. However, the effects of long-term perturbations of inhibitory circuitry on auditory cortical responses are unknown. We ablated ?30% of dendrite-targeting cortical inhibitory interneurons after the critical period by studying mice with a conditional deletion of Dlx1. Following the loss of interneurons, baseline firing rates rose and tone-evoked responses became less sparse in auditory cortex. However, contrary to acute blockades of inhibition, the sizes of spectral receptive fields were reduced, demonstrating both higher thresholds and narrower bandwidths. Furthermore, long-latency responses at the edge of the receptive field were absent. On the basis of changes in response dynamics, the mechanism for the reduction in receptive field size appears to be a compensatory loss of corticocortically (CC) driven responses. Our findings suggest chronic conditions that feature changes in inhibitory circuitry are not likely to be well modeled by acute network manipulations, and compensation may be a critical component of chronic neuronal conditions.