Consequences of chronic reduction of cortical inhibition

Abstract

The auditory cortex plays a key role in auditory learning, speech perception, auditory attention, and cognitive analysis of sound. Like other neocortices, it consists of a layered network of excitatory cells and inhibitory interneurons. The inhibitory interneurons comprise only 15–20% of neocortical neurons but are much more diverse than the excitatory cells. Many distinct types of inhibitory interneurons have been identified based on differences in morphology, physiology, connectivity, and gene expression (1). These different interneuron types may have specialized functions within cortical circuits (2, 3). Moreover, certain brain disorders seem to be associated with dysfunction in particular interneuron classes. For example, schizophrenia appears to be linked to specific changes in cortical circuitry involving parvalbumin (PV)-positive interneurons (4); conversely, aging may have a disproportionate impact on somatostatin (SOM)-positive interneurons (5). How do chronic reductions in particular inhibitory interneuron populations affect cortical processing? In PNAS, Seybold et al. (6) address this question, exploring the effects of chronic, late-onset reduction in the number of dendrite-targeting interneurons (DTIs) in the auditory cortex of mice with a conditional KO of the gene Dlx1.