Genetic approaches to elucidating cortical and hippocampal GABAergic interneuron diversity

Abstract

GABAergic interneurons (INs) in the mammalian forebrain represent a diverse population of cells that provide specialized forms of local inhibition to regulate neural circuit activity. Over the last few decades, the development of a palette of genetic tools along with the generation of single-cell transcriptomic data has begun to reveal the molecular basis of IN diversity, thereby providing deep insights into how different IN subtypes function in the forebrain. In this review, we outline the emerging picture of cortical and hippocampal IN speciation as defined by transcriptomics and developmental origin and summarize the genetic strategies that have been utilized to target specific IN subtypes, along with the technical considerations inherent to each approach. Collectively, these methods have greatly facilitated our understanding of how IN subtypes regulate forebrain circuitry via cell type and compartment-specific inhibition and thus have illuminated a path toward potential therapeutic interventions for a variety of neurocognitive disorders.