The development, circuit, and function of cortical interneurons

Abstract

GABAergic cortical interneurons play a crucial role in regulating cortical function through inhibition. Despite their relatively small numbers, these neurons are highly diverse in terms of molecular types and are vital for controlling the activity of neuronal circuits. However, the function and activity of these neurons, particularly the LAMP5+ cortical interneurons (also known as neurogliaform cells), are not well understood, and the development of inhibitory circuits remains to be fully elucidated. In this thesis, I describe my efforts to investigate the circuits and functions of cortical interneurons both in adults and during circuit development. In Chapter 1, I provide a general overview of cortical interneurons and inhibitory circuits, including a focused review on cortical layer 1, reproduced from published material. In Chapter 2, I discuss genetic strategies to selectively target cortical neurogliaform cells and present evidence that these interneurons modulate state-dependent cortical activity and exhibit layer-specific activity in the primary visual cortex. Chapter 3 describes a series of experiments demonstrating the requirement of bottom-up sensory inputs for the establishment of top-down inputs onto cortical layer 1 interneurons. In Chapter 4, I detail findings on how developing inhibitory synapses are pruned by microglia via GABA signaling. Finally, in Chapter 5, I conclude with a discussion on the development, circuits, and functions of cortical interneurons and offer insights into possible future research directions.