Development of the translaminar circuits in the mouse cortex

Abstract

The elaborated connections among cortical neurons form the cortical circuits, which are essential mechanisms underlying various cortical functions such as sensory perception, motor control, and other cognitive functions. The cortical circuits are composed of excitatory neurons and GABAergic interneurons. Excitatory neurons send excitatory connections to cortical neurons, while inhibitory neurons send inhibitory connections. Building the neural circuits is no easy task involving complex genetic programs and the influence of the environment through sensation. Malformation of the cortical circuits during development is implicated in causing neurological disorders, but our knowledge about the developmental process is scarce. The work in this dissertation uses in vitro electrophysiology in brain slices from transgenic mice to investigate how the excitatory connections onto GABAergic interneurons in the primary auditory cortex develop during the first two postnatal weeks. Furthermore, this dissertation explores the mechanisms that could regulate the early development of the cortical circuits by testing the requirement of sensory epithelium and N-methyl-D-aspartate receptors (NMDARs) in the early postnatal development of the neural circuits in the primary sensory cortex and temporal association cortex (TeA), respectively. Results from these studies fill crucial gaps in our understanding of how GABAergic interneurons are integrated into the cortical circuits and highlight the importance of sensory epithelium in the normal development of excitatory connections onto cortical GABAergic interneurons. My results also showed impaired development of GABAergic connections onto excitatory neurons lacking functional NMDARs in the TeA, suggesting an essential role of NMDARs for the early development of inhibitory circuits in the cortex.