Integration strategies of cortical neurons in the early postnatal neocortex

Over the course of the first three postnatal weeks the cells of the neocortex undergo considerable maturation. My aim was to track some of the changes that occur, to create a detailed electrophysiological study of the postnatal neocortex. This would allow me to better understand the developmental journeys taken by discrete neuronal populations within the maturing network. To this end, I used glutamate uncaging and whole-cell patch-clamp electrophysiology to record from neocortical pyramidal cells and Nkx2-1 derived interneurons located in different cortical layers and regions of the cortex between postnatal days (P) 5-21. In so doing I was able to track the maturation of their intrinsic electrophysiology and synaptic connectivity. The electrophysiological properties of cortical neurons develop markedly over the course of development and there is a gradual emergence of distinct electrophysiological firing types amongst both pyramidal cells and interneurons. In terms of their synaptic inputs pyramidal neurons and interneurons possess unique methods of synaptic integration. Pyramidal neurons show a stereotyped pattern of input maturation, whereby there is a gradual emergence of the mature, canonical pattern of input. This is predicted by translaminar, NMDA receptor mediated inputs at early ages, that likely act as the substrate for the formation of mature AMPA receptor containing synapses. In contrast Nkx2-1 derived interneurons showed no shift in laminar input organization over the course of development, with prominent inputs observed from the earliest ages of the study. However, there seems to be a significant degree of heterogeneity in the organization of these inputs and I provide some insight into this variation. Taken together these findings provide a picture of the connectivity of the early network and using these data I am able to produce a final hypothesis, which shows how interneurons and pyramidal cells may interact to produce the canonical pattern of cortical connectivity