Cellular interactions underlying organization of cortical circuits

A major question in neuroscience is how appropriate connections are formed when the brain develops and how these connections are modified with experience. It is well established that neural circuits are fine-tuned by experience during 'critical periods' i n early postnatal life. In the visual system, closing one eye for only a few days during the critical period leads to decrease in the cortical representation of the deprived eye, and long lasting vision impairment despite a healthy eye. A long-standing qu estion for our understanding of the brain's remarkable adaptive capacity is to what extent the brain's plasticity depends on physical rearrangement of the connections between nerve cells. Previously, it was only possible to study morphological effects of plasticity changes post mortem. With the advancement of two-photon laser scanning microscopy and genetic labeling of neurons, activity-dependent plasticity can be observed in neurons in vivo as an increased rate in the turnover of dendritic spines. Hither to, such studies have mainly been conducted in adult mice and little is known about the reorganization of connections between single neurons in vivo during the critical period. Furthermore, it remains elusive how these anatomical changes are reflected in physiological changes of the very same neurons. I propose to identify the changes in the cortical circuit responsible for rapid, activity-dependent plasticity in the visual cortex of mice during the critical period. These questions will be addressed by in ducing activity-dependent plasticity experimentally, and repeatedly monitor morphological and functional changes of identified cells of different cell classes. Due to technical limitations, the majority of in vivo studies on visual cortex have been done in animals under anesthesia. Thus our current understanding of visual cortical processing is founded on the assumption that cortical processing in the anesthetized state mirrors that of the awake, behaving animal. I will therefore develop techniques that will enable chronic imaging of subcellular structures and function in the awake animal. The significance of my research lies in the likelihood that the developing visual cortex will be a fruitful system for revealing the mechanisms of neocortical plastici ty and function.