Development and plasticity of neural circuits

Half a century ago, Donald Hebb postulated correlated activity-induced synaptic strengthening as a mechanism for the formation of functional neural circuits in the brain. Recent studies in the field have further indicated that temporally correlated activity leads to both synaptic strengthening (LTP) and weakening (LTD) depending on the precise timing of pre- and postsynaptic spikes. Moreover, activity-induced synaptic modification appears to be able to ìspreadî to specific neighboring synapses. What cellular processes underlie the stringent temporal specificity of synaptic plasticity? What molecular signals mediate the specific spread? How does such spatio-temporal specificity manifest itself in activity-instructed development and remodeling of neural circuits that form the basis of cognition, learning and memory?

Research in Dr. Bi’s laboratory aims at addressing these and other related questions at two different levels of organization. At the cellular level, hippocampal and cortical cultures are used to study the modification of identified single synapses by correlated activities, as well as the spread of such modification to neighboring sites. The goal is to characterize a complete set of rules of activity-dependent synaptic modification and to elucidate the underlying cellular mechanisms. At the circuitry level, brain slice and cultures are used to investigate how the cellular rules may influence the activity-dependent development and remodeling of neural circuits. In collaboration with theoreticians, the experimental findings are implemented in neural network models to gain further insights into their functional implications.

Trainees in the laboratory have the opportunity to engage in a variety of projects and are encouraged to combine multiple experimental and analytical approaches. Basic techniques include cell and slice culture, gene transfection, whole-cell patch-clamp recording, real-time live fluorescence imaging, and computer simulation.

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