A fundamental question in neuroscience is to understand how different sets of neurons in a network combine or integrate their various inputs, and how both the pattern of inputs and the resulting outputs are related to behavior. Novel, even unprecedented, experimental methods have been and are being developed with which to image or record from large numbers of distributed neurons but understanding the integration step can be difficult since inputs and outputs are generally distributed over many millimeters, and it is very difficult to record from both simultaneously, especially so in a behaving animal. This project will combine experimental and computational methods to elucidate such synaptic integration in pyramidal neurons associated with mammalian spatial navigation in awake, behaving animals. The imaging data acquired from awake behaving mice will be made available to other groups and the full results will serve as a model for other research concerned with the integration of inputs in networks of neurons. The computational models will be made available on the ModelDB database and will be a resource to others working to understand other aspects of functionality in this brain region. Furthermore, the work will involve a close collaboration between experimental and computational research groups, thus giving postdoctoral fellows and graduate students cross-disciplinary research training.
In pyramidal neurons of the hippocampus, the large dendritic tree constitutes an elaborate network of branching processes involving tens of thousands of excitatory synapses containing a variety of voltage-gated ion channels. The pattern of synaptic inputs impinging upon the dendritic arbor and the degree to which these inputs are processed by it to drive place field firing (i.e., firing correlated with spatial location) during behavior are currently unknown. The goals of the project are first to 1) develop improved computational models of dendritic place cell firing constrained by current imaging data and 2) establish new experimental techniques to image the inputs to pyramidal cells in the dendritic tree, at single spine resolution, during place field firing. Together the experiments and models will be used to 3) determine the degree to which local dendritic processing is involved in place cell firing. The proposed experiments will allow for the construction of significantly improved models of hippocampal function and the models will provide a framework within which to understand activity recorded at a local level in the dendritic tree and assemble a comprehensive picture of dendritic processing across the whole arbor.
