Pyramidal cells are the principal neurons of the hippocampus and neo-cortex, and are among the most important neuronal processing elements in the brain. However, the rules governing synaptic integration in pyramidal cells remain poorly understood. In this work we propose to carry out a series of tightly linked experimental and modeling studies to gain further insight into pyramidal cell function. Experimental studies in hippocampal and neo-cortical slices will investigate how synaptic inputs delivered to multiple dendritic locations combine forces to generate overall cell responses. These experiments will bring together a variety of methods to gain unprecedented control over the experimental situation, including a novel setup for multi-site UV-laser un-caging of glutamate and GABA, focal synaptic stimulation using multiple extra-cellular electrodes, calcium fluorescence imaging, dual intracellular recordings, and local and bath applied pharmacological blockers. Modeling studies will be run in the closest possible correspondence to the experimental work, and will culminate in the development and public release of state-of-the-art detailed biophysical models of a hippocampal and a neo-cortical pyramidal cell. These models will be immediately useful in both the experimental and modeling communities. Finally, our overarching objective is to arrive at an appropriate simplifying abstraction for the individual pyramidal neuron. ? ?
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