Functional dynamics, organization and plasticity of place cell dendritic spines

While the firing patterns of numerous types of neurons have been extensively measured in behaving animals, surprisingly little is known about the synaptic inputs and cellular mechanisms that cause the neurons to fire during behaviors. Experiments probing these firing mechanisms have traditionally been performed in reduced preparations (e.g. brain slices); however the experiments proposed here, will instead combine virtual reality (VR) with advanced optical and genetic tools to measure synaptic input and dendritic integration mechanisms in behaving mice. Specifically, I will first determine the spatiotemporal pattern of inputs that drive hippocampal place cell firing. I will then establish the changes in synaptic strength and presynaptic activity associated with encoding new spatial memories by observing spine structural and functional changes during a remapping paradigm. With support from the McKnight Foundation, my studies will ultimately bridge two large, but not yet connected areas of neuroscience research: electrode recording studies in behaving rodents that characterize firing patterns of place cells and brain slice experiments used to study firing and plasticity mechanisms in the same neurons. The results are expected to fundamentally change our understanding of the neuronal computations used to transform synaptic inputs into firing outputs during behavior.