Elucidating mechanisms of active dendritic integration in vivo

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Neural circuitry processes information at the cellular level by filtering, amplifying, and integrating electrical signals generated and modulated by synaptic input and voltage-gated mechanisms. This project focuses on uncovering the underpinnings of such processes using electrophysiology, two-photon imaging, and optogenetics. The key aim is to understand the role of neuronal dendrites in processing information during in vivo circuit activity. Dendrites can fire regenerative electrical spikes much like axons, and this potentially provides a critical aspect to information processing at the cellular level. How such an active mechanism is engaged and plays a functional role in a behaving animal remains unclear. By directly recording intracellular electrical activity from fine distal dendrites and their parent somas during sensory processing in vivo, along with two-photon imaging of calcium dynamics at synaptic inputs and dendrites, we seek to understand how active dendritic mechanisms contribute to synaptic integration, and how their modulation affects sensory integration. In this study, we will address the following questions in vivo: 1) What is the relationship between dendritic synaptic inputs and dendritic spiking, 2) how effective are dendritic spikes in triggering axonal action potentials, and 3) what is the functional role of dendritic spikes in sculpting the receptive field properties of neuronal output. Findings from the project will both further our understanding of the fundamental mechanisms of cellular information processing and provide a foothold to decipher how neural circuitry is affected in conditions such as Alzheimer’s Disease and other neurophysiological disorders.