Inhibitory control of dendritic spikes in CA1 pyramidal cells

The National Institute of Mental Health awarded the University of Pittsburgh $158,960 on January 21, 2027, under the Mental Health Research Grants program (CFDA 93.242) to investigate inhibitory control of dendritic spikes in hippocampal CA1 pyramidal neurons. The project will use optogenetics, two-photon calcium imaging, and voltage imaging to explore how dendrite-targeting somatostatin interneurons regulate dendritic spike dynamics, specifically examining how synaptic inhibition modifies voltage and calcium dynamics across distinct dendritic compartments. The research aims to advance understanding of how inhibitory interneurons control synaptic integration and neural circuit dynamics underlying learning and memory. Performance occurs in Pittsburgh, Pennsylvania, with a period of performance extending from the award date through July 31, 2029. This is a project grant, an assistance type supporting investigator-initiated basic neuroscience research at an eligible research institution.

Abstract

Neurons rely on the precise integration of signals from multiple sources to create accurate representations of sensory information, which are crucial for learning, memory, and behavior. A key mechanism in this process is the dendritic spike, which enables synaptic integration within the dendritic arbor of pyramidal neurons, especially in regions like the hippocampus. Dendritic spikes, such as plateau potentials, sodium and nmda spikes, are known to support memory-related functions like place field formation, but how these spikes are modulated by synaptic inhibition is not well understood. This project will investigate how dendrite-targeting somatostatin interneurons (SST-INS) regulate dendritic spike dynamics in hippocampal CA1 pyramidal neurons. Using optogenetics, two-photon calcium imaging, and voltage imaging, i will explore how SST-INS influence the spatiotemporal properties of plateau potentials and other dendritic spikes across distinct dendritic compartments. Specifically, i aim to determine how inhibitory input modifies voltage and CA2+ dynamics in pyramidal neurons, thereby shaping the functional organization of dendritic compartments during information processing. In addition to addressing the cellular mechanisms underlying dendritic spike regulation, this project will provide insights into how synaptic inhibition governs the segregation or coordination of dendritic compartment activity. These studies will enhance our understanding of the role of inhibitory interneurons in controlling synaptic integration, ultimately advancing our knowledge of neural circuit dynamics that underlie learning and memory.