Our laboratory studies social memory, the underlying hippocampal microcircuits, and the participation and relationships among adult-born granule cells, perineuronal nets, and microglia. The ultimate goal of our work is to understand how these cells and their cellular or extracellular structures work collectively to impact hippocampal microcircuitry and social memory.
Social impairments, including deficits in social memory, are a feature of many devastating conditions such as autism spectrum disorder, major depression, schizophrenia, and Alzheimer's disease. Several hippocampal subregions and their connections to each other have been identified as important for social memory. Thus, our lab uses behavioral, histological, pharmacologic, environmental, transgenic, viral, chemogenetic, and in vivo electrophysiological methods to investigate the role of adult-born granule cells, microglia, and perineuronal nets, their interactions, and how they shape hippocampal social memory circuitry.
Current Projects
Adult-born granule cells
Newly generated adult-born granule cells and their axons immunolabed with 3R-Tau (red). Adapted from Cope et al. (2021).
Granule cells of the dentate gyrus, a neuronal cell population known to innervate multiple cellular targets in the hilus, dentate gryus, CA3 and CA2, are continuously generated in the adult brain, a process known as adult neurogenesis. Adult neurogenesis has been associated with several of the cognitive functions associated with the hippocampus, including spatial memory, contextual fear memory, and social memory. Indeed, our published studies have shown that pharmacogenetic ablation of adult neurogenesis impairs social memory. We have found reduced adult-born granule cell numbers and fewer axons from adult-born granule cells in the CA2 of mouse models of social dysfunction. Ongoing studies are exploring how adult-born granule cells participate in social memory traces.
Perineuronal nets
Perineuronal nets (green) labeled with plant-based lectin WFA surrounding PCP4-labeled CA2 neurons (red). Adapted from Cope et al. (2021).
Perineuronal nets are specialized extracellular matrix structures that enwrap some types of neurons and limit their plasticity. While perineuronal nets typically surround inhibitory interneurons in the hippocampus, the CA2 is unique in that it has a high abundance of perineuronal nets surrounding the excitatory pyramidal cells. Our published studies have found that CA2 perineuronal nets are essential for social memory and that atypical perineuronal nets contribute to social memory impairments in a mouse model of social dysfunction. Ongoing studies are exploring perineuronal net components and whether atypical CA2 perineuronal nets are causally linked to other aspects of hippocampal structure and function.
Microglia
GFP-labeled microglia (green) from the mouse dentate gyrus.
Microglia, the brain’s resident immune cells, shape neural circuits during healthy brain development and have been shown to be important for hippocampal-dependent cognition. Our published studies have found that microglia are responsible for cognitive decline and dendritic spine loss induced by obesity. Ongoing studies are examining the role of microglia in the development and maintenance of synaptic connections and circuit activity related to social memory.