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Microglia-neuronal interactions in Autism Spectrum Disorder (ASD)

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Silva research 4 FImageAutism Spectrum Disorder (ASD) is a range of neurodevelopmental disorders resulting in communication, learning, and behavioral deficiencies. Interestingly, human patients with ASD have altered synaptic density and microglia activation. Through a collaboration with the Kampmann lab at UCSF, we have an interest in investigating the functional role of ASD-risk genes identified from a CRISRRi-based screening from Teter et al., 2024 (Biorxiv). Using CRISPR mutants combined flow cytometer-based engulfment assay and scRNA sequencing technologies, we hope to gain a basic understanding of microglial contributions to ASD.

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Microglial-synaptic interactions during development and neuronal activity

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Zebrafish microglia labelled using transgenic reporter Tg(mpeg1.1:GFP-CAAX): Green show synaptic content Tg(NBT:Synaptophysin:TdT); Red within microglia.

Microglia acutely impact neuronal activity and make activity-dependent contacts with dendritic spines in mammals. This strongly indicates that microglia play a critical role in maintaining healthy neural circuitry, which depends on their activity-dependent interactions with synapses. How these activity-dependent microglial-synapse interactions maintain a healthy circuit though is just beginning to be investigated. We are using genetic, pharmacological, scRNA sequencing, flow cytometry, and imaging approaches to investigate microglial-synaptic interactions during development and neuronal activity to identify novel mechanisms.

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The role of microglia in central nervous system development

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Silva research 1 fimageMicroglia play vital roles in central nervous system (CNS) development, homeostasis, and pathology. In this project, we use our published transcriptomic dataset from regional bulk and whole brain single-cell sequencing of zebrafish microglia to investigate the role of genes critical for microglia function during brain development. Specifically, we are interested in genes enriched in two populations of microglia that were transcriptional and functionally unique namely, neurogenic-associated microglia (NAMs) and synapse-associated microglia (SAMs). Using the power of CRISPR technology in the zebrafish, we mutate candidate genes enriched in these two populations of microglia to understand how they regulate brain development.