The genetic basis of the first connections in the brain

Presenter(s): Anisha Adke – Biology

Faculty Mentor(s): Adam Miller

Poster 46

Research Area: Biology

Funding: Vice President for Research and Innovation (VPRI) Undergraduate Fellowship, UROP Mini-grant

An estimated 100 billion neurons form the human brain, equal to the number of stars in our galaxy. Nervous system function emerges from connections, or synapses, between these neurons, which are either electrical or chemical. The synapses form a wired circuit that emerges over development as directed by an organism’s genetic code. The first synapses that form are critical to normal circuit wiring, as they lay the foundation upon which mature circuits are built. Research has shown that these first synapses are electrical, but it is unknown which genes are responsible for the connections. This project aims to identify the genes required for the first synapses and investigate their roles from a molecular, circuit, and behavioral standpoint. This will provide a critical understanding of nervous system wiring, as genetic defects that alter normal circuit wiring are linked to neurodevelopmental disorders such as autism and schizophrenia.
To explore the genes responsible for electrical synapses, we examined the first spinal cord circuits that form in zebrafish. We identified genes-of-interest using RNAseq and are finding when, where, and how these genes control the formation of the first synapses, analyzing them for neural network and behavioral changes. Preliminary behavioral analysis suggests that the gene Cx46.8 is involved in early circuit formation, while mutations in Cx35.1, Cx34.1, Cx35.5, Cx34.7, and Cx43.4 show no visible disruption. Future work using RNA in situ hybridization will characterize Cx46.8 localization, allowing for a better understanding of where the gene is at work. We are also using fluorescent calcium indicators to characterize the mutations and the resulting disruptions to circuit wiring in order to understand the roles of the genes in early electrical synapse formation.

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