Synaptic Targeting in Hard-Wired Neural Circuits

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****** What are the molecular instructions to hard-wire precise synaptic connections? Only the most critical behaviours for survival are hard-wired into the genome. Behaviours such as breathing and primitive reflexes are not learned, and so the neural circuitry that controls them must be pre-specified using precise molecular instructions. Currently, we know very little about how hard-wired neural circuits are formed. The goal of my research is to identify every molecule necessary and sufficient to wire up a hard-wired neural circuit. My overall hypothesis is that a specific set of cell-surface molecules are required to generate a distinct hard-wired synaptic connectivity. My experimental approach will use single cell RNA sequencing of identified neurons in concert with a systematic characterization of all cell-surface receptors to understand how they can create the neuron's precise wiring pattern. We will then express these molecules in another neuron to re-wire its synaptic connections, alter its function, and thus alter the animal's perception and behavior. This research will be the first demonstration of the exact genetic instructions that can completely hardwire and mis-wire a neural circuit. By understanding how key molecules at the cell surface can produce erroneous synaptic connections, we can investigate ways to correct it. Our proposed work is an important first step towards understanding the molecular instructions underlying innate behaviours.