RAIDAR: A tool for examining neurons through their connections

Neurons form the basic functional unit of our nervous systems. While we have a litany of tests and procedures to understand a single neuron, we have fewer that allow us to visualize or confirm circuits, sequences of neurons working together, and none that allow us to manipulate neurons in the context of a specific circuit in living, freely behaving animals. Achieving dual specificity where a specific neuron population of interest can be manipulated while knowing the neuron it directly connects to will allow us to achieve a deeper understanding of the brain: not just of individual neurons, but of how these neurons function in the circuits they form.

In this work we introduce RAIDAR, a new tool for achieving the aforementioned dual specificity in the brain. We show this through manipulating part of a specific brain circuit. This circuit was found to be important for fibroblast growth factor 21 (FGF21), a liver-derived hormone, to reduce alcohol intake. Without the expression of a required co-receptor for FGF21 in the first population of neurons in the circuit, FGF21 application is unable to reduce alcohol intake in living animals. RAIDAR enabled us to specifically activate that first population of neurons in animals in the context of a downstream population, resulting in a reduction of alcohol intake similar to that driven by FGF21. RAIDAR allows us to ask questions about portions of neuronal circuits in living animals which we couldn’t before, broadening the horizon of what can be known about our nervous system.