Project Overview

The brain is more than the sum of its parts. Truly understanding the brain’s most intricate properties requires both a list of its individual parts, that is a census of the types of neurons it contains, and a map of how these parts are interconnected to form neural circuits. Hundreds of different types of neurons are estimated to compose the mammalian brain, each embedded within complex circuits. The challenge of our generation consists of mapping the connections between these neuronal populations. Current approaches to map circuits have limitations that prevent their widespread adoption or their use in high-throughput experiments. We propose a novel transsynaptic labelling approach that will enable the mapping of interconnected neuronal populations by specific binding of ligand and synthetic receptor across the synaptic cleft. This method will allow genetic targeting of the pre- and post-synaptic components of a circuit, and thus facilitates the investigation of its function. We demonstrate the usefulness of our approach by mapping the circuit of a specific type of dopamine neurons that we hypothesize is involved in reward processing. Through our new transsynaptic labelling approach, this proposal could have a significant impact beyond understanding dopamine circuitry and provide a new toolset to accomplish the daunting task of mapping the brain’s neuronal circuits.