Mapping of Cannabinoid Type 1 Receptor Inputs into Dopamine Neurons of the Ventral Tegmental Area

Abstract

The mesolimbic dopamine (DA) pathway is critically involved in reward-seeking and appetitive behaviors. It originates in the ventral tegmental area (VTA) and provides DA innervation to terminal regions. Impaired DA transmission is a hallmark of schizophrenia, depression and drug abuse. The activity of DAergic cells is potently modulated by the endocannabinoid system (ECS). The ECS influences neuronal activity through presynaptic inhibition of neurotransmitter release. The cannabinoid type 1 receptor (CB1R) is the main receptor involved in this signaling pathway. Here, we identify inputs to VTA DA neurons that express CB1R mRNA. Using a series of viral vectors, we first identified monosynaptic inputs to DA neurons in the VTA. We then performed a combination of radioactive in situ hybridization and immunohistochemistry to label monosynaptic inputs expressing CB1R mRNA. Our results identify a population of VTA DA afferent neurons arising from the dorsal raphe nucleus that signal through the ECS.