Identification and characterization of a dopamine neuron subtype with a projection to the amygdala

The neurotransmitter dopamine, produced by midbrain dopaminergic (DA) neurons, influences a spectrum of behaviors including motor, learning, reward, motivation, and cognition. In accordance with its diverse functions, DA dysfunction is prominently implicated in a wide gamut of disorders affecting tens of millions of people, including Parkinson’s disease, schizophrenia, ADHD, addiction and depression. Some of these disorders also include symptoms of severe anxiety. Treatments for these disorders often involve manipulation of DA levels, or DA receptor signaling. However, since current drug regimens target the entire DA system relatively indiscriminately, there is a profound lack of specificity resulting in undesirable outcomes. Towards uncovering novel therapeutic targets of specific aspects of the DA system, we aim to get a better understanding of DA neuron diversity. Elucidating differences between DA subpopulations, may allow for differential pharmacological targeting of subpopulations. As a first step in categorizing DA neurons, we used an unconventional approach to profile single midbrain DA neurons, each for the expression of 96 key genes, using a microfluidic based RT-qPCR array. We found that DA neurons exhibited roughly six distinct molecular barcodes, presumably indicative of six molecularly and functionally distinct DA subtypes. One of these is a population, termed DAS6, located in the periacqeductal gray that, at least preliminarily, appears to project specifically to regions within the extended amygdala. The goal here is to unambiguously define 1. the projection of DAS6 and 2. the involvement of DAS6 neurons in anxiety and fear behaviors. These studies will be the first to define a molecularly discrete DA subtype, with a unique projection and function.