Sexual congruency in the connectome and translatome of VTA dopamine neurons

Abstract

The ventral tegmental area (VTA) dopamine system is important for reward, motivation, emotion, learning, and memory. Dysfunctions in the dopamine system are linked to multiple neurological and neuropsychiatric disorders, many of which present with sex differences. Little is known about the extent of heterogeneity in the basic organization of VTA dopamine neurons with regard to sex. Here, we characterized the cell-specific connectivity of VTA dopamine neurons, their mRNA translational profile, and basic electrophysiological characteristics in a common strain of mice. We found no major differences in these metrics, except for differential expression of a Y-chromosome associated mRNA transcript, Eif2s3y, and the X-linked, X-inactivation transcript Xist. Of note, Xist transcript was significantly enriched in dopamine neurons, suggesting tight regulation of X-linked gene expression to ensure sexual congruency. These data indicate that the features that make dopamine neurons unique are highly concordant and not a principal source of sexual dimorphism.

Determination of circuit-specific morphological adaptations in ventral tegmental area dopamine neurons by chronic morphine

“…We found no significant difference between the soma size of VTA DA neurons (PN subregion) of male and female DA-Cre mice (Fig. 1e, student t-test, t (13) = 0.007953, p = 0.99) consistent with observations that there are no sex differences in the basal electrophysiological properties, connectome or translatome of VTA DA neurons [10]. Thus, in subsequent experiments we combined data from males and females.

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Neural and Hormonal Control of Sexual Behavior

“…Activity of the mesolimbic dopamine system, namely dopamine release by the VTA into the nucleus accumbens (NAc), is thought to signal motivational salience of a stimulus, encode reward predictions, and facilitate reinforcement learning ( 162 ). The VTA receives significant input from the MPOA, MeA, and BNST in both sexes ( 163 ). Numerous groups have reported elevated dopamine release in the NAc upon presentation of a potential mate and during active mating in both males and females ( 164-172 ).…”

Divergent medial amygdala projections regulate approach–avoidance conflict behavior

“…We recently identified the MeA as a brain region activated in response to stimulation of midbrain dopamine neurons 10 . The midbrain dopamine system plays an essential role in reward learning, motivation, fear learning and avoidance of conditioned stimuli 11 .…”

“…This anatomical association suggests that the MeA may be functionally involved in dopamine-dependent behaviors. Given the role of the MeA in regulating innate defensive responses 17 , along with the observation that dopamine neurons of the midbrain are connected to this striatopallidal-like structure 10 , we hypothesized that dopamine receptive neurons in this region would likely contribute to innate approach and avoidance behavior. We identified dopamine receptive neurons in the MeA that express D1R and are strongly biased in their localization to the MeApv.…”