Anatomical-functional analysis of the spatially restricted Transient receptor vanilloid-1 (Trpv1)-positive domain within the medial hypothalamic-mesencephalic area

The distribution pattern and functional role of brain neurons expressing the Transient receptor vanilloid-1 (Trpv1) gene, which in the sensory nervous system regulates body temperature, heat and pain, have remained obscure. Two studies using both in situ hybridization to detect endogenous Trpv1 mRNA and a floxed reporter allel in Trpv1-Cre mice, have detected sparse expression in the caudal aspect of the hypothalamus and the ventral tegmental area of the midbrain. This area has during recent years been associated with aversion processing via glutamatergic neurons expressing the Vesicular glutamate transporter 2 (Vglut2) gene. Glutamatergic neurons of this area thus seem to be selectively correlated with aversion, while dopaminergic neurons in the ventral midbrain have long been associated with reward processing. A previous study from our laboratory found that the Trpv1-positive neuronal population consisted of both glutamatergic and dopaminergic neurons. It was therefore of particular interest to study this population further. Would this small but distinct hypothalamic-mesencephalic neuronal group of neurons regulate any specific type of behaviour if selectively activated? The results presented show that Trpv1 mRNA is primarily detected at the perinatal stage forming a band of neurons stretching from the posterior hypothalamus through to, and including, the ventral tegmental area. In the mature mouse, application of optogenetic constructs to the Trpv1-Cre-positive population enabled the analysis of both projection pattern and behavioural role of the Trpv1 neurons. These rare neurons, forming a hypothalamic-mesenecphalic continuum, project to several areas of the limbic system including the hippocampus, septum, nucleus accumbens and the preoptic area. When optogenetically activated, Trpv1-Cre mice show normal movements in the open field test, but display progressive avoidance behaviour in an optogenetic real-time place preference test. The results identify a new neur