Direct cellular reprogramming is a powerful new tool for regenerative medicine. In efforts to understand and treat Parkinson's Disease (PD), which is marked by the degeneration of dopaminergic neurons in the midbrain, direct reprogramming provides a valuable new source of these cells. Astrocytes, the most plentiful cells in the central nervous system, are an ideal starting population for the di...

Evidence from electrophysiological studies has suggested an inhibitory interaction between GABAergic neurons in substantia nigra pars reticulata and dopaminergic neurons in pars compacta. However, that this inhibitory interaction is due to a projection from pars reticulata to pars compacta has never been demonstrated directly, nor has the GABAergic neuron that mediates the interaction been iden...

Obesity causes hyperleptinemia. We have previously shown that D2 receptor-mediated inhibition of ventral tegmental area (VTA) dopaminergic neurons is attenuated in diet-induced mice with obesity. Consequently, we hypothesized that high concentrations of serum leptin during obesity might modulate D2 receptor-mediated effects on VTA dopaminergic neurons. To investigate our hypothesis, we examined...

Midbrain dopaminergic neurons are highly heterogeneous. They differ in their connectivity and firing patterns and, therefore, in their functional properties. The molecular underpinnings of this heterogeneity are largely unknown, and there is a paucity of markers that distinguish these functional subsets. In this paper, we report the identification and characterization of a novel subset of midbr...

–A subpopulation of inactive or ‘‘silent’’ dopaminergic neurons has been reported to exist in vivo in rat substantia nigra, comprising up to 50% of nigral dopaminergic neurons. The existence of this large proportion of silent neurons has been inferred from various experimental manipulations, but never demonstrated directly. In the present study, striatal or medial forebrain bundle stimulation w...

It is known that the posterior ventral tegmental area (p-VTA) differs from the anterior VTA (a-VTA) in that rats learn to self-administer ethanol into the p-VTA, but not into the a-VTA. Because activation of VTA dopaminergic neurons by ethanol is a cellular mechanism underlying the reinforcement of ethanol consumption, we hypothesized that ethanol may exert different effects on dopaminergic neu...

Lateral habenula (LHb) neurons convey aversive and negative reward conditions through potent indirect inhibition of ventral tegmental area (VTA) dopaminergic neurons. Although VTA dopaminergic neurons reciprocally project to the LHb, the electrophysiological properties and the behavioral consequences associated with selective manipulations of this circuit are unknown. Here, we identify an inhib...