During this fiscal year our group identified a major neuronal subpopulation of the PVT that expresses dopamine D2 receptors (D2R+) and whose excitability is significantly enhanced following stress. Importantly, we uncovered that this increase in excitability is the result of a stress-induced reduction in inhibitory synaptic transmission onto D2R+ neurons and requires activation of the D2R. Further assessment of the cellular and molecular mechanisms underlying disinhibition led to the observation that stress is associated with a prominent increase in the extracellular concentration of dopamine in the PVT. Surprisingly, this increase in dopamine was mediated by input from the noradrenergic locus coeruleus (LC). In agreement with this observation, chemogenetic and optogenetic inhibition of LC inputs to the PVT prevented the stress-induced disinhibition of the PVT. Altogether, our results define a cellular and circuit mechanism by which stress impacts the excitability of the PVT. Importantly, as demonstrated by our findings, the circuit and cellular processes uncovered by us shape behavioral and neuroendocrine responses to stress. Additional efforts are currently being placed in contrasting the activity patterns and functional roles of D2R+ and D2R- neurons of the PVT.
| Beas, B Sofia; Wright, Brandon J; Skirzewski, Miguel et al. (2018) The locus coeruleus drives disinhibition in the midline thalamus via a dopaminergic mechanism. Nat Neurosci 21:963-973 |
| Stephenson-Jones, Marcus; Yu, Kai; Ahrens, Sandra et al. (2016) A basal ganglia circuit for evaluating action outcomes. Nature 539:289-293 |
| Do Monte, F H; Quirk, G J; Li, B et al. (2016) Retrieving fear memories, as time goes by…. Mol Psychiatry 21:1027-36 |
