Pathway-specific regulation of the paraventricular thalamic nucleus in depressive-like behavior

Bipolar disorder is one of major psychiatric disorders afflicting about 1% of the world population. While genetic factors have been increasingly recognized as contributing to the disorder, the underlying etiology of bipolar disorder, such as associated brain regions and cellular pathology, are yet to be elucidated. Our previous studies using a genetic bipolar disorder animal model indicated potential role of the paraventricular thalamic nucleus (PVT) in recurrent depressive-like episodes that exhibit phenotypic similarity to the depression phase of bipolar disorder. Notably, chronic activation of PVT induced spontaneous depressive-like episodes. Primary projection targets of PVT include the nucleus accumbens (NAc) and basolateral amygdala (BLA). However, the circuit involving PVT that causes recurrent depressive-like episodes remains to be addressed. Thus, we activated the PVT neurons projecting to NAc or BLA selectively to investigate their roles in eliciting depressive-like episodes. We found that activation of the PVT-NAc pathway induced depressive-like episodes, as measured by reduced wheel running activity in mice. In contrast, wheel running activity was unaffected by activation of the PVT-BLA pathway. These results highlight the critical involvement of PVT-NAc circuit in mood regulation and suggest it may be a key neural substrate underlying depressive-like episodes in bipolar disorder.