@article {DolzaniENEURO.0229-16.2016, author = {Samuel D. Dolzani and Michael V. Baratta and Jose Amat and Kara L. Agster and Michael P. Saddoris and Linda R. Watkins and Steven F. Maier}, title = {Activation of a Habenulo{\textendash}Raphe Circuit Is Critical for the Behavioral and Neurochemical Consequences of Uncontrollable Stress in the Male Rat}, volume = {3}, number = {5}, elocation-id = {ENEURO.0229-16.2016}, year = {2016}, doi = {10.1523/ENEURO.0229-16.2016}, publisher = {Society for Neuroscience}, abstract = {Exposure to uncontrollable stress [inescapable tailshock (IS)] produces behavioral changes that do not occur if the stressor is controllable [escapable tailshock (ES)] an outcome that is mediated by greater IS-induced dorsal raphe nucleus (DRN) serotonin [5-hydroxytryptamine (5-HT)] activation. It has been proposed that this differential activation occurs because the presence of control leads to top{\textendash}down inhibition of the DRN from medial prefrontal cortex (mPFC), not because uncontrollability produces greater excitatory input. Although mPFC inhibitory regulation over DRN 5-HT activation has received considerable attention, the relevant excitatory inputs that drive DRN 5-HT during stress have not. The lateral habenula (LHb) provides a major excitatory input to the DRN, but very little is known about the role of the LHb in regulating DRN-dependent behaviors. Here, optogenetic silencing of the LHb during IS blocked the typical anxiety-like behaviors produced by IS in male rats. Moreover, LHb silencing blocked the increase in extracellular basolateral amygdala 5-HT during IS and, surprisingly, during behavioral testing the following day. We also provide evidence that LHb{\textendash}DRN pathway activation is not sensitive to the dimension of behavioral control. Overall, these experiments highlight a critical role for LHb in driving DRN activation and 5-HT release into downstream circuits that mediate anxiety-like behavioral outcomes of IS and further support the idea that behavioral control does not modulate excitatory inputs to the DRN.}, URL = {https://www.eneuro.org/content/3/5/ENEURO.0229-16.2016}, eprint = {https://www.eneuro.org/content/3/5/ENEURO.0229-16.2016.full.pdf}, journal = {eNeuro} }