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Summary: Major depressive disorder (MDD) is among the most common mental illnesses. Serotonergic (5-HT) neurons are central to the pathophysiology and treatment of MDD. Repeatedly recalling positive episodes is effective for MDD. Stimulating 5-HT neurons of the dorsal raphe nucleus (DRN) or neuronal ensembles in the dorsal dentate gyrus (dDG) associated with positive memories reverses the stress-induced behavioral abnormalities. Despite this phenotypic similarity, their causal relationship is unclear. This study revealed that the DRN 5-HT neurons activate dDG neurons; surprisingly, this activation was specifically observed in positive memory ensembles rather than neutral or negative ensembles. Furthermore, we revealed that dopaminergic signaling induced by activation of DRN 5-HT neurons projecting to the ventral tegmental area mediates an increase in active coping behavior and positive dDG ensemble reactivation. Our study identifies a role of DRN 5-HT neurons as specific reactivators of positive memories and provides insights into how serotonin elicits antidepressive effects.

Nicotine administration enhances object recognition memory. However, target brain regions and cellular mechanisms underlying the nicotine effects remain unclear. In mice, the novel object recognition test revealed that systemic nicotine administration before training enhanced object recognition memory. Moreover, this effect was inhibited by infusion of retigabine, a selective voltage-dependent potassium 7 (Kv7) channel opener, into the medial prefrontal cortex (mPFC) before nicotine administration. Additionally, infusion of XE-991, a selective Kv7 channel blocker, into the mPFC before training enhanced object recognition memory. Therefore, Kv7 channels in the mPFC may be at least partly involved in nicotine-induced enhancement of object recognition memory.

High impulsivity will increase the risk of criminal behavior, drug abuse, and suicide. We chose two drugs by following a strategy recently we proposed for identifying potential anti-impulsivity drugs, and examined the effects on impulsive action in rats by using a 3-choice serial reaction time task. We showed that the administration of blonanserin, an atypical antipsychotic, reduced impulsive actions in a U-shaped manner. 1-(2-Pyriidinyl)-piperazine, an active metabolite of buspirone or tandospirone, also slightly reduced impulsive actions, though it impaired motor functions. These results affirm the validity of our strategy, but require its refinement for developing anti-impulsivity drugs. Keywords: Impulsive behavior, 1-PP, Antipsychotics