Optogenetic activation of dorsal raphe serotonin neurons induces a brain-wide response in reward network

Abstract Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects through its brain-wide projections and variety of receptors remains unclear. Here we measured the brain-wide response to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) by functional MRI using an 11.7T scanner with a cryoprobe. Transient activation of DRN serotonin neurons caused wide-spread activation of reward-related brain areas. The same stimulation under anesthesia with isoflurane decreased activation of those reward-related areas and the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 type receptors. The primarily facilitatory effect on reward-related brain areas by DRN serotonergic activation is consistent with recent discoveries of its roles in reward-oriented behaviors and demands reconsideration of inhibitory view due to the result under anesthesia.