Serotonin-mediated inhibition of ventral hippocampus is required for sustained goal-directed behavior

The ability to sustain goal-directed action is essential for success in many domains, but little is known about the corresponding neural substrates. Using fiber photometry to monitor population neural activity, we demonstrate that engagement in sustained food- or punishment-motivated behavior is associated with suppression of ventral but not dorsal hippocampal activity. Using optogenetic stimulation, we demonstrate that this suppression is required for goal-directed behavior, whereas optogenetic suppression of the ventral hippocampus (vHP) enhances the ability to sustain goal-directed behavior. Suppression of vHP during sustained goal-directed behavior was accompanied by increased activity in median but not dorsal raphe, implicating serotonergic signaling through Htr3a as a mechanism of vHP suppression during successful goal-directed behavior. Sustainment of goal-directed action may require suppression of vHP because of the structure’s well-documented role in behavioral inhibition. Yoshida et al. show in mice that sustained engagement in motivated behavior requires suppression of ventral hippocampus activity through activation of median raphe serotonin neurons.