The neuromodulator dopamine plays a critical role in orchestrating behavior by signaling actions and rewards. Dopamine signaling in the hippocampus is necessary for the formation of long-term memories but the functional correlates, anatomical organization, and spatio-temporal scale of hippocampal dopamine release remain largely unknown. Using high resolution, two-photon imaging of optical sensors in the hippocampus of male and female mice, we identified dopamine release in two closely apposed spatial domains. In Pavlovian conditioning, there was no significant dopamine release in early training but over days to weeks of experience, dopamine transients appeared at rewards in the "deep" domain of CA1 (basal dendritic layer). Surprisingly these transients did not strongly encode reward. The act of stopping and licking, used to collect reward, was sufficient to produce deep dopamine transients even without the conditioned stimulus or reward. Similarly, hippocampal dopamine transients showed no reward prediction error at surprise rewards. In a spatial goal-directed task, deep dopamine domain transients at rewards persisted but dopamine ramps now appeared, ramping up in the superficial domain (cell body and apical dendrites) during reward approach while ramping down in the deep domain. Our results reveal anatomically segregated hippocampal dopamine release domains with dynamic signaling that is distinct from striatal dopamine. Rather than a unitary volume and function of dopamine, we identify multiple spatial domains and functional signals that likely play distinct and dissociable roles in hippocampal-dependent learning and memory. Significance statement The hippocampus is necessary for forming long-term memories and the neuromodulator dopamine is critical in this process. Exactly how dopamine acts in the hippocampus remains opaque since there is no clear picture of when and where dopamine is released. Using newly developed optical dopamine sensors, we find that hippocampal dopamine release is split into two distinct spatial domains. In Pavlovian conditioning, the "deep" domain shows dopamine transients that largely correspond to actions used to consume rewards, while in a goal directed task, dopamine ramping appears in both domains during reward approach. Notably, distinct domains were initially absent and developed over experience. Our results reveal specific dopamine dynamics that are likely to play distinct and dissociable roles during behavior.
Molina et al. (Thu,) studied this question.