Spatiotemporally Distinct Dopamine Domains in the Hippocampus

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 spatiotemporal 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.