RT Journal Article SR Electronic T1 Two Functionally Distinct Serotonergic Projections into Hippocampus JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4936 OP 4944 DO 10.1523/JNEUROSCI.2724-19.2020 VO 40 IS 25 A1 Luchetti, Alessandro A1 Bota, Ayaka A1 Weitemier, Adam A1 Mizuta, Kotaro A1 Sato, Masaaki A1 Islam, Tanvir A1 McHugh, Thomas J. A1 Tashiro, Ayumu A1 Hayashi, Yasunori YR 2020 UL http://www.jneurosci.org/content/40/25/4936.abstract AB Hippocampus receives dense serotonergic input specifically from raphe nuclei. However, what information is carried by this input and its impact on behavior has not been fully elucidated. Here we used in vivo two-photon imaging of activity of hippocampal median raphe projection fibers in behaving male and female mice and identified two distinct populations: one linked to reward delivery and the other to locomotion. Local optogenetic manipulation of these fibers confirmed a functional role for these projections in the modulation of reward-induced behavior. The diverse function of serotonergic inputs suggests a key role in integrating locomotion and reward information into the hippocampal CA1.SIGNIFICANCE STATEMENT Information constantly flows in the hippocampus, but only some of it is captured as a memory. One potential process that discriminates which information should be remembered is concomitance with reward. In this work, we report a neuromodulatory pathway, which delivers reward signal as well as locomotion signal to the hippocampal CA1. We found that the serotonergic system delivers heterogeneous input that may be integrated by the hippocampus to support its mnemonic functions. It is dynamically involved in regulating behavior through interaction with the hippocampus. Our results suggest that the serotonergic system interacts with the hippocampus in a dynamic and behaviorally specific manner to regulate reward-related information processing.