Linking serotonergic median raphe input to dorsal CA1 with mnemonic functions

Abstract

The role of serotonergic signaling within the hippocampus and its role in mnemonic function is still not well understood. We used optogenetics to specifically alter median raphe serotonin input to the dorsal CA1 subfield to investigate its role in hippocampus-dependent behavior. Unexpectedly, neither activation nor inhibition of serotonin release at dCA1 fiber terminals significantly modulated object recognition, spatial memory, or anxiety behavior. Nevertehless, we observed opposite effects of increased and decreased serotonergic input on spatial learning, and a marked reduction in the use of a direct search strategy in spatial navigation following activation of serotonergic terminals in dCA1, i.e. release of serotonin.Furthermore, since the 5-HT1A receptor is one of the most abundant serotonergic receptors in CA1, we also optogenetically activated 5-HT1A pathways specifically in pyrdamidal neurons of dCA1. Activation of 5-HT1A signaling significantly improved spatial memory without affecting object recognition or avoidance behavior. In conclusion, our data reveal modulatory effects of serotonin specifically on the acquisition of spatial memory.