The Serotoninergic system mediates interference resolution during memory retrieval phase in mice

MORICI JUAN FACUNDO; GALLO FRANCISCO; MIRANDA MAGDALENA; ZANONI BELEN; BEKINSCHTEIN PEDRO; NOELIA WEISSTAUB

Congreso; Congreso de la SAN 2016; 2015

Serotonin (5-HT) plays a role in the control of impulsive an other types ofbehavior. Increasing evidence shows that 5-HT is involved in learning andmemory processes. However, role of 5-HT in recognition memory ispoorly understood in particular in conditions that cause interference betweenmemory traces. We have shown that blocking 5-HT2AR or activating5-HT1AR in the medial prefrontal cortex (mPFC) of rats impairs the resolutionof an object in context task (OIC) in which the animal has to recognizea novel combination of a familiar object and a familiar context. Wepostulated that both receptors might play a role in the resolution of OIC.If this is the case, then an imbalance of 5-HT2AR or 5-HT1AR signalingmight alter the mnemonic function of mPFC. We tested this hypothesisusing a genetically modied mice that present a global disruption of5-HT2AR (htr2a-/-). We exposed htr2a -/- and htr2a+/+ to the OIC task. Wefound that htr2a -/- mice showed a decit in the resolution of the OIC tasksimilar to the one observed in rats when 5-HT2AR was blocked in mPFCduring memory retrieval. Infusion of a selective 5-HT1AR antagonist inthe mPFC before the retrieval session rescued the discrimination decitobserved in htr2a-/- mice without aecting the performance in htr2a+/+mice. These result suggest that 5-HT modulates mPFC function through5-HT1AR and 5-HT2AR and that in the absence of 5-HT2AR, 5-HT1A signalingaects the ability of the mPFC to control memory interference.