Academic Commons


Hyperfunction of Muscarinic Receptor Maintains Long-Term Memory in 5-HT4 Receptor Knock-Out Mice

Segu, Luis; Dumuis, Aline; Berrard, Sylvie; Bockaert, Joël; Buhot, Marie-Christine; Compan, Valérie; Hen, Rene; Lecomte, Marie-José; Wolff, Mathieu; Santamaria, Julie

Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR4), but whether an absence of these receptors modifies learning and memory is unexplored. In the spatial version of the Morris water maze, we show that 5-HTR4 knock-out (KO) and wild-type (WT) mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR4 control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR4. Inactivating muscarinic receptor with scopolamine, at an ineffective dose (0.8 mg/kg) to alter memory in WT mice, decreased long-term but not short-term memory of 5-HTR4 KO mice. Other changes included decreases in the activity of choline acetyltransferase (ChAT), the required enzyme for acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR4 KO under baseline conditions. Training- and scopolamine-induced increase and decrease, respectively in ChAT activity in the septum in WT mice were not detected in the 5-HTR4 KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR4 to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR4 aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR4 mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.


Also Published In

More About This Work

Academic Units
Public Library of Science
Published Here
March 8, 2016
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.