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

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

Title:
Hyperfunction of Muscarinic Receptor Maintains Long-Term Memory in 5-HT4 Receptor Knock-Out Mice
Author(s):
Segu, Luis
Dumuis, Aline
Berrard, Sylvie
Bockaert, Joël
Buhot, Marie-Christine
Compan, Valérie
Hen, Rene
Lecomte, Marie-José
Wolff, Mathieu
Santamaria, Julie
Date:
Type:
Articles
Department(s):
Psychiatry
Volume:
5
Persistent URL:
Book/Journal Title:
PLoS ONE
Publisher:
Public Library of Science
Abstract:
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.
Subject(s):
Muscarinic receptors
Serotonin--Receptors
Hippocampus (Brain)
Long-term memory
Molecular biology
Medical sciences
Neurosciences
Publisher DOI:
https://doi.org/10.1371/journal.pone.0009529
Item views
85
Metadata:
text | xml
Suggested Citation:
Luis Segu, Aline Dumuis, Sylvie Berrard, Joël Bockaert, Marie-Christine Buhot, Valérie Compan, Rene Hen, Marie-José Lecomte, Mathieu Wolff, Julie Santamaria, , Hyperfunction of Muscarinic Receptor Maintains Long-Term Memory in 5-HT4 Receptor Knock-Out Mice, Columbia University Academic Commons, .

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