Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor knock-out mice.
Patients suffering from dementia of Alzheimer's type express less serotonin 4 receptors (5-HTR(4)), 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-HTR(4) knock-out (KO) and wild-type (WT) mice performed similarly for spatial learning, short- and long-term retention. Since 5-HTR(4) control mnesic abilities, we tested whether cholinergic system had circumvented the absence of 5-HTR(4). 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-HTR(4) 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-HTR(4) 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-HTR(4) KO animals. Findings suggest that adaptive changes in cholinergic systems may circumvent the absence of 5-HTR(4) to maintain long-term memory under baseline conditions. In contrast, despite adaptive mechanisms, the absence of 5-HTR(4) aggravates scopolamine-induced memory impairments. The mechanisms whereby 5-HTR(4) mediate a tonic influence on ChAT activity and muscarinic receptors remain to be determined.
Segu
Luis
L
Centre de Neurosciences Intégratives et Cognitives, CNRS UMR5228, Bordeaux University, Talence, France.
Lecomte
Marie-José
MJ
Wolff
Mathieu
M
Santamaria
Julie
J
Hen
René
R
Dumuis
Aline
A
Berrard
Sylvie
S
Bockaert
Joël
J
Buhot
Marie-Christine
MC
Compan
Valérie
V
D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D008124:Locomotion; D008297:Male; D018782:Maze Learning; D008568:Memory; D057567:Memory, Long-Term; D008570:Memory, Short-Term; D051379:Mice; D018345:Mice, Knockout; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics* / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D044422:Receptors, Serotonin, 5-HT4; D012601:Scopolamine