Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice.
Serotonin systems have been implicated in the regulation of hippocampal function. Serotonin 5-HT2C receptors are widely expressed throughout the hippocampal formation, and these receptors have been proposed to modulate synaptic plasticity in the visual cortex. To assess the contribution of 5-HT2C receptors to the serotonergic regulation of hippocampal function, mice with a targeted 5-HT2C-receptor gene mutation were examined. An examination of long-term potentiation at each of four principal regions of the hippocampal formation revealed a selective impairment restricted to medial perforant path-dentate gyrus synapses of mutant mice. This deficit was accompanied by abnormal performance in behavioral assays associated with dentate gyrus function. 5-HT2C receptor mutants exhibited abnormal performance in the Morris water maze assay of spatial learning and reduced aversion to a novel environment. These deficits were selective and were not associated with a generalized learning deficit or with an impairment in the discrimination of spatial context. These results indicate that a genetic perturbation of serotonin receptor function can modulate dentate gyrus plasticity and that plasticity in this structure may contribute to neural mechanisms underlying hippocampus-dependent behaviors.
Tecott
L H
LH
Department of Psychiatry and Center for Neurobiology and Psychiatry, University of California, San Francisco, CA 94143-0984, USA. tecott@itsa.ucsf.edu
Logue
S F
SF
Wehner
J M
JM
Kauer
J A
JA
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D009154:Mutation; D011985:Receptors, Serotonin / Q000502:physiology*
D011985:Receptors, Serotonin