Perturbed dentate gyrus function in serotonin 5-HT2C receptor mutant mice

AUTOR(ES)

Tecott, Laurence H.

FONTE

The National Academy of Sciences

RESUMO

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.

Documentos Relacionados

• Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase
• Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice
• Chinese hamster serotonin (5-HT) type 2 receptor cDNA sequence.
• Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene
• No hypothermic response to serotonin in 5-HT7 receptor knockout mice