Author:
Sanberg Cyndy Davis,Jones Floretta L.,Do Viet H.,Dieguez Dario,Derrick Brian E.
Abstract
Numerous studies suggest roles for monoamines in modulating long-term
potentiation (LTP). Previously, we reported that both induction and
maintenance of perforant path-dentate gyrus LTP is enhanced when induced while
animals explore novel environments. Here we investigate the contribution of
serotonin and 5-HT1a receptors to the novelty-mediated enhancement of LTP. In
freely moving animals, systemic administration of the selective 5-HT1a
antagonist WAY-100635 (WAY) attenuated LTP in a dose-dependent manner when LTP
was induced while animals explored novel cages. In contrast, LTP was
completely unaffected by WAY when induced in familiar environments. LTP was
also blocked in anesthetized animals by direct application of WAY to the
dentate gyrus, but not to the median raphe nucleus (MRN), suggesting the
effect of systemic WAY is mediated by a block of dentate 5-HT1a receptors.
Paradoxically, systemic administration of the 5-HT1a agonist 8-OH-DPAT also
attenuated LTP. This attenuation was mimicked in anesthetized animals
following application of 8-OH-DPAT to the MRN, but not the dentate gyrus. In
addition, application of a 5-HT1a agonist to the dentate gyrus reduced somatic
GABAergic inhibition. Because serotonergic projections from the MRN terminate
on dentate inhibitory interneurons, these data suggest 5-HT1a receptors
contribute to LTP induction via inhibition of GABAergic interneurons.
Moreover, activation of raphe 5-HT1a autoreceptors, which inhibits serotonin
release, attenuated LTP induction even in familiar environments. This suggests
that serotonin normally contributes to dentate LTP induction in a variety of
behavioral states. Together, these data suggest that serotonin and dentate
5-HT1a receptors play a permissive role in dentate LTP induction, particularly
in novel conditions, and presumably, during the encoding of novel,
hippocampus-relevant information.
Publisher
Cold Spring Harbor Laboratory
Subject
Cellular and Molecular Neuroscience,Cognitive Neuroscience,Neuropsychology and Physiological Psychology
Cited by
31 articles.
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