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Publication : Suppression of conditioning to ambiguous cues by pharmacogenetic inhibition of the dentate gyrus.

First Author  Tsetsenis T Year  2007
Journal  Nat Neurosci Volume  10
Issue  7 Pages  896-902
PubMed ID  17558402 Mgi Jnum  J:124035
Mgi Id  MGI:3720421 Doi  10.1038/nn1919
Citation  Tsetsenis T, et al. (2007) Suppression of conditioning to ambiguous cues by pharmacogenetic inhibition of the dentate gyrus. Nat Neurosci 10(7):896-902
abstractText  Serotonin receptor 1A knockout (Htr1a(KO)) mice show increased anxiety-related behavior in tests measuring innate avoidance. Here we demonstrate that Htr1a(KO) mice show enhanced fear conditioning to ambiguous conditioned stimuli, a hallmark of human anxiety. To examine the involvement of specific forebrain circuits in this phenotype, we developed a pharmacogenetic technique for the rapid tissue- and cell type-specific silencing of neural activity in vivo. Inhibition of neurons in the central nucleus of the amygdala suppressed conditioned responses to both ambiguous and nonambiguous cues. In contrast, inhibition of hippocampal dentate gyrus granule cells selectively suppressed conditioned responses to ambiguous cues and reversed the knockout phenotype. These data demonstrate that Htr1a(KO) mice have a bias in the processing of threatening cues that is moderated by hippocampal mossy-fiber circuits, and suggest that the hippocampus is important in the response to ambiguous aversive stimuli.
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