Abstract
Serotonin receptor 1A knockout (Htr1aKO) mice show increased anxiety-related behavior in tests measuring innate avoidance. Here we demonstrate that Htr1aKO 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 Htr1aKO 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.
| Original language | English |
|---|---|
| Pages (from-to) | 896-902 |
| Number of pages | 7 |
| Journal | Nature Neuroscience |
| Volume | 10 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 8 2007 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Suppression of conditioning to ambiguous cues by pharmacogenetic inhibition of the dentate gyrus. / Tsetsenis, Theodoros; Ma, Xiao Hong; Lo Iacono, Luisa; Beck, Sheryl G.; Gross, Cornelius.
In: Nature Neuroscience, Vol. 10, No. 7, 08.07.2007, p. 896-902.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Suppression of conditioning to ambiguous cues by pharmacogenetic inhibition of the dentate gyrus
AU - Tsetsenis, Theodoros
AU - Ma, Xiao Hong
AU - Lo Iacono, Luisa
AU - Beck, Sheryl G.
AU - Gross, Cornelius
PY - 2007/7/8
Y1 - 2007/7/8
N2 - Serotonin receptor 1A knockout (Htr1aKO) mice show increased anxiety-related behavior in tests measuring innate avoidance. Here we demonstrate that Htr1aKO 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 Htr1aKO 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.
AB - Serotonin receptor 1A knockout (Htr1aKO) mice show increased anxiety-related behavior in tests measuring innate avoidance. Here we demonstrate that Htr1aKO 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 Htr1aKO 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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U2 - 10.1038/nn1919
DO - 10.1038/nn1919
M3 - Article
C2 - 17558402
AN - SCOPUS:34347363003
VL - 10
SP - 896
EP - 902
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 7
ER -