抄録
People who suffer from anxiety tend to interpret ambiguous situations, situations that could potentially be dangerous but not necessarily so, as threatening. It is also recognized that a person's propensity for anxiety can be influenced by early life experiences. We have shown that signaling by the neurotransmitter serotonin during early postnatal development in the mouse is about to moderate life-long anxiety behavior. Specifically, genetic or pharmacological blockade of the serotonin 1A receptor (Htr1aKO) during this period leads to increased anxiety both to innate anxiety cues (exposure novel arena) as well as enhanced fear conditioning to ambiguous, but not non-ambiguous conditioned stimuli. 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 non-ambiguous cues. In contrast, inhibition of hippocampal dentate gyrus granule cells selectively suppressed conditioned responses to ambiguous cues and reversed the Htr1aKO 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 plays an important role in the response to ambiguous aversive stimuli. [J Physiol Sci. 2008;58 Suppl:S2]
