| 研究実績の概要 |
The project aims at understanding the aversive circuits which trigger fear learning. I hypothesized that aversive signals are transmitted through the midline and intralaminar thalamic nuclei. First, I mapped the input-output pathways of various midline thalamic nuclei. Several midline thalamic regions receive PAG inputs and send projection to the lateral and basal amygdala (LA/B). Dorsolateral PAG (dlPAG) neurons preferentially target anterior midline thalamus (aMT). In contrast, ventrolareral PAG (vlPAG) neurons project strongly to the posterior midline thalamus (pMT). Aversive stimuli, namely footshocks, evoke the immediate gene expression (c-fos) in LA/B projection neurons of the midline thalamus. These results suggest that the midline thalamus transmits aversive signal to LA/B. I then targeted the PAG-midline thalamus projections by expressing inhibitory opsin ArchT in PAG, and optogenetically disrupted aversive signaling during fear conditioning. Optogenetic inhibition of dlPAG-aMT neurons attenuated fear learning; however, inhibition of other PAG-thalamus circuits had no effect on learning. The results demonstrate an anatomical and functional segregation in PAG-thalamus circuits. That is, the aMT-projecting neurons in dlPAG are critical for conveying aversive signals during fear learning, while other nuclei in PAG and thalamus do not contribute directly to this process. In sum, the findings advance the understanding of circuit mechanisms of emotional learning and adaptive behaviors by showing how aversive information reaches the LA/B to induce fear learning.
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