| 研究実績の概要 |
I have mapped the anatomical pathways from PAG to midline/intralaminar thalamus, and identified several nuclei which receive PAG inputs and send projections to the LA/B. Our study (recently published on Nature Neuroscience) has shown that distinct PAG sub-regions (dorsolateral and ventrolateral PAG) regulate multiple facets of instructive signals during fear conditioning. Therefore, I emphasized differential anatomical connectivity between PAG subdivisions and the midline/intralaminar thalamus. I performed retrograde, trans-synaptic viral tracing with Rabies-virus-based tools. Dorsolateral PAG neurons preferentially target anterior paraventricular nucleus of thalamus (aPVT) and anterior central medial thalamus (aCM). In contrast, ventrolareral PAG neurons project strongly to the posterior PVT (pPVT) and posterior CM (pCM). Those thalamus-projecting PAG neurons are mostly glutamatergic. As the subdivisions of PAG mediate distinct fear learning processes, the topography of PAG outputs to thalamic nuclei may be important for directing diverse aversive signals.
Next, I confirmed the dorsolateral PAG and midline/intralaminar thalamus engaged in processing of aversive unconditional stimuli (US). The expression of immediate early gene c-fos is widely used as a neuronal activity marker. After receiving immediate footshocks, the number of c-fos immunoreactive cells significantly increased in dorsolateral PAG, PVT and CM. The footshock-induced c-fos expression supports the hypothesis that PAG and midline/ intralaminar thalamus neurons are involved in aversive signaling.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
The thorough anatomical tracing from PAG to intra-laminar thalamus was completed, which is consistent with the 年次計画 in my proposal. In addition, the pain stimuli robustly induced the expression of immediate-early genes in PAG, intra-laminar thalamus and LA/B. This indicates the neuronal activities in these regions correlate with aversive information processing. In sum, the anatomical and functional findings are in agreement with my hypothesis.
Current findings suggest that the PAG and midline/intralaminar thalamus are parts of aversive signaling pathways which may instruct the fear memory formation. These works set stage for upcoming optogenetic experiments, which will examine the functional contribution of these neural circuits to fear learning.
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| 今後の研究の推進方策 |
Recently, I have applied the optogenetic tools to PAG-thalamus circuits. The expressions of opsins in these brain regions are verified. Now the optogenetic manipulations on freely moving rats are ongoing, and their impacts on fear learning are now evaluated. The electrophysiological recording will follow, after the behavioral effects are confirmed.
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