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Functional roles of neural circuits linking monkey prefrontal cortex and mediodorsal thalamus in cognitive flexibility

https://repo.qst.go.jp/records/2002758
https://repo.qst.go.jp/records/2002758
9365e32d-9832-4aa2-933b-235caaa640ec
アイテムタイプ 会議発表用資料 / Presentation(1)
公開日 2026-02-12
タイトル
タイトル Functional roles of neural circuits linking monkey prefrontal cortex and mediodorsal thalamus in cognitive flexibility
言語 en
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言語 eng
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資源タイプ識別子 http://purl.org/coar/resource_type/c_6670
資源タイプ conference poster
著者 Oyama Kei

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Oyama Kei

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内容記述 Animals must flexibly adapt to novel environments and optimize their behavior in a dynamically changing world. The prefrontal cortex (PFC) and the mediodorsal thalamus (MD) are known to support such adaptive behavior through their reciprocal connectivity and via the PFC–basal ganglia–thalamus–PFC loop. However, the specific contribution of these circuits to cognitive flexibility in primates remains unclear. To address this, we performed large-scale neuronal recordings using Neuropixels probes in a macaque monkey engaged in a modified version of the Wisconsin Card Sorting Test (WCST). Recordings targeted the dorsolateral PFC (dlPFC), along with two of its major projection sites: the parvocellular nucleus of the mediodorsal thalamus (MDpc) and the dorsal part of the caudate head (dCDh). In the WCST, the monkey was required to adapt to flexible switch between rules (based on the color or shape of a sample stimulus) and maintain the current rule to categorize subsequent stimuli, providing a robust measure of behavioral flexibility. We found that neuronal populations across all three regions encoded various task-related information, including the current rule, with particularly strong rule representation observed in MD neurons. To examine the causal roles, we employed multiplexed chemogenetic manipulations. Inhibitory Designer Receptors Exclusively Activated by Designer Drugs (hM4Di) and Pharmacologically Selective Actuator Modules (PSAM4-GlyR) were virally expressed in the dlPFC and MDpc, and neuronal activity was reversibly silenced via systemic administration of their respective agonists, deschloroclozapine and uPSEM817. Silencing the dlPFC significantly impaired WCST performance immediately after rule switches—when adaptation to a new rule was required—and concurrently reduced rule-related signals in MDpc neurons, but not in dCDh neurons. In contrast, silencing the MDpc impaired performance during rule maintenance (i.e., after successful rule acquisition), without affecting rule representations in either the dCDh or the dlPFC. These findings demonstrate distinct yet complementary roles of the dlPFC and MDpc in supporting rule-based flexible behavior. Especially, they underscore the importance of direct dlPFC-MD projections as a key neural substrate for cognitive flexibility in primates.
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内容記述 Neuroscience2025
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日付 2025-11-16
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