AbstractThe thalamus plays a central role in sensory information processing and regulation of innate behaviors such as feeding and sleep. Recent studies have revealed substantial evolutionary divergence in the inhibitory neuronal composition of the thalamus between primates and rodents. In this study, we identified a novel population of primate-specific thalamic inhibitory neurons (Th-INs) characterized by high expression of GAD1 and GAD2 but low expression of conventional markers (PV, SST, NPY, CCK). These Th-INs exhibit unique gene expression patterns, including PCBP3 and CHRM2, and were localized specifically to the thalamus in marmosets via RNA-FISH.To investigate their function, we performed enhancer screening using AAV vectors carrying candidate sequences and barcoded reporters. One enhancer (E5) showed high specificity (>90%) for Th-INs in marmosets, but failed to induce expression in mouse brains, supporting its primate specificity. Using this enhancer, we conducted circuit tracing and behavioral experiments. Tracing revealed that Th-INs receive inputs from both intra-thalamic excitatory neurons and cortical areas including the prefrontal, somatosensory, and auditory cortices. Behaviorally, chemogenetic manipulation of Th-INs significantly altered task performance in marmosets, including motivation (progressive ratio), working memory, and set-shifting tasks.Finally, we applied Prime editing and systemic AAV delivery to generate schizophrenia model marmosets with mutations in high-risk loci. Chemogenetic activation of Th-INs showed promising therapeutic effects, suggesting their potential as targets in psychiatric disorders. This study provides new insights into the evolutionary significance and functional roles of primate-specific inhibitory circuits in the thalamus.はじめに視床は，摂食や睡眠等の本能行動，また感覚器から大脳皮質への入力を介在・調整する重要な脳幹領域である．近年，霊長類と齧歯類には視床の神経細胞構成に大きな進化的種差があることが示され，具体的には抑制性神経細胞の割合・分布の大きな差が明らかにされてきた．本研究においては，霊長類において視床の高次的な機能を支える特異的な細胞構成に焦点を当て，これまで齧歯類モデルでは慶應義塾大学医学部生理学教室・訪問研究員吉松 祥― 281 ―霊長類脳における神経老化制御メカニズムの解明Elucidation of neural aging mechanism in primate brain
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