[Tyra Talk] 2025-05-03 自閉症小鼠模型：PV中間神經元於前額葉發育早期的功能缺陷
本演講將帶大家了解，自閉症患者常見的大腦區域──內側前額葉皮質（mPFC）──在發育過程中是如何出現變化，進而影響認知與感官反應。匹茲堡大學博士生施議鈞（Yi-Chun Shih）利用一種帶有自閉症風險基因 SHANK3 缺失的小鼠，深入觀察兩類關鍵神經細胞的發育過程：興奮性的錐體細胞（pyramidal neurons, PYR）與抑制性的 parvalbumin 陽性中介神經元（parvalbumin-positive interneurons, PVIN）。研究發現，PVIN 在出生後早期表現出活性不足，導致大腦訊號的抑制功能受損，然而到了成年階段，PVIN 則轉為過度活躍，PYR 的興奮性則相對降低。這些結果顯示，成年動物中觀察到的異常表現，可能並非直接來自 SHANK3 基因缺陷，而是神經迴路在發育過程中為了補償早期 PVIN 功能失調所產生的自我適應結果。這項發現不僅揭示了神經發育中關鍵的時序變化，也指出了早期介入的潛在治療窗口。
|| 講者（Speaker）:
施議鈞 (Yi-Chun Shih)
I am a fifth-year grad student from center of neuroscience at University of Pittsburgh. My research focuses on studying neuronal and circuit deficits of corticostriatal circuit in Shank3B-KO mice, a well-studied mouse model for autism spectrum disorders (ASD), during early postnatal development by using electrophysiology and calcium imaging. I graduated from deparment of life science at National Taiwan University and got my master degree from the institute of molecular medicine. With solid training in Academia Sinica, I applied to grad school in the States to pursue my PhD in neuroscience. I joined Rui Peixoto's lab, who is an expert in cortico-corticostriatal deficit of ASD. Our lab study the development of corticostriatal circuits with ASD mouse models in early postnatal age (P7-P21) corresponding to the onset of ASD in human.
|| 摘要（Abstract）:
Medial prefrontal cortex (mPFC) dysfunction is associated with cognitive and sensory abnormalities in individuals with autism spectrum disorder (ASD), yet the trajectory of mPFC circuit development in these conditions remains poorly understood. In this study, we investigated the postnatal maturation of glutamatergic connectivity and neuronal excitability in pyramidal neurons (PYR) and parvalbumin-positive interneurons (PVIN) in the mPFC of mice harboring deletions in SHANK3, a well-established genetic cause of autism associated with severe cognitive impairments and seizures. Our findings reveal early deficits in PVIN excitability that precede changes in the synaptic and intrinsic properties of PYR, resulting in impaired feedforward inhibition. In vivo calcium imaging demonstrated hypoactivity of PVIN in dorsal mPFC circuits during early postnatal development, characterized by reduced calcium transients in PVIN. By adulthood, these excitability phenotypes were reversed, with PVIN becoming hyperexcitable and PYR hypoexcitable. These results suggest that early PVIN dysfunction in Shank3B-/- mice emerges during postnatal development and may represent a key pathogenic mechanism and potential therapeutic target in SHANK3-related disorders.
|| 研究領域（Field）:
自然科學、數學及統計領域
|| 研究子領域（Sub-field）:
神經生物學
|| 主持人（Chair）:
|| 活動時間（Event Time）:
05/03/2025 05:30 AM PDT Pacific Time
05/03/2025 06:30 AM MDT Mountain Time
05/03/2025 07:30 AM CDT Central Time
05/03/2025 08:30 AM EDT Eastern Time
05/03/2025 01:30 PM BST England
05/03/2025 02:30 PM CEST Berlin
05/03/2025 08:30 PM Taiwan
|| 圖像設計（Design）:
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