講師資料
Talks：
Hypocretin in medial prefrontal cortex mediates fear extinction in PTSD
內側前額葉皮層中的下視丘泌素對創傷後壓力症候群中的恐懼消退之作用
Name：
張芳嘉（Fang-Chia Chang）
Position：
Distinguished Professor
Affiliation：
Department of Veterinary Medicine
Neurobiology and Cognitive Science Research Center
National Taiwan University
Email：
Photo：
Research Interests：
Neuroimmunomodulation in sleep-wake regulation, neurological diseases (Parkinson’s disease, Alzheimer’s disease, epilepsy, stress, and posttraumatic stress disorder (PTSD))-related sleep disruptions and their neural circuits, novel therapeutic approaches for epilepsy, PTSD, Alzheimer’s disease and insomnia, herbal drug development and acupuncture therapy.
Selected Publications：
1. Yun Lo, Pei-Lu Yi, Yi-Tse Hsiao, Tung-Yen Lee, Fang-Chia Chang*. A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity. Communications Biology 2023; 6:716; https://doi.org/10.1038/s42003-023-05090-9
2. Tung-Yen Lee, Pei-Lu Yi, Fang-Chia Chang*. Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice. Frontiers in Psychiatry 2023; 14:1196994; https://doi.org/10.3389/fpsyt.2023.1196994
3. Yun Lo, Pei-Lu Yi, Yi-Tse Hsiao, Fang-Chia Chang*. Hypocretin in locus coeruleus and dorsal raphe nucleus mediates inescapable footshock stimulation (IFS)-induced REM sleep alteration. Sleep 2022; 45(3): zsab301; https://doi.org/10.1093/sleep/zsab301
Abstract：
Introduction:
Post-traumatic stress disorder (PTSD) is characterized by impaired discrimination of trauma-associated fear memories, leading to persistent emotional distress and sleep disruption. The orexin system in the lateral hypothalamus (LH) has been implicated in the recall of extinguished fear memories, while lesions of the medial prefrontal cortex (mPFC)—a major downstream target of the LH—disrupt extinction processes. These findings suggest that orexinergic projections from the LH to the mPFC may contribute to both conditioned fear extinction and sleep regulation.
Methods:
Using chemogenetic approaches, we selectively activated or inhibited the LH–mPFC pathway during extinction learning. Electrocorticography was applied in parallel to assess sleep states under these manipulations.
Results:
Extinction acquisition was accompanied by heightened activity in both the LH and mPFC. Activation of the LH–mPFC pathway sustained elevated freezing behavior during extinction, whereas silencing this pathway produced an early reduction in freezing that declined rapidly. Pathway manipulation not only altered freezing behavior but also affected extinction memory formation, as confirmed by retrieval and anxiety-related behavioral tasks. Moreover, pathway activation induced insomnia-like phenotypes during the light period.
Conclusion:
These findings indicate that orexinergic projections from the LH to the mPFC play a critical role in the extinction of conditioned fear memories while concurrently modulating REM sleep regulation.
2025年會：