Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Hạch hạnh nhân điều chỉnh sự ức chế trước xung của phản xạ giật mình thính giác thông qua các đầu vào kích thích đến nhân tủy dọc phía sau
Tóm tắt
Sự ức chế cảm vận là một quá trình tiền chú ý cơ bản được định nghĩa là sự ức chế phản ứng vận động bởi một sự kiện cảm giác. Sự ức chế cảm vận, thường được đo lường thông qua ức chế trước xung (PPI) của phản xạ giật mình thính giác, bị suy giảm ở những bệnh nhân mắc các rối loạn thần kinh và tâm thần khác nhau. Sự thiếu hụt PPI là một dấu hiệu đặc trưng của tâm thần phân liệt, và thường liên quan đến sự chú ý và các suy giảm nhận thức khác. Mặc dù sự đảo ngược của sự thiếu hụt PPI trong các mô hình động vật thường được sử dụng trong nghiên cứu tiền lâm sàng để sàng lọc thuốc chống loạn thần, các hệ thống chất dẫn truyền thần kinh và cơ chế synap chịu trách nhiệm cho PPI vẫn chưa được làm sáng tỏ, ngay cả trong các điều kiện sinh lý. Bằng chứng gần đây đã bác bỏ giả thuyết lâu đời rằng PPI được trung gian hóa bởi các đầu vào cholinergic từ vùng giữa não đến nhân tủy dọc phía sau (PnC). Thay vào đó, các cơ chế ức chế glutamatergic, glycinergic và GABAergic hiện nay được cho là có vai trò quan trọng đối với PPI ở mức PnC. Vì rối loạn hạch hạnh nhân làm thay đổi PPI và là phổ biến trong các bệnh lý thể hiện sự thiếu hụt ức chế cảm vận, nghiên cứu hiện tại được thiết kế để kiểm tra rằng các sự chiếu trực tiếp tới PnC do hạch hạnh nhân tạo ra góp phần vào PPI. Sử dụng chuột loại hoang dã và chuột chuyển gen biểu hiện eGFP dưới sự điều khiển của trình điều khiển glycine transporter loại 2 (chuột GlyT2-eGFP), trước tiên chúng tôi đã áp dụng phương pháp theo dõi đường đi, tái tạo hình thái và phân tích hóa mô miễn dịch để chứng minh rằng nhân trung tâm của hạch hạnh nhân (CeA) gửi các đầu vào glutamatergic đến các nơ-ron PnC bên sau, bao gồm cả các tế bào GlyT2+. Sau đó, chúng tôi cho thấy sự đóng góp của các synapse kích thích CeA-PnC vào PPI in vivo bằng cách chứng minh rằng việc ức chế bằng quang học kết nối này làm giảm PPI, và kích thích bằng quang học gây ra PPI một phần. Cuối cùng, ở chuột GlyT2-Cre, việc ghi nhận toàn bộ tế bào của các nơ-ron GlyT2+ PnC in vitro kết hợp với kích thích bằng quang học các sợi CeA, cũng như việc ức chế ánh sáng các nơ-ron GlyT2+ PnC in vivo, đã cho phép chúng tôi gợi ý rằng các nơ-ron GlyT2+ tham gia vào con đường PPI. Kết quả của chúng tôi tiết lộ một cơ chế ức chế feedforward trong mạch khởi động của thân não mà qua đó các đầu vào glutamatergic từ hạch hạnh nhân và các nơ-ron GlyT2+ PnC góp phần vào PPI. Chúng tôi đang cung cấp những hiểu biết mới về cấu trúc lý thuyết có liên quan lâm sàng của PPI, mà bị rối loạn trong nhiều bệnh tâm thần và thần kinh khác nhau.
Từ khóa
#sự ức chế trước xung #phản xạ giật mình thính giác #hạch hạnh nhân #nhân tủy dọc phía sau #glycine transporter #tế bào GlyT2 #synapse kích thíchTài liệu tham khảo
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