State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, China.
School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Beijing Laboratory of Oral Health, Capital Medical University, Beijing, 100069, China.
Neurosci Bull. 2024 Jun;40(6):732-742. doi: 10.1007/s12264-023-01163-1. Epub 2023 Dec 19.
The hippocampus is essential for learning and memory, but it also plays an important role in regulating emotional behavior, as hippocampal excitability and plasticity affect anxiety and fear. Brain synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1 (TIMP1), a known protein inhibitor of extracellular matrix (ECM), and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various stimuli. However, the involvement of Timp1 in fear learning, anxiety, and hippocampal synaptic function remains to be established. Our study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear learning. Electrophysiological results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region, but the basic synaptic transmission and plasticity were normal in the Schaffer collateral pathway. Taken together, our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors, but that Timp1 is not crucial for fear learning.
海马体对于学习和记忆至关重要，但它在调节情绪行为方面也起着重要作用，因为海马体的兴奋性和可塑性会影响焦虑和恐惧。脑突触可塑性可能受到基质金属蛋白酶组织抑制剂 1（TIMP1）的调节，TIMP1 是一种已知的细胞外基质（ECM）蛋白抑制剂，而神经元兴奋和各种刺激可以诱导海马体中 TIMP1 的表达。然而，Timp1 在恐惧学习、焦虑和海马体突触功能中的作用仍有待确定。我们在体内研究了 TIMP1 的功能，结果表明 TIMP1 基因敲除小鼠表现出焦虑样行为，但恐惧学习正常。电生理结果表明，Timp1 基因敲除小鼠在腹侧 CA1 区表现出过度活跃，但在 Schaffer 侧支通路上基本的突触传递和可塑性正常。综上所述，我们的研究结果表明，Timp1 在体内的缺失会导致焦虑行为的发生，但 Timp1 对于恐惧学习并不是至关重要的。
