Hippocampal proBDNF facilitates place learning strategy associated with neural activity in rats
Hippocampal proBDNF facilitates place learning strategy associated with neural activity in rats
复制标题
海马 proBDNF 促进大鼠神经活动相关的位置学习策略
DOI：
10.1007/s00429-018-1742-x
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发表时间：
2018-12-01
影响因子：
3.1
通讯作者：
Sun, Wei
中科院分区：
文献类型：
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作者：
An, Lei;Li, Xiaoliang;Sun, Wei
成熟的脑源性神经营养因子对突触可塑性和空间记忆有促进作用。BDNF的前体（proBDNF）已经作为针对其成熟形式的蛋白质出现。然而，目前尚不清楚proBDNF是否以及如何调节神经兴奋性和空间行为。通过向HPC中注入抗切割的proBDNF或其抗体，我们通过多种行为测试和记录海马单单位活动来寻找影响的证据。我们的行为学研究结果表明，proBDNF通过促进位置策略的使用和抑制反应策略，对空间学习产生了有益的影响，包括（1）使用更多的位置搜索策略，但减少反应策略，（2）增加大鼠选择位置策略的数量，但不选择反应策略。有趣的是，抗proBDNF抗体的输注并没有影响大鼠的训练过程，但使适应学习逆转训练更加困难，这表明在选择适当的学习策略方面存在缺陷。训练诱导的proBDNF的增加促进锥体神经元的放电率，但不是快速尖峰（FS）中间神经元。重要的是，内源性proBDNF促进了空间学习行为的神经相关性，而不是反应学习行为。然而，抗proBDNF抗体有效地逆转了策略偏好并抑制了神经活动。我们在此提出，proBDNF发挥关键作用的神经兴奋性和使用的认知策略，以促进空间学习过程。
Mature brain-derived neurotrophic factor has been shown to have a promotive effect on synaptic plasticity and spatial memory. The precursor of BDNF (proBDNF) has emerged as a protein against its mature form. However, it is unknown whether and how proBDNF regulates neural excitability and spatial behavior. Through infusion of cleavage-resistant proBDNF or its antibody into HPC, we sought evidence for the influences by employing multiple behavioral tests and recording hippocampal single-unit activity. Our behavioral findings showed that proBDNF induced beneficial effects on spatial learning by facilitating the use of the place strategy and inhibiting the response strategy, including (1) using more place search strategies but less response strategies, and (2) increasing the number of rats in choosing place strategies but not response strategies. Intriguingly, infusion of an anti-proBDNF antibody did not affect rats' training process but rendered the adaption to learning reversal training more difficult, indicating deficits in choosing the proper learning strategy. The training-induced increase in proBDNF promoted the firing rate of pyramidal neurons but not fast-spiking (FS) interneurons. Importantly, endogenous proBDNF facilitated the neural correlate of spatial, but not response, learning behavior. However, the anti-proBDNF antibody effectively reversed the strategy preference and inhibited neural activity. We herein propose that proBDNF exerts pivotal effects on neural excitability and the use of cognitive strategies to facilitate the spatial learning process.