Nogo-A-mediated constraints on activity-dependent synaptic plasticity and associativity in rat hippocampal CA2 synapses

IF 2.4 3区 医学 Q3 NEUROSCIENCES
Hippocampus Pub Date : 2024-08-02 DOI:10.1002/hipo.23625
Maria Vazquez Pavon, Sheeja Navakkode, Sreedharan Sajikumar
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Abstract

Hippocampal area CA2 has garnered attention in recent times owing to its significant involvement in social memory and distinctive plasticity characteristics. Research has revealed that the CA2 region demonstrates a remarkable resistance to plasticity, particularly in the Schaffer Collateral (SC)-CA2 pathway. In this study we investigated the role of Nogo-A, a well-known axon growth inhibitor and more recently discovered plasticity regulator, in modulating plasticity within the CA2 region. The findings demonstrate that blocking Nogo-A in male rat hippocampal slices facilitates the establishment of both short-term and long-term plasticity in the SC-CA2 pathway, while having no impact on the Entorhinal Cortical (EC)-CA2 pathway. Additionally, the study reveals that inhibiting Nogo-A enables association between the SC and EC pathways. Mechanistically, we confirm that Nogo-A operates through its well-known co-receptor, p75 neurotrophin receptor (p75NTR), and its downstream signaling factor such as Rho-associated protein kinase (ROCK), as their inhibition also allows plasticity induction in the SC-CA2 pathway. Additionally, the induction of long-term depression (LTD) in both the EC and SC-CA2 pathways led to persistent LTD, which was not affected by Nogo-A inhibition. Our study demonstrates the involvement of Nogo-A mediated signaling mechanisms in limiting synaptic plasticity within the CA2 region.

Abstract Image

Nogo-A介导的对大鼠海马CA2突触的活动依赖性突触可塑性和联想性的制约。
海马 CA2 区因其在社会记忆中的重要作用和独特的可塑性特征而在近期备受关注。研究发现,CA2 区对可塑性具有显著的抵抗力,尤其是在沙弗侧(SC)-CA2 通路上。在这项研究中,我们调查了 Nogo-A 在调节 CA2 区可塑性中的作用,Nogo-A 是一种著名的轴突生长抑制剂,也是最近发现的可塑性调节剂。研究结果表明,在雄性大鼠海马切片中阻断Nogo-A可促进SC-CA2通路中短期和长期可塑性的建立,同时对内皮质(EC)-CA2通路没有影响。此外,该研究还发现,抑制 Nogo-A 可使 SC 和 EC 通路之间产生联系。从机理上讲,我们证实了Nogo-A是通过其著名的共受体p75神经营养素受体(p75NTR)及其下游信号因子如Rho相关蛋白激酶(ROCK)发挥作用的,因为抑制它们也能诱导SC-CA2通路的可塑性。此外,在EC和SC-CA2通路中诱导长期抑制(LTD)会导致持续的LTD,而Nogo-A抑制不会影响这种LTD。我们的研究表明,Nogo-A介导的信号机制参与限制了CA2区域的突触可塑性。
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来源期刊
Hippocampus
Hippocampus 医学-神经科学
CiteScore
5.80
自引率
5.70%
发文量
79
审稿时长
3-8 weeks
期刊介绍: Hippocampus provides a forum for the exchange of current information between investigators interested in the neurobiology of the hippocampal formation and related structures. While the relationships of submitted papers to the hippocampal formation will be evaluated liberally, the substance of appropriate papers should deal with the hippocampal formation per se or with the interaction between the hippocampal formation and other brain regions. The scope of Hippocampus is wide: single and multidisciplinary experimental studies from all fields of basic science, theoretical papers, papers dealing with hippocampal preparations as models for understanding the central nervous system, and clinical studies will be considered for publication. The Editor especially encourages the submission of papers that contribute to a functional understanding of the hippocampal formation.
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