Mismatch novelty exploration training shifts VPAC1 receptor-mediated modulation of hippocampal synaptic plasticity by endogenous VIP in male rats

IF 2.9 3区医学 Q2 NEUROSCIENCES

Journal of Neuroscience Research Pub Date : 2024-04-24 DOI:10.1002/jnr.25333

Fatima Aidil-Carvalho, Ana Caulino-Rocha, Joaquim Alexandre Ribeiro, Diana Cunha-Reis

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Abstract

Novelty influences hippocampal-dependent memory through metaplasticity. Mismatch novelty detection activates the human hippocampal CA1 area and enhances rat hippocampal-dependent learning and exploration. Remarkably, mismatch novelty training (NT) also enhances rodent hippocampal synaptic plasticity while inhibition of VIP interneurons promotes rodent exploration. Since VIP, acting on VPAC₁ receptors (Rs), restrains hippocampal LTP and depotentiation by modulating disinhibition, we now investigated the impact of NT on VPAC₁ modulation of hippocampal synaptic plasticity in male Wistar rats. NT enhanced both CA1 hippocampal LTP and depotentiation unlike exploring an empty holeboard (HT) or a fixed configuration of objects (FT). Blocking VIP VPAC₁Rs with PG 97269 (100 nM) enhanced both LTP and depotentiation in naïve animals, but this effect was less effective in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). HT and FT animals showed mildly enhanced synaptic VPAC₁R levels, but neither VIP nor VPAC₁R levels were altered in NT animals. Conversely, NT enhanced the GluA1/GluA2 AMPAR ratio and gephyrin synaptic content but not PSD-95 excitatory synaptic marker. In conclusion, NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons while upregulation of VIP VPAC₁Rs is associated with the maintenance of VIP control of LTP in FT and HT animals. This suggests VIP receptor ligands may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs.

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错配新奇探索训练改变了雄性大鼠 VPAC1 受体介导的内源性 VIP 对海马突触可塑性的调节作用

新奇感通过元弹塑性影响海马依赖性记忆错配新奇事物检测激活了人类海马CA1区，并增强了大鼠海马依赖性学习和探索。值得注意的是，错配新奇事物训练（NT）也能增强啮齿类动物海马突触的可塑性，而抑制 VIP 中间神经元则能促进啮齿类动物的探索。由于VIP作用于VPAC1受体（Rs），通过调节抑制作用来抑制海马LTP和去势，我们现在研究了NT对雄性Wistar大鼠海马突触可塑性的VPAC1调节作用的影响。与探索空洞板（HT）或固定物体配置（FT）不同，NT能增强CA1海马的LTP和去延缓。用PG 97269（100 nM）阻断VIP VPAC1R可增强天真动物的LTP和去延时，但这种效果在NT大鼠中不那么有效。在暴露于空旷环境（HT）的动物中，内源性 VIP 对 LTP 的调节没有改变。HT和FT动物的突触VPAC1R水平轻度升高，但NT动物的VIP和VPAC1R水平均无变化。相反，NT提高了GluA1/GluA2 AMPAR比率和ephyrin突触含量，但没有提高PSD-95兴奋性突触标记。总之，NT通过重塑大脑回路调节抑制及其由表达VIP的海马中间神经元的控制来影响海马突触可塑性，而VIP VPAC1Rs的上调与维持FT和HT动物LTP的VIP控制有关。这表明，VIP受体配体可能与老年或癫痫患者的认知恢复疗法有关，因为在这些患者中，LTP/LTD会发生失衡。

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来源期刊

Journal of Neuroscience Research 医学-神经科学

CiteScore

9.50

自引率

2.40%

发文量

145

审稿时长

1 months

期刊介绍： The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology. The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.