Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690-2nd Floor, 90610-000 Porto Alegre, RS, Brazil.
Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690-2nd Floor, 90610-000 Porto Alegre, RS, Brazil.
Neurobiol Learn Mem. 2021 Apr;180:107423. doi: 10.1016/j.nlm.2021.107423. Epub 2021 Mar 9.
Social recognition memory (SRM) forms the basis of social relationships of animals. It is essential for social interaction and adaptive behavior, reproduction and species survival. Evidence demonstrates that social deficits of psychiatric disorders such as autism and schizophrenia are caused by alterations in SRM processing by the hippocampus and amygdala. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its receptors PAC1, VPAC1 and VPAC2 are highly expressed in these regions. PACAP is a pleiotropic neuropeptide that modulates synaptic function and plasticity and is thought to be involved in social behavior. PACAP signaling also stimulates the nitric oxide (NO) production and targets outcomes to synapses. In the present work, we investigate the effect of the infusion of PACAP-38 (endogenous neuropeptide and potent stimulator of adenylyl cyclase), PACAP 6-38 (PAC1/VPAC2 receptors antagonist) and S-Nitroso-N-acetyl-DL-penicillamine (SNAP, NO donor) in the CA1 region of the hippocampus and in the basolateral amygdala (BLA) on the consolidation of SRM. For this, male Wistar rats with cannulae implanted in CA1 or in BLA were subjected to a social discrimination paradigm, which is based on the natural ability of rodents to investigate unfamiliar conspecifics more than familiar one. In the sample phase (acquisition), animals were exposed to a juvenile conspecific for 1 h. Immediately, 60 or 150 min after, animals received one of different pharmacological treatments. Twenty-four hours later, they were submitted to a 5 min retention test in the presence of the previously presented juvenile (familiar) and a novel juvenile. Animals that received infusions of PACAP 6-38 (40 pg/side) into CA1 immediately after the sample phase or into BLA immediately or 60 min after the sample phase were unable to recognize the familiar juvenile during the retention test. This impairment was abolished by the coinfusion of PACAP 6-38 plus SNAP (5 μg/side). These results show that the blockade of PACAP/PAC1/VPAC2 signaling in the CA1 and BLA during a restricted post-acquisition time window impairs the consolidation of SRM and that the SNAP is able to abolish this deficit. Findings like this could potentially be used in the future to influence studies of psychiatric disorders involving social behavior.
社会识别记忆 (SRM) 是动物社会关系的基础。它对于社交互动和适应行为、繁殖和物种生存至关重要。有证据表明，自闭症和精神分裂症等精神疾病的社交缺陷是由海马体和杏仁核的 SRM 处理改变引起的。垂体腺苷酸环化酶激活肽 (PACAP) 及其受体 PAC1、VPAC1 和 VPAC2 在这些区域高度表达。PACAP 是一种多效神经肽，可调节突触功能和可塑性，被认为与社交行为有关。PACAP 信号还刺激一氧化氮 (NO) 的产生，并将作用靶点指向突触。在本工作中，我们研究了 PACAP-38（内源性神经肽和腺苷酸环化酶的有效刺激物）、PACAP 6-38（PAC1/VPAC2 受体拮抗剂）和 S-亚硝基-N-乙酰-DL-青霉胺 (SNAP，NO 供体) 在海马 CA1 区和基底外侧杏仁核 (BLA) 中的输注对 SRM 巩固的影响。为此，将植入 CA1 或 BLA 导管的雄性 Wistar 大鼠置于社交辨别范式下，该范式基于啮齿动物自然的能力，即比熟悉的个体更喜欢探索不熟悉的同种个体。在样本阶段（获取），动物暴露于幼年同种个体 1 小时。立即在样本阶段后 60 或 150 分钟后，动物接受不同的药理学处理之一。24 小时后，它们在之前呈现的幼年（熟悉）和新的幼年存在的情况下接受 5 分钟的保留测试。在样本阶段后立即或样本阶段后 60 分钟将 PACAP 6-38（40pg/侧）输注到 CA1 或 BLA 的动物在保留测试中无法识别熟悉的幼年。这种损伤被 PACAP 6-38 与 SNAP（5μg/侧）共输注所消除。这些结果表明，在限定的获取后时间窗口内，CA1 和 BLA 中 PACAP/PAC1/VPAC2 信号的阻断会损害 SRM 的巩固，而 SNAP 能够消除这种缺陷。这种发现将来可能被用于影响涉及社交行为的精神疾病的研究。
