Laboratory of Neuroscience, Department of Psychology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Pl. Feijoo s/n, 33003 Oviedo, Spain; Dept. Neurophysiology. Medical Faculty, Ruhr-University Bochum. Universitätsstraße, 150. Building MA 01/551, 44780 Bochum, Germany.
Laboratory of Neuroscience, Department of Psychology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, Pl. Feijoo s/n, 33003 Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain.
Neurobiol Learn Mem. 2022 Jan;187:107561. doi: 10.1016/j.nlm.2021.107561. Epub 2021 Nov 25.
The neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y receptor (YR) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on YR remain unclear.
Here, we examined the involvement of the hippocampal NPY YR in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions.
The acute blockade of NPY YR significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies.
These findings suggest that the NPY hippocampal system, through its YR receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by YR modulation of long-term potentiation and long-term depression.
神经肽 Y（NPY）广泛分布于中枢神经系统（CNS），与神经保护功能有关。NPY 似乎是对抗滥用药物和神经退行性疾病引起的脑损伤和认知障碍的重要组成部分，NPY 及其 Y 受体（YR）在海马体中高度表达，这对于学习和记忆至关重要。我们最近证明了它对认知功能的影响；然而，NPY 通过作用于 YR 调节空间记忆的具体机制和涉及的脑区仍不清楚。
在这里，我们通过向大鼠背侧海马双侧给予选择性拮抗剂 BIIE0246，检查海马 NPY YR 在空间记忆和相关脑代谢变化中的作用。为了进一步评估记忆功能与神经元活动之间的关系，我们分析了作为边缘和非边缘脑区氧化代谢能力指标的线粒体酶细胞色素 c 氧化酶（CCO）的区域表达。
NPY YR 的急性阻断显著改善了在 Morris 水迷宫中接受训练的大鼠的空间记忆回忆，这与空间记忆处理区域的代谢活动变化相匹配。具体来说，在背侧海马体的齿状回和腹侧海马体的 CA1 亚区、前额叶皮层的下边缘区和乳头体中发现了 CCO 活性变化。
这些发现表明，海马 NPY 系统通过其 YR 受体影响空间记忆回忆（检索），并对与联想学习相关的大脑激活模式施加控制，可能通过 YR 调节长时程增强和长时程抑制来介导。
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