Spatial learning and memory processes depend on anatomical and functional interactions between the hippocampus and the entorhinal cortex. A key neurophysiological component of these processes is hippocampal theta rhythm, which can be driven from subcortical areas including the pontine nucleus incertus (NI). The NI contains the largest population of neurons that produce and presumably release the neuropeptide, relaxin-3, which acts via the Gi/o-protein-coupled receptor, RXFP3. NI activation induces general arousal including hippocampal theta, and inactivation induces impairment of spatial memory acquisition or retrieval. The primary aim of this study was to map the NI/relaxin-3 innerva-tion of the parahippocampal cortex, including the medial and lateral entorhinal cortex, endopiriform cortex, perirhinal, postrhinal and ectorhinal cortex, the amygdalohippocampal transition area and posteromedial cortical amygdala. Retrograde tracer injections were placed in different parts of the medial and lateral entorhinal cortex, which produced prominent retrograde labeling in the ipsilateral NI and some labeling in the contralateral NI. Anterograde tracer injections into the NI and im-munostaining for relaxin-3 produced fiber labeling in deep layers of all parahippocampal areas and some dispersed fibers in superficial layers. Double-labeling studies revealed that both hippocam-palprojecting and calcium-binding protein-positive (presumed GABAergic) neurons received a relax-in-3 NI innervation. Some of these fibers also displayed synaptophysin immunoreactivity, consistent with the presence of the peptide at synapses; and relaxin-3-positive fibers containing synaptophysin boutonlike staining were frequently observed in contact with hippocampal-projecting or calcium-binding protein-positive neuronal somata and more distal elements. Finally, in situ hybridization stud-ies revealed that entorhinal neurons in the superficial layers, and to a lesser extent in deep layers, con-tain RXFP3 mRNA. Together, our data support functional actions of the NI/relaxin-3-parahippocampal innervation on processes related to memory, spatial navigation and contextual analysis.

中文翻译：

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从大鼠不活动核到大鼠海马旁皮质的Relaxinin-3神经支配

空间学习和记忆过程取决于海马体和内嗅皮层之间的解剖和功能相互作用。这些过程的关键神经生理学成分是海马θ节律，其可以由皮层下区域驱动，包括桥脑不育核（NI）。NI包含最大数量的神经元，这些神经元产生并可能释放神经肽松弛素3，该松弛素通过Gi / o蛋白偶联受体RXFP3起作用。NI激活引起包括海马theta在内的全面觉醒，而失活则引起空间记忆获取或恢复受损。这项研究的主要目的是绘制海马旁皮层的NI / relaxin-3神经分布图，包括内侧和外侧内嗅皮层，内膜状皮层，周围，上皮和后上皮层，杏仁核海马过渡区和后内侧皮质杏仁核。逆行示踪剂注射放置在内侧和外侧内嗅皮层的不同部分，在同侧NI产生明显的逆行标记，在对侧NI产生一些标记。向NI注射顺铂示踪剂并进行放松素3免疫染色可在所有海马旁区域的深层中产生纤维标记，并在表层中产生一些分散的纤维。双重标记研究表明，海马凸轮投射和钙结合蛋白阳性（推测为GABA能）神经元均接受了3项NI神经松弛。这些纤维中的一些还表现出突触素免疫反应性，这与突触中肽的存在相一致。经常在与海马投射或钙结合蛋白阳性神经元躯体及更多远端元件接触时，观察到含有突触素boutonlike染色的松弛素3阳性纤维和松弛素3阳性纤维。最后，原位杂交研究表明，内在神经元在表层，而在较小程度上在深层，则包含RXFP3 mRNA。总之，我们的数据支持NI / relaxin-3-旁海马神经支配在与记忆，空间导航和上下文分析有关的过程中的功能性作用。