Sánchez-Pérez Ana M, Arnal-Vicente Isabel, Santos Fabio N, Pereira Celia W, ElMlili Nisrin, Sanjuan Julio, Ma Sherie, Gundlach Andrew L, Olucha-Bordonau Francisco E
Departamento de Medicina, Universitat Jaume I, 12071, Castellón, Spain.
J Comp Neurol. 2015 Mar 1;523(4):565-88. doi: 10.1002/cne.23687. Epub 2014 Dec 19.
Projections from the nucleus incertus (NI) to the septum have been implicated in the modulation of hippocampal theta rhythm. In this study we describe a previously uncharacterized projection from the septum to the NI, which may provide feedback modulation of the ascending circuitry. Fluorogold injections into the NI resulted in retrograde labeling in the septum that was concentrated in the horizontal diagonal band and areas of the posterior septum including the septofimbrial and triangular septal nuclei. Double-immunofluorescent staining indicated that the majority of NI-projecting septal neurons were calretinin-positive and some were parvalbumin-, calbindin-, or glutamic acid decarboxylase (GAD)-67-positive. Choline acetyltransferase-positive neurons were Fluorogold-negative. Injection of anterograde tracers into medial septum, or triangular septal and septofimbrial nuclei, revealed fibers descending to the supramammillary nucleus, median raphe, and the NI. These anterogradely labeled varicosities displayed synaptophysin immunoreactivity, indicating septal inputs form synapses on NI neurons. Anterograde tracer also colocalized with GAD-67-positive puncta in labeled fibers, which in some cases made close synaptic contact with GAD-67-labeled NI neurons. These data provide evidence for the existence of an inhibitory descending projection from medial and posterior septum to the NI that provides a "feedback loop" to modulate the comparatively more dense ascending NI projections to medial septum and hippocampus. Neural processes and associated behaviors activated or modulated by changes in hippocampal theta rhythm may depend on reciprocal connections between ascending and descending pathways rather than on unidirectional regulation via the medial septum.
不确定核（NI）向隔区的投射与海马θ节律的调节有关。在本研究中，我们描述了一种以前未被描述的从隔区到NI的投射，它可能对上行神经回路提供反馈调节。向NI注射荧光金导致隔区出现逆行标记，标记集中在水平对角带和后隔区，包括隔纤维核和三角隔核。双重免疫荧光染色表明，投射到NI的隔区神经元大多数是钙视网膜蛋白阳性，一些是小白蛋白、钙结合蛋白或谷氨酸脱羧酶（GAD）-67阳性。胆碱乙酰转移酶阳性神经元为荧光金阴性。将顺行示踪剂注入内侧隔区、三角隔核或隔纤维核，显示纤维向下延伸至乳头体上核、中缝正中核和NI。这些顺行标记的曲张体显示突触素免疫反应性，表明隔区输入在NI神经元上形成突触。顺行示踪剂在标记纤维中也与GAD-67阳性小点共定位，在某些情况下，这些小点与GAD-67标记的NI神经元形成紧密的突触接触。这些数据为存在从内侧和后隔区到NI的抑制性下行投射提供了证据，该投射提供了一个“反馈回路”，以调节相对更密集的从NI到内侧隔区和海马的上行投射。由海马θ节律变化激活或调节的神经过程和相关行为可能取决于上行和下行通路之间的相互连接，而不是通过内侧隔区的单向调节。
