Gil-Miravet Isis, Mañas-Ojeda Aroa, Ros-Bernal Francisco, Castillo-Gómez Esther, Albert-Gascó Hector, Gundlach Andrew L, Olucha-Bordonau Francisco E
Unitat Predepartamental de Medicina, Facultat de Ciències de la Salut, Universitat Jaume I, Castelló de la Plana, Spain.
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain.
Front Neuroanat. 2021 Mar 18;15:637922. doi: 10.3389/fnana.2021.637922. eCollection 2021.
Telencephalic cognitive and emotional circuits/functions are strongly modulated by subcortical inputs. The main focus of past research on the nature of this modulation has been on the widespread monoamine projections to the telencephalon. However, the (NI) of the pontine tegmentum provides a strong GABAergic and peptidergic innervation of the hippocampus, basal forebrain, amygdala, prefrontal cortex, and related regions; and represents a parallel source of ascending modulation of cognitive and emotional domains. NI GABAergic neurons express multiple peptides, including neuromedin-B, cholecystokinin, and relaxin-3, and receptors for stress and arousal transmitters, including corticotrophin-releasing factor and orexins/hypocretins. A functional relationship exists between NI neurons and their associated peptides, relaxin-3 and neuromedin-B, and hippocampal theta rhythm, which in turn, has a key role in the acquisition and extinction of declarative and emotional memories. Furthermore, RXFP3, the cognate receptor for relaxin-3, is a G protein-coupled receptor, and its activation inhibits the cellular accumulation of cAMP and induces phosphorylation of ERK, processes associated with memory formation in the hippocampus and amygdala. Therefore, this review summarizes the role of NI transmitter systems in relaying stress- and arousal-related signals to the higher neural circuits and processes associated with memory formation and retrieval.
端脑的认知和情感回路/功能受到皮层下输入的强烈调节。过去关于这种调节本质的研究主要集中在广泛的单胺能投射到端脑。然而，脑桥被盖的（NI）向海马体、基底前脑、杏仁核、前额叶皮层及相关区域提供强大的γ-氨基丁酸能和肽能神经支配；并且代表了认知和情感领域上行调节的平行来源。NI的γ-氨基丁酸能神经元表达多种肽，包括神经介素B、胆囊收缩素和松弛素-3，以及应激和觉醒递质的受体，包括促肾上腺皮质激素释放因子和食欲素/下丘脑分泌素。NI神经元与其相关肽、松弛素-3和神经介素B以及海马θ节律之间存在功能关系，而海马θ节律反过来在陈述性记忆和情感记忆的获取与消退中起关键作用。此外，松弛素-3的同源受体RXFP3是一种G蛋白偶联受体，其激活会抑制环磷酸腺苷的细胞积累并诱导细胞外信号调节激酶的磷酸化，这些过程与海马体和杏仁核中的记忆形成有关。因此，本综述总结了NI递质系统在将应激和觉醒相关信号传递到与记忆形成和检索相关的高级神经回路和过程中的作用。
