Stinson Hannah E, Ninan Ipe
Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.
Heliyon. 2024 Sep 19;10(19):e38192. doi: 10.1016/j.heliyon.2024.e38192. eCollection 2024 Oct 15.
The ascending neuromodulatory pathway from the median raphe nucleus (MRN) extends widely throughout midline/para-midline regions and robustly innervates the hippocampus. This neuromodulatory pathway is believed to be critical for regulating emotional and affective behaviors. Although the MRN primarily contains serotoninergic (5-HTergic), GABAergic, and glutamatergic neurons, glutamatergic neurons expressing vesicular glutamate transporter 3 (VGLUT3) form the primary MRN input to the hippocampus. Despite the earlier demonstration of the robust MRN VGLUT3 innervation of the hippocampus, little is known about how this MRN glutamatergic input modulates synaptic transmission and plasticity in the hippocampus. Our studies show that MRN VGLUT3 neurons activate serotonin 3a receptor (5-HT3aR)-expressing GABAergic neurons, including VGLUT3-expressing neurons, at the stratum radiatum (SR)/stratum lacunosum moleculare (SLM) border. This MRN VGLUT3 neuron-mediated glutamatergic transmission onto SR/SLM 5-HT3aR neurons is negatively regulated by 5-HT through 5-HT1B receptors. In agreement with the MRN VGLUT3 neuron-mediated activation of the 5-HT3aR GABAergic neurons, activation of MRN VGLUT3 projections induces a long-lasting increase in GABAergic transmission but not glutamatergic transmission in CA1 pyramidal neurons from male but not female mice. Consistent with the MRN VGLUT3 neuron-mediated enhancement of GABAergic transmission in male mice, activation of MRN VGLUT3 projections suppresses Schaffer collateral (SC)-CA1 long-term potentiation (LTP) in male but not female mice. Thus, our results show that MRN VGLUT3 neurons modulate the dorsal hippocampus by augmenting synaptic inhibition of CA1 pyramidal neurons and by suppressing SC-CA1 LTP in a sex-specific manner.
从中缝正中核（MRN）发出的上行神经调节通路广泛延伸至中线/旁中线区域，并有力地支配海马体。这条神经调节通路被认为对调节情绪和情感行为至关重要。尽管MRN主要包含血清素能（5-羟色胺能）、γ-氨基丁酸能和谷氨酸能神经元，但表达囊泡谷氨酸转运体3（VGLUT3）的谷氨酸能神经元构成了MRN向海马体的主要输入。尽管此前已有研究表明MRN的VGLUT3对海马体有强大的神经支配，但对于这种MRN谷氨酸能输入如何调节海马体中的突触传递和可塑性，人们所知甚少。我们的研究表明，MRN的VGLUT3神经元在辐射层（SR）/分子层空泡状层（SLM）边界激活表达血清素3a受体（5-HT3aR）的γ-氨基丁酸能神经元，包括表达VGLUT3的神经元。这种由MRN的VGLUT3神经元介导的谷氨酸能传递到SR/SLM的5-HT3aR神经元上的过程，会被5-羟色胺通过5-HT1B受体进行负调节。与MRN的VGLUT3神经元介导的对5-HT3aRγ-氨基丁酸能神经元的激活一致，激活MRN的VGLUT3投射会导致雄性而非雌性小鼠CA1锥体神经元的γ-氨基丁酸能传递出现持久增加，但谷氨酸能传递没有变化。与MRN的VGLUT3神经元介导的雄性小鼠γ-氨基丁酸能传递增强一致，激活MRN的VGLUT3投射会抑制雄性而非雌性小鼠的谢弗侧支（SC）-CA1长时程增强（LTP）。因此，我们的结果表明，MRN的VGLUT3神经元通过增强对CA1锥体神经元的突触抑制以及以性别特异性方式抑制SC-CA1 LTP来调节背侧海马体。
