Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, UNSW Sydney, Sydney, New South Wales, Australia.
J Neurophysiol. 2021 May 1;125(5):1825-1832. doi: 10.1152/jn.00657.2019. Epub 2021 Apr 14.
Neurons in the lateral septum (LS) integrate glutamatergic synaptic inputs, primarily from hippocampus, and send inhibitory projections to brain regions involved in reward and the generation of motivated behavior. Motivated learning and drugs of abuse have been shown to induce long-term changes in the strength of glutamatergic synapses in the LS, but the cellular mechanisms underlying long-term synaptic modification in the LS are poorly understood. Here, we examined synaptic transmission and long-term depression (LTD) in brain slices prepared from male and female C57BL/6 mice. No sex differences were observed in whole cell patch-clamp recordings of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R)- and -methyl-d-aspartate receptor (NMDA-R)-mediated currents. Low-frequency stimulation of the fimbria fiber bundle (1 Hz 15 min) induced LTD of the LS field excitatory postsynaptic potential (fEPSP). Induction of LTD was blocked by the NMDA-R antagonist (d)-2-amino-5-phosphonovaleric acid (APV), but not the selective antagonist of GluN2B-containing NMDA-Rs ifenprodil. These results demonstrate the NMDA-R dependence of LTD in the LS. The LS is a sexually dimorphic structure, and sex differences in glutamatergic transmission have been reported in vivo; our results suggest sex differences observed in vivo result from network activity rather than intrinsic differences in glutamatergic transmission. The lateral septum (LS) integrates information from hippocampus and other regions to provide context-dependent (top down or higher order) regulation of mood and motivated behavior. Learning and drugs of abuse induce long-term changes in the strength of glutamatergic projections to the LS; however, the cellular mechanisms underlying such changes are poorly understood. Here, we demonstrate there are no apparent sex differences in fast excitatory transmission and that long-term synaptic depression in the LS is NMDA-R dependent.
外侧隔核（LS）整合谷氨酸能突触输入，主要来自海马体，并向参与奖励和产生动机行为的脑区发出抑制性投射。已表明动机学习和滥用药物会导致 LS 中谷氨酸能突触强度的长期变化，但 LS 中长时程突触修饰的细胞机制知之甚少。在这里，我们检查了来自雄性和雌性 C57BL/6 小鼠脑片的突触传递和长时程抑郁（LTD）。在全细胞膜片钳记录中未观察到 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPA-R）和 -甲基-d-天冬氨酸受体（NMDA-R）介导的电流的性别差异。纤维束束（1 Hz 15 min）的低频刺激诱导 LS 场兴奋性突触后电位（fEPSP）的 LTD。LTD 的诱导被 NMDA-R 拮抗剂（d）-2-氨基-5-磷戊酸（APV）阻断，但不是含有 GluN2B 的 NMDA-R 选择性拮抗剂ifenprodil 阻断。这些结果表明 LS 中的 LTD 依赖于 NMDA-R。LS 是一种性别二态结构，体内已报道谷氨酸能传递存在性别差异；我们的结果表明，体内观察到的性别差异源自网络活动，而不是谷氨酸能传递的内在差异。外侧隔核（LS）整合来自海马体和其他区域的信息，以提供情绪和动机行为的上下文相关（自上而下或更高阶）调节。学习和滥用药物会导致谷氨酸能投射到 LS 的强度发生长期变化；然而，这种变化的细胞机制知之甚少。在这里，我们证明在 LS 中没有明显的性别差异在快速兴奋性传递中，并且 LS 中的长时程突触抑制依赖于 NMDA-R。
