Division of Behavioral Neuroscience & Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Division of Behavioral Neuroscience & Psychiatric Disorders, Yerkes National Primate Research Center, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Neuropharmacology. 2017 Nov;126:224-232. doi: 10.1016/j.neuropharm.2017.09.013. Epub 2017 Sep 9.
The basolateral amygdala (BLA) is a key site for crossmodal association of sensory stimuli and an important relay in the neural circuitry of emotion. Indeed, the BLA receives substantial glutamatergic inputs from multiple brain regions including the prefrontal cortex and thalamic nuclei. Modulation of glutamatergic transmission in the BLA regulates stress- and anxiety-related behaviors. Serotonin (5-HT) also plays an important role in regulating stress-related behavior through activation of both pre- and postsynaptic 5-HT receptors. Multiple 5-HT receptors are expressed in the BLA, where 5-HT has been reported to modulate glutamatergic transmission. However, the 5-HT receptor subtype mediating this effect is not yet clear. The aim of this study was to use patch-clamp recordings from BLA neurons in an ex vivo slice preparation to examine 1) the effect of 5-HT on extrinsic sensory inputs, and 2) to determine if any pathway specificity exists in 5-HT regulation of glutamatergic transmission. Two independent input pathways into the BLA were stimulated: the external capsule to mimic cortical input, and the internal capsule to mimic thalamic input. Bath application of 5-HT reversibly reduced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) induced by stimulation of both pathways. The decrease was associated with an increase in the paired-pulse ratio and coefficient of variation of eEPSC amplitude, suggesting 5-HT acts presynaptically. Moreover, the effect of 5-HT in both pathways was mimicked by the selective 5-HT receptor agonist CP93129, but not by the 5-HT receptor agonist 8-OH DPAT. Similarly the effect of exogenous 5-HT was blocked by the 5-HT receptor antagonist GR55562, but not affected by the 5-HT receptor antagonist WAY 100635 or the 5-HT receptor antagonists pirenperone and MDL 100907. Together these data suggest 5-HT gates cortical and thalamic glutamatergic inputs into the BLA by activating presynaptic 5-HT receptors.
外侧杏仁核（BLA）是感觉刺激跨模态关联的关键部位，也是情绪神经回路中的重要中继站。事实上，BLA 从包括前额叶皮层和丘脑核在内的多个脑区接收大量谷氨酸能输入。BLA 中谷氨酸能传递的调制调节应激和焦虑相关行为。5-羟色胺（5-HT）通过激活突触前和突触后 5-HT 受体，在调节应激相关行为中也起着重要作用。多个 5-HT 受体在 BLA 中表达，据报道 5-HT 可调节谷氨酸能传递。然而，介导这种效应的 5-HT 受体亚型尚不清楚。本研究的目的是使用离体切片制备中的 BLA 神经元的膜片钳记录来检查 1）5-HT 对外部感觉输入的影响，2）确定 5-HT 调节谷氨酸能传递是否存在任何途径特异性。刺激 BLA 中的两个独立的输入途径：外囊以模拟皮质输入，内囊以模拟丘脑输入。5-HT 的浴应用可逆地减小了两条通路刺激诱导的诱发兴奋性突触后电流（eEPSC）的幅度。这种减少与成对脉冲比和 eEPSC 幅度的变异系数增加有关，表明 5-HT 作用于突触前。此外，选择性 5-HT 受体激动剂 CP93129 模拟了两条通路上的 5-HT 作用，而 5-HT 受体激动剂 8-OH DPAT 则不然。同样，外源性 5-HT 的作用被 5-HT 受体拮抗剂 GR55562 阻断，但不受 5-HT 受体拮抗剂 WAY 100635 或 5-HT 受体拮抗剂 pirenperone 和 MDL 100907 的影响。这些数据表明 5-HT 通过激活突触前 5-HT 受体来调节皮质和丘脑谷氨酸能传入到 BLA。
