Blazon Maxwell, LaCarubba Brianna, Bunda Alexandra, Czepiel Natalie, Mallat Shayna, Londrigan Laura, Andrade Arturo
Department of Biological Sciences, University of New Hampshire. 46 College Road, 245 Rudman Hall. Durham, NH, USA.
OBM Neurobiol. 2021;5(1). doi: 10.21926/obm.neurobiol.2101083. Epub 2021 Jan 12.
N-type (Ca2.2) calcium channels are key for action potential-evoked transmitter release in the peripheral and central nervous system. Previous studies have highlighted the functional relevance of N-type calcium channels at both the peripheral and central level. In the periphery, the N-type calcium channels regulate nociceptive and sympathetic responses. At the central level, N-type calcium channels have been linked to aggression, hyperlocomotion, and anxiety. Among the areas of the brain that are involved in anxiety are the basolateral amygdala, medial prefrontal cortex, and ventral hippocampus. These three areas share similar characteristics in their neuronal circuitry, where pyramidal projection neurons are under the inhibitory control of a wide array of interneurons including those that express the peptide cholecystokinin. This type of interneuron is well-known to rely on N-type calcium channels to release GABA in the hippocampus, however, whether these channels control GABA release from cholecystokinin-expressing interneurons in the basolateral amygdala and medial prefrontal cortex is not known. Here, using mouse models to genetically label cholecystokinin-expressing interneurons and electrophysiology, we found that in the basolateral amygdala, N-type calcium channels control ~50% of GABA release from these neurons onto pyramidal cells. By contrast, in the medial prefrontal cortex N-type calcium channels are functionally absent in synapses of cholecystokinin-expressing interneurons, but control ~40% of GABA release from other types of interneurons. Our findings provide insights into the precise localization of N-type calcium channels in interneurons of brain areas related to anxiety.
N型（Ca2.2）钙通道对于外周和中枢神经系统中动作电位诱发的神经递质释放至关重要。先前的研究强调了N型钙通道在外周和中枢水平上的功能相关性。在外周，N型钙通道调节伤害性感受和交感反应。在中枢水平，N型钙通道与攻击行为、运动亢进和焦虑有关。参与焦虑的脑区包括基底外侧杏仁核、内侧前额叶皮质和腹侧海马体。这三个区域在其神经元回路中具有相似的特征，其中锥体细胞投射神经元受到包括表达肽胆囊收缩素的中间神经元在内的多种中间神经元的抑制性控制。众所周知，这种类型的中间神经元在海马体中依赖N型钙通道释放γ-氨基丁酸（GABA），然而，这些通道是否控制基底外侧杏仁核和内侧前额叶皮质中表达胆囊收缩素的中间神经元释放GABA尚不清楚。在这里，我们使用小鼠模型对表达胆囊收缩素的中间神经元进行基因标记并结合电生理学方法，发现在基底外侧杏仁核中，N型钙通道控制了这些神经元向锥体细胞释放约50%的GABA。相比之下，在内侧前额叶皮质中，表达胆囊收缩素的中间神经元的突触在功能上不存在N型钙通道，但控制了其他类型中间神经元约40%的GABA释放。我们的研究结果为N型钙通道在与焦虑相关脑区的中间神经元中的精确定位提供了见解。
