B. E. Alger, Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Rm 5-025, Baltimore, MD 21201, USA.
J Physiol. 2014 Jan 1;592(1):103-23. doi: 10.1113/jphysiol.2013.257428. Epub 2013 Nov 4.
Neuronal electrical oscillations in the theta (4-14 Hz) and gamma (30-80 Hz) ranges are necessary for the performance of certain animal behaviours and cognitive processes. Perisomatic GABAergic inhibition is prominently involved in cortical oscillations driven by ACh release from septal cholinergic afferents. In neocortex and hippocampal CA3 regions, parvalbumin (PV)-expressing basket cells, activated by ACh and glutamatergic agonists, largely mediate oscillations. However, in CA1 hippocampus in vitro, cholinergic agonists or the optogenetic release of endogenous ACh from septal afferents induces rhythmic, theta-frequency inhibitory postsynaptic currents (IPSCs) in pyramidal cells, even with glutamatergic transmission blocked. The IPSCs are regulated by exogenous and endogenous cannabinoids, suggesting that they arise from type 1 cannabinoid receptor-expressing (CB1R+) interneurons - mainly cholecystokinin (CCK)-expressing cells. Nevertheless, an occult contribution of PV-expressing interneurons to these rhythms remained conceivable. Here, we directly test this hypothesis by selectively silencing CA1 PV-expressing cells optogenetically with halorhodopsin or archaerhodopsin. However, this had no effect on theta-frequency IPSC rhythms induced by carbachol (CCh). In contrast, the silencing of glutamic acid decarboxylase 2-positive interneurons, which include the CCK-expressing basket cells, strongly suppressed inhibitory oscillations; PV-expressing interneurons appear to play no role. The low-frequency IPSC oscillations induced by CCh or optogenetically stimulated ACh release were also inhibited by a μ-opioid receptor (MOR) agonist, which was unexpected because MORs in CA1 are not usually associated with CCK-expressing cells. Our results reveal novel properties of an inhibitory oscillator circuit within CA1 that is activated by muscarinic agonists. The oscillations could contribute to behaviourally relevant, atropine-sensitive, theta rhythms and link cannabinoid and opioid actions functionally.
神经元电振荡在θ（4-14 Hz）和γ（30-80 Hz）范围内对于某些动物行为和认知过程的表现是必要的。室旁 GABA 能抑制在由隔区胆碱能传入释放的乙酰胆碱驱动的皮层振荡中显著参与。在新皮层和海马 CA3 区，表达 parvalbumin (PV) 的篮状细胞被乙酰胆碱和谷氨酸能激动剂激活，主要介导振荡。然而，在 CA1 海马体体外，胆碱能激动剂或光遗传学释放隔区传入的内源性乙酰胆碱诱导锥体神经元产生节律性、θ 频率抑制性突触后电流 (IPSCs)，即使阻断了谷氨酸能传递。这些 IPSCs 受外源性和内源性大麻素的调节，表明它们来自表达 1 型大麻素受体 (CB1R+) 的中间神经元 - 主要是胆囊收缩素 (CCK) 表达细胞。然而，PV 表达中间神经元对这些节律的隐匿贡献仍然是可以想象的。在这里，我们通过用光遗传学选择性沉默 CA1 PV 表达细胞来直接检验这一假设。然而，这对 carbachol (CCh) 诱导的θ 频率 IPSC 节律没有影响。相比之下，谷氨酸脱羧酶 2 阳性中间神经元（包括 CCK 表达的篮状细胞）的沉默强烈抑制抑制性振荡；PV 表达的中间神经元似乎不起作用。CCCh 或光遗传学刺激释放的乙酰胆碱诱导的低频 IPSC 振荡也被 μ-阿片受体 (MOR) 激动剂抑制，这出乎意料，因为 CA1 中的 MOR 通常与 CCK 表达细胞无关。我们的结果揭示了 CA1 内一个抑制振荡器回路的新特性，该回路被毒蕈碱激动剂激活。这些振荡可能有助于与行为相关、阿托品敏感的θ 节律，并在功能上连接大麻素和阿片类药物的作用。
