Hofmann Mackenzie E, Nahir Ben, Frazier Charles J
Department of Pharmacodynamics, College of Pharmacy, University of Florida, JHMHC Box 100487, 1600 S.W. Archer Road, Gainesville, FL 32610, USA.
J Neurophysiol. 2006 Nov;96(5):2501-12. doi: 10.1152/jn.00310.2006. Epub 2006 Jun 28.
Hilar mossy cells represent a unique population of local circuit neurons in the hippocampus and dentate gyrus. Here we use electrophysiological techniques in acute preparations of hippocampal slices to demonstrate that depolarization of a single hilar mossy cell can produce robust inhibition of local GABAergic afferents. This depolarization-induced suppression of inhibition (DSI) can be observed as a transient reduction in frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) or as a transient reduction in amplitude of evoked IPSCs (eIPSCs). We find that DSI of eIPSCs as observed in hilar mossy cells is enhanced by activation of muscarinic acetylcholine receptors, blocked by chelation of postsynaptic calcium, and critically dependent on retrograde activation of presynaptic cannabinoid type 1 (CB1) receptors. We further report that activation of CB1 receptors on GABAergic afferents to hilar mossy cells (by either endogenous or exogenous agonists) preferentially inhibits calcium-dependent exocytosis and that endocannabinoid-dependent retrograde signaling in this system is subject to tight spatial constraints.
海马旁回苔藓细胞是海马体和齿状回中一类独特的局部回路神经元。在此，我们运用急性海马切片制备中的电生理技术，证明单个海马旁回苔藓细胞的去极化能够对局部γ-氨基丁酸能传入神经产生强烈抑制作用。这种去极化诱导的抑制作用减弱（DSI）可表现为自发性抑制性突触后电流（sIPSCs）频率的短暂降低，或诱发性抑制性突触后电流（eIPSCs）幅度的短暂降低。我们发现，海马旁回苔藓细胞中观察到的eIPSCs的DSI会因毒蕈碱型乙酰胆碱受体的激活而增强，因突触后钙的螯合而被阻断，并且严重依赖于突触前1型大麻素（CB1）受体的逆行激活。我们进一步报道，激活海马旁回苔藓细胞γ-氨基丁酸能传入神经上的CB受体（通过内源性或外源性激动剂）会优先抑制钙依赖性胞吐作用，并且该系统中内源性大麻素依赖性逆行信号传导受到严格的空间限制。
