Griesius Simonas, Richardson Amy, Kullmann Dimitri Michael
Department of Clinical Experimental and Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
Elife. 2025 Jan 31;13:RP100268. doi: 10.7554/eLife.100268.
Non-linear summation of synaptic inputs to the dendrites of pyramidal neurons has been proposed to increase the computation capacity of neurons through coincidence detection, signal amplification, and additional logic operations such as XOR. Supralinear dendritic integration has been documented extensively in principal neurons, mediated by several voltage-dependent conductances. It has also been reported in parvalbumin-positive hippocampal basket cells, in dendrites innervated by feedback excitatory synapses. Whether other interneurons, which support feed-forward or feedback inhibition of principal neuron dendrites, also exhibit local non-linear integration of synaptic excitation is not known. Here, we use patch-clamp electrophysiology, and two-photon calcium imaging and glutamate uncaging, to show that supralinear dendritic integration of near-synchronous spatially clustered glutamate-receptor mediated depolarization occurs in NDNF-positive neurogliaform cells and oriens-lacunosum moleculare interneurons in the mouse hippocampus. Supralinear summation was detected via recordings of somatic depolarizations elicited by uncaging of glutamate on dendritic fragments, and, in neurogliaform cells, by concurrent imaging of dendritic calcium transients. Supralinearity was abolished by blocking NMDA receptors (NMDARs) but resisted blockade of voltage-gated sodium channels. Blocking L-type calcium channels abolished supralinear calcium signalling but only had a minor effect on voltage supralinearity. Dendritic boosting of spatially clustered synaptic signals argues for previously unappreciated computational complexity in dendrite-projecting inhibitory cells of the hippocampus.
有人提出，锥体细胞树突的突触输入的非线性总和可通过同时检测、信号放大以及诸如异或等额外逻辑运算来提高神经元的计算能力。超线性树突整合在主要神经元中已有广泛记录，由几种电压依赖性电导介导。在由反馈兴奋性突触支配的树突中的小白蛋白阳性海马篮状细胞中也有报道。尚不清楚其他支持对主要神经元树突进行前馈或反馈抑制的中间神经元是否也表现出突触兴奋的局部非线性整合。在这里，我们使用膜片钳电生理学、双光子钙成像和谷氨酸解笼技术，来表明在小鼠海马体中的NDNF阳性神经胶质样细胞和分子层内嗅中间神经元中，近同步空间聚集的谷氨酸受体介导的去极化发生了超线性树突整合。通过记录谷氨酸在树突片段上解笼引发的体细胞去极化来检测超线性总和，并且在神经胶质样细胞中，通过同时成像树突钙瞬变来检测。通过阻断NMDA受体（NMDARs）消除了超线性，但对电压门控钠通道的阻断具有抗性。阻断L型钙通道消除了超线性钙信号，但对电压超线性只有轻微影响。空间聚集的突触信号的树突增强表明海马体中树突投射抑制性细胞存在以前未被认识到的计算复杂性。
