Leung L Stan, Yim Chi Yiu Conrad
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
Hippocampus. 2025 Jan;35(1):e23660. doi: 10.1002/hipo.23660.
The hypothesis that the hippocampal theta rhythm consists of inhibitory postsynaptic potentials (IPSPs) was critical for understanding the theta rhythm. The dominant views in the early 1980s were that intracellularly recorded theta consisted of excitatory postsynaptic potentials (EPSPs) with little participation by IPSPs, and that IPSPs generated a closed monopolar field in the hippocampus. I (Leung) conceived of a new model for generation of the hippocampal theta rhythm, with theta-rhythmic IPSPs as an essential component, and thus sought to reinvestigate the relation between theta and IPSPs quantitatively with intracellular and extracellular recordings. The intracellular recordings were performed by Leung and Yim in the laboratory of Kris Krnjević at McGill University. Using protocols of passing steady-state holding currents and injection of chloride ions, the intracellular theta and IPSP in a CA1 neuron typically showed the same reversal potential and correlated change in amplitude. Low-intensity stimulation of the alveus evoked an antidromic action potential in CA1 neurons, identifying them as pyramidal cells with output axons in the alveus, which then activated a feedback IPSP with almost no excitatory component. Theta-rhythmic somatic inhibition, together with phase-shifted theta-rhythmic distal apical dendritic excitation were proposed as the two dipoles that generate a gradual extracellular theta phase shift in the CA1 apical dendritic layer. The distal apical excitation driven by the entorhinal cortex was proposed to be atropine-resistant and dominated during walking in rats. Other than serving a conventional role in limiting excitation, rhythmic proximal inhibition and distal dendritic excitation provide varying phasic modulation along the soma-dendritic axis of pyramidal cells, resulting in theta phase-dependent synaptic plasticity and gamma oscillations, which are likely involved in cognitive processing.
海马体θ节律由抑制性突触后电位（IPSPs）组成这一假说对于理解θ节律至关重要。20世纪80年代初的主流观点是，细胞内记录到的θ节律由兴奋性突触后电位（EPSPs）组成，IPSPs参与较少，且IPSPs在海马体中产生一个封闭的单极场。我（梁）构想了一种新的海马体θ节律产生模型，其中θ节律性IPSPs是一个重要组成部分，因此试图通过细胞内和细胞外记录定量重新研究θ与IPSPs之间的关系。细胞内记录由梁和严在麦吉尔大学克里斯·克尔涅维奇的实验室进行。使用通过稳态保持电流和注入氯离子的实验方案，CA1神经元中的细胞内θ和IPSP通常表现出相同的反转电位和幅度的相关变化。低强度刺激海马槽在CA1神经元中诱发了一个逆向动作电位，将它们识别为在海马槽中有输出轴突的锥体细胞，然后激活了一个几乎没有兴奋性成分的反馈IPSP。θ节律性体细胞抑制，以及相位偏移的θ节律性远端顶端树突兴奋被提出作为在CA1顶端树突层中产生逐渐的细胞外θ相位偏移的两个偶极。由内嗅皮层驱动的远端顶端兴奋被认为是对阿托品有抗性的，并且在大鼠行走时占主导地位。除了在限制兴奋方面发挥传统作用外，节律性近端抑制和远端树突兴奋沿着锥体细胞的胞体-树突轴提供不同的相位调制，导致θ相位依赖性突触可塑性和γ振荡，这可能参与认知加工。
