Université Paris Descartes, Inserm UMR1266, Institute of Psychiatry and Neuroscience of Paris, Team Synaptic Plasticity and Neural Networks, Paris, France.
Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
J Gen Physiol. 2020 Apr 6;152(4). doi: 10.1085/jgp.201912462.
Recent studies have revealed that hippocampal area CA2 plays an important role in hippocampal network function. Disruption of this region has been implicated in neuropsychiatric disorders. It is well appreciated that cholinergic input to the hippocampus plays an important role in learning and memory. While the effect of elevated cholinergic tone has been well studied in areas CA1 and CA3, it remains unclear how changes in cholinergic tone impact synaptic transmission and the intrinsic properties of neurons in area CA2. In this study, we applied the cholinergic agonist carbachol and performed on-cell, whole-cell, and extracellular recordings in area CA2. We observed that under conditions of high cholinergic tone, CA2 pyramidal neurons depolarized and rhythmically fired bursts of action potentials. This depolarization depended on the activation of M1 and M3 cholinergic receptors. Furthermore, we examined how the intrinsic properties and action-potential firing were altered in CA2 pyramidal neurons treated with 10 µM carbachol. While this intrinsic burst firing persisted in the absence of synaptic transmission, bursts were shaped by synaptic inputs in the intact network. We found that both excitatory and inhibitory synaptic transmission were reduced upon carbachol treatment. Finally, we examined the contribution of different channels to the cholinergic-induced changes in neuronal properties. We found that a conductance from Kv7 channels partially contributed to carbachol-induced changes in resting membrane potential and membrane resistance. We also found that D-type potassium currents contributed to controlling several properties of the bursts, including firing rate and burst kinetics. Furthermore, we determined that T-type calcium channels and small conductance calcium-activated potassium channels play a role in regulating bursting activity.
最近的研究表明，海马区 CA2 在海马网络功能中起着重要作用。该区域的破坏与神经精神疾病有关。人们清楚地认识到，胆碱能输入到海马体在学习和记忆中起着重要作用。虽然升高的胆碱能音调的影响在 CA1 和 CA3 区域得到了很好的研究，但尚不清楚胆碱能音调的变化如何影响突触传递和 CA2 区神经元的固有特性。在这项研究中，我们应用了胆碱能激动剂卡巴胆碱，并在 CA2 区进行了细胞膜片钳、全细胞膜片钳和细胞外记录。我们观察到，在高胆碱能条件下，CA2 锥体神经元去极化并节律性地爆发动作电位。这种去极化依赖于 M1 和 M3 胆碱能受体的激活。此外，我们研究了在 10 µM 卡巴胆碱处理的 CA2 锥体神经元中，内在特性和动作电位发放是如何改变的。虽然这种内在爆发性放电在没有突触传递的情况下持续存在，但在完整网络中，爆发被突触输入所塑造。我们发现，在卡巴胆碱处理后，兴奋性和抑制性突触传递都减少了。最后，我们研究了不同通道对胆碱能诱导的神经元特性变化的贡献。我们发现 Kv7 通道的电导部分有助于卡巴胆碱诱导的静息膜电位和膜电阻的变化。我们还发现 D 型钾电流有助于控制爆发的几个特性，包括发放率和爆发动力学。此外，我们确定 T 型钙通道和小电导钙激活钾通道在调节爆发活动中起作用。
