Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany.
Eur J Neurosci. 2011 Jul;34(1):22-30. doi: 10.1111/j.1460-9568.2011.07736.x. Epub 2011 Jun 6.
Persistent spiking activity is thought to be a cellular process involved in working memory. We have been interested in whether persistent activity also exists in cortical areas which are not involved in this memory process. To study the possible presence and the mechanisms of persistent activity in layer 5 pyramidal cells of the mouse primary somatosensory, visual and motor cortices, we used patch-clamp and calcium imaging techniques. A combination of cholinergic receptor activation and suprathreshold depolarization or sufficient extracellular stimulation leads to either a subthreshold afterdepolarization or suprathreshold persistent activity in these cortices. There is a continuum of response amplitudes depending on depolarization size. To initiate persistent activity, spikes have to be induced at a frequency of at least 20 Hz, if tested for 1 s. Acetylcholine muscarinic, but not nicotinic, receptors are important for initiating persistent activity. Persistent activity is an intrinsic cellular, not a network, phenomenon as it persists under blockade of ionotropic glutamate and GABA receptors. A rise in intracellular calcium concentration through voltage-gated calcium channels is needed for persistent activity initiation, while intracellular calcium stores are not crucial. The increased intracellular calcium concentration leads to the activation of calcium-sensitive nonspecific cationic channels. This study for the first time describes the presence and the underlying mechanisms of persistent activity in pyramidal cells of three primary sensory and motor cortex areas. These results thereby suggest that persistent activity may be a general capability of deep layer cortical pyramidal cells.
持续的尖峰活动被认为是参与工作记忆的细胞过程。我们一直感兴趣的是，在不参与这个记忆过程的皮质区域是否也存在持续活动。为了研究在小鼠初级体感、视觉和运动皮质的 5 层锥体神经元中持续活动的可能存在和机制，我们使用了膜片钳和钙成像技术。乙酰胆碱能受体的激活和阈上去极化或足够的细胞外刺激的组合导致这些皮质中的亚阈后去极化或阈上持续活动。根据去极化的大小，存在着连续的反应幅度。为了引发持续活动，在 1 秒的测试中，尖峰必须以至少 20 Hz 的频率被诱导。乙酰胆碱毒蕈碱受体，而不是烟碱受体，对于引发持续活动是重要的。持续活动是一种内在的细胞现象，而不是网络现象，因为它在离子型谷氨酸和 GABA 受体阻断的情况下仍然存在。通过电压门控钙通道的细胞内钙浓度的升高对于持续活动的引发是必需的，而细胞内钙库并不关键。增加的细胞内钙浓度导致钙敏非特异性阳离子通道的激活。本研究首次描述了在三个初级感觉和运动皮质区的锥体神经元中持续活动的存在和潜在机制。这些结果表明，持续活动可能是深层皮质锥体神经元的一种普遍能力。
