Tateno T, Jimbo Y, Robinson H P C
Department of Physiology, Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Neuroscience. 2005;134(2):425-37. doi: 10.1016/j.neuroscience.2005.04.049.
Activation of the cholinergic innervation of the cortex has been implicated in sensory processing, learning, and memory. At the cellular level, acetylcholine both increases excitability and depresses synaptic transmission, and its effects on network firing are hard to predict. We studied the effects of carbachol, a cholinergic agonist, on network firing in cultures of rat cortical neurons, using electrode arrays to monitor the activity of large numbers of neurons simultaneously. These cultures show stable spontaneous synchronized burst firing which propagates through dense synaptic connections. Carbachol (10-50 microM), acting through muscarinic receptors, was found to induce a switch to asynchronous single-spike firing and to result in a loss of regularity and fragmentation of the burst structure. To obtain a quantitative measure of cholinergic actions on cortical networks, we applied a cluster Poisson-process model to sets of paralleled spike-trains in the presence and absence of carbachol. This revealed that the time series can be well-characterized by such a simple model, consistent with the observed 1/f(b)-like spectra (0.04<b<2.08). After applying higher concentrations of carbachol the property of the spectra shifted toward a Poisson-process (white) spectrum. These results indicate that cholinergic neurotransmitters have a strong and reliable desynchronizing action on cortical neural activity.
皮层胆碱能神经支配的激活与感觉加工、学习和记忆有关。在细胞水平上,乙酰胆碱既能增加兴奋性又能抑制突触传递,其对网络放电的影响难以预测。我们使用电极阵列同时监测大量神经元的活动,研究了胆碱能激动剂卡巴胆碱对大鼠皮层神经元培养物中网络放电的影响。这些培养物表现出稳定的自发同步爆发式放电,通过密集的突触连接进行传播。发现通过毒蕈碱受体起作用的卡巴胆碱(10 - 50微摩尔)可诱导转变为异步单峰放电,并导致爆发结构的规律性丧失和碎片化。为了获得胆碱能对皮层网络作用的定量测量,我们在有和没有卡巴胆碱的情况下,将聚类泊松过程模型应用于平行的尖峰序列集。这表明时间序列可以用这样一个简单模型很好地表征,这与观察到的1/f(b)样谱(0.04 < b < 2.08)一致。应用更高浓度的卡巴胆碱后,谱的特性向泊松过程(白色)谱转变。这些结果表明胆碱能神经递质对皮层神经活动具有强大且可靠的去同步作用。