药物依赖是当前神经科学研究的热点问题,其病因错综复杂。近年来,药物依赖与ATP结合盒B亚家族成员1转运蛋白(ATP-binding cassette subfamily B member 1 transporter,ABCB1)基因多态性的关系越来越受到关注,特别是位于26号外显子区域的3435C>T。该文就阿片类药物依赖和镇痛耐受与ABCB1基因多态性的关系进行综述,对于深入阐明药物依赖的机制以及指导美沙酮个体化治疗具有重要意义。
Acetylcholine(ACh)is an important neuromod-ulator in various cognitive functions.However,it is unclear how ACh influences neural circuit dynamics by altering cellular properties.Here,we investigated how ACh influ-ences reverberatory activity in cultured neuronal networks.We found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses,but to a much lesser extent at high doses.Moreover,high doses of ACh caused a longer duration of evoked reverberation,and a higher occur-rence of spontaneous activity.With whole-cell recording from single neurons,we found that ACh inhibited excita-tory postsynaptic currents(EPSCs)while elevating neu-ronal firing in a dose-dependent manner.Furthermore,all ACh-induced cellular and network changes were blocked by muscarinic,but not nicotinic receptor antagonists.With computational modeling,we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental observations.Thus,ACh modulates network dynamics in a biphasic fashion,probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.
Xiao-Wei LiYi RenDong-Qing ShiLei QiFang XuYanyang XiaoPak-Ming LauGuo-Qiang Bi
Dear Editor,The timing of spiking activity across neurons is believed to play an important role in information coding in brain circuits1[1].At the cellular level,neurons can fire spikes with millisecond precision and the relative timing of pre-and postsynaptic spikes can determine the direction and extent of synaptic modification[2].When such spike-timing-dependent plasticity(STDP)and other physiological and anatomical properties are implemented in theoretical models,the simulated networks of interconnected spiking neurons exhibit neuronal groups with stereotypical time-locked spatiotemporal firing patterns with millisecond temporal precision[3].
