Fujisawa Shigeyoshi, Yamada Maki K, Nishiyama Nobuyoshi, Matsuki Norio, Ikegaya Yuji
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Biophys J. 2004 Mar;86(3):1820-8. doi: 10.1016/S0006-3495(04)74249-6.
Oscillatory activity and its nonlinear dynamics are of fundamental importance for information processing in the central nervous system. Here we show that in aperiodic oscillations, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, enhances the accuracy of action potentials in terms of spike reliability and temporal precision. Cultured hippocampal neurons displayed irregular oscillations of membrane potential in response to sinusoidal 20-Hz somatic current injection, yielding wobbly orbits in the phase space, i.e., a strange attractor. Brief application of BDNF suppressed this unpredictable dynamics and stabilized membrane potential fluctuations, leading to rhythmical firing. Even in complex oscillations induced by external stimuli of 40 Hz (gamma) on a 5-Hz (theta) carrier, BDNF-treated neurons generated more precisely timed spikes, i.e., phase-locked firing, coupled with theta-phase precession. These phenomena were sensitive to K252a, an inhibitor of tyrosine receptor kinases and appeared attributable to BDNF-evoked Na(+) current. The data are the first indication of pharmacological control of endogenous chaos. BDNF diminishes the ambiguity of spike time jitter and thereby might assure neural encoding, such as spike timing-dependent synaptic plasticity.
振荡活动及其非线性动力学对于中枢神经系统中的信息处理至关重要。在此我们表明,在非周期性振荡中,神经营养因子家族的成员脑源性神经营养因子(BDNF)在动作电位的准确性方面,即在动作电位的可靠性和时间精度方面有所提高。培养的海马神经元在响应正弦20赫兹体电流注入时表现出膜电位的不规则振荡,在相空间中产生不稳定的轨迹,即一个奇怪吸引子。短暂应用BDNF抑制了这种不可预测的动力学并稳定了膜电位波动,导致节律性放电。即使在由5赫兹(θ)载波上的40赫兹(γ)外部刺激诱导的复杂振荡中,经BDNF处理的神经元也会产生更精确计时的动作电位,即锁相放电,并伴有θ相进动。这些现象对酪氨酸受体激酶抑制剂K252a敏感,并且似乎归因于BDNF诱发的Na(+)电流。这些数据是内源性混沌药理学控制的首个迹象。BDNF减少了动作电位时间抖动的不确定性,从而可能确保神经编码,如动作电位时间依赖性突触可塑性。