Cymbalyuk Gennady S, Gaudry Quentin, Masino Mark A, Calabrese Ronald L
Biology Department, Emory University, Atlanta, Georgia 30322, USA.
J Neurosci. 2002 Dec 15;22(24):10580-92. doi: 10.1523/JNEUROSCI.22-24-10580.2002.
Rhythmic activity within the heartbeat pattern generator of the medicinal leech is based on the alternating bursting of mutually inhibitory pairs of oscillator heart interneurons (half-center oscillators). Bicuculline methiodide has been shown to block mutual inhibition between these interneurons and to cause them to spike tonically while recorded intracellularly (Schmidt and Calabrese, 1992). Using extracellular recording techniques, we show here that oscillator and premotor heart interneurons continue to burst when pharmacologically isolated with bicuculline, although the bursting is not robust in some preparations. We propose that a nonspecific leak current introduced by the intracellular microelectrode suppresses endogenous bursting activity to account for the discrepancy with results using intracellular recording. A two-parameter bifurcation diagram (E(leak) vs g(leak)) of a mathematical model of a single heart interneuron shows a narrow stripe of parameter values where bursting occurs, separating large zones of tonic spiking and silence. A similar analysis performed for a half-center oscillator model outlined a much larger area of bursting. Bursting in the half-center oscillator model is also less sensitive to variation in the maximal conductances of voltage-gated currents than in the single-neuron model. Thus, in addition to ensuring appropriate bursting characteristics such as period, phase, and duty cycles, the half-center configuration enhances oscillation robustness, making them less susceptible to random or imposed changes in membrane parameters. Endogenous bursting, in turn, ensures appropriate bursting if the strength of mutual inhibition is weakened and limits the minimum period of the half-center oscillator to a period near that of the single neuron.
药用水蛭心跳模式发生器中的节律性活动基于相互抑制的振荡性心脏中间神经元对(半中枢振荡器)的交替爆发。已证明荷包牡丹碱甲碘化物可阻断这些中间神经元之间的相互抑制,并在细胞内记录时使它们产生强直性放电(施密特和卡拉布雷斯,1992年)。在这里,我们使用细胞外记录技术表明,当用荷包牡丹碱进行药理学隔离时,振荡性和运动前心脏中间神经元会继续爆发,尽管在某些标本中爆发并不强烈。我们提出,细胞内微电极引入的非特异性泄漏电流会抑制内源性爆发活动,以解释与细胞内记录结果的差异。单个心脏中间神经元数学模型的双参数分岔图(E(leak) 与 g(leak))显示了一个狭窄的参数值条带,在该条带处会发生爆发,将强直性放电和静息的大区域分隔开。对一个半中枢振荡器模型进行的类似分析勾勒出了一个大得多的爆发区域。与单个神经元模型相比,半中枢振荡器模型中的爆发对电压门控电流的最大电导变化也不太敏感。因此,除了确保适当的爆发特征,如周期、相位和占空比外,半中枢配置还增强了振荡的稳健性,使其更不易受到膜参数随机或强加变化的影响。反过来,如果相互抑制的强度减弱,内源性爆发会确保适当的爆发,并将半中枢振荡器的最短周期限制在接近单个神经元的周期。