Experimentally derived model for the locomotor pattern generator in the Xenopus embryo
Experimentally derived model for the locomotor pattern generator in the Xenopus embryo
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DOI：
10.1113/jphysiol.1995.sp021067
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发表时间：
1995-12-01
影响因子：
5.5
通讯作者：
Dale, N
中科院分区：
文献类型：
--
作者：
Dale, N
1.用Hodgkin-Huxley模型模拟非洲爪哇胚胎脊髓神经元的电压依赖性Na~+、Ca~(2+)、慢K~+和快K~+电流以及Na~+依赖性K~+电流。描述这些电流的激活、失活和松弛的参数来自于先前对非洲爪哇胚胎脊髓神经元的电压钳研究。每一股洋流都以现实的密度存在。模型神经元对电流注入的反应是重复放电。Ca~(2+)电流是响应电流注入的重复放电所必需的。快K+电流主要控制棘波宽度，而慢K+电流对神经元的重复放电特性影响较大，对棘波宽度无明显影响。如果在模型中加入锐尖微电极的分流效应，在活体细胞内记录期间，模型神经元的特性可以与先前报道的非洲爪哇胚胎神经元的特性更一致。这些模型神经元随后被用来创建一个简化版本的脊髓网络，该网络控制青蛙胚胎中的游泳。这个模型网络可以产生游泳的运动模式：左右两侧的活动交替，周期从50到120ms不等。这与在真实胚胎中观察到的周期范围非常相似。再次考虑了微电极的分流效应。K+电流的减少扰乱了运动模式，并产生了三种形式的异常运动活动，与以前在将K+通道阻滞剂应用于真实胚胎时看到的非常相似。在模型中产生正确的游泳运动模式的能力取决于K+电流和内向Na+和Ca2+电流之间的平衡，而不是它们的绝对值。该模型网络可以在非常宽的兴奋性(2-10 ns)和抑制性(2-400 ns)突触强度范围内产生一种游泳运动模式。对真实回路中生理突触强度的粗略估计(抑制约20-60 ns，兴奋约2-5 ns)落在模拟模型中游泳运动模式的突触强度范围内。无论是兴奋性突触的加强，还是抑制性突触的减弱，模型中运动活动的周期都缩短。在真实胚胎中，通过使用低水平的士的宁以分级的方式减少甘氨酸能相互抑制，已经验证了周期中期抑制的强度决定周期的预测。随着抑制的减少，假想游泳在胚胎中的周期缩短了非常接近模型预测的量。这个新的实验衍生模型可以复制真实胚胎中假想游泳的许多已知特征，并可能作为一种分析工具，试图了解非洲爪哇胚胎和相关的两栖动物胚胎的脊髓回路如何控制各种运动行为。
1. Simulations of Xenopus embryo spinal neurons were endowed with Hodgkin-Huxley-style models of voltage-dependent Na+, Ca2+, slow K+ and fast K+ currents together with a Na+-dependent K+ current. The parameters describing the activation, inactivation and relaxation of these currents were derived from previous voltage-clamp studies of Xenopus embryo spinal neurons. Each of the currents was present at realistic densities.2. The model neurons fired repetitively in response to current injection. The Ca2+ current was essential for repetitive firing in response to current injection. The fast K+ current appeared mainly to control spike width, whereas the slow K+ current exerted a powerful influence on the repetitive firing properties of the neurons without markedly affecting spike width.3. The properties of the model neurons could be made more consistent with those previously reported for Xenopus embryo neurons during intracellular recordings in vivo, if the shunting effect of the sharp microelectrode was incorporated into the model.4. The model neurons were then used to create a simplified version of the spinal network that controls swimming in the frog embryo. This model network could generate the motor pattern for swimming: the activity between the left and right sides alternated with a cycle period that varied from 50 to 120 ms. This is very similar to the range of cycle periods observed in the real embryo. The shunting effect of the microelectrode was once again taken into account.5. Reductions of the K+ currents perturbed the motor pattern and gave three forms of aberrant motor activity very similar to those previously seen during the application of K+ channel blockers to the real embryo. The ability to generate the correct motor pattern for swimming in the model depended on the balance between the K+ currents and the inward Na+ and Ca2+ currents rather than their absolute values.6. The model network could generate a motor pattern for swimming over a very wide range of excitatory (2-10 nS) and inhibitory (2-400 nS) synaptic strengths. Rough estimates of the physiological synaptic strengths in the real circuit (around 20-60 nS for inhibition and 2-5 nS for excitation) fall within the range of synaptic strengths that gave simulation of the swimming motor pattern in the model.7. The cycle period of the motor activity in the model shortened either as the excitatory synapses were strengthened or as the inhibitory synapses were weakened.8. The prediction that the strength of the mid-cycle inhibition determines cycle period has been tested by using low levels of strychnine to reduce glycinergic reciprocal inhibition in a graded manner in the real embryo. As the inhibition was reduced, the cycle period of fictive swimming in the embryo shortened by amounts very close to those predicted by the model.9. This new experimentally derived model can replicate many of the known features of fictive swimming in the real embryo and may be of value as an analytical tool in attempting to understand how the spinal circuitry of the Xenopus embryo and related amphibian embryos control a variety of motor behaviours.