Specific brainstem neurons switch each other into pacemaker mode to drive movement by activating NMDA receptors.
Specific brainstem neurons switch each other into pacemaker mode to drive movement by activating NMDA receptors.
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DOI：
10.1523/jneurosci.3695-10.2010
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发表时间：
2010-12-08
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影响因子：
--
通讯作者：
Soffe SR
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文献类型：
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作者：
Li WC;Roberts A;Soffe SR
有节奏的活动是大脑功能的核心。在脊椎动物中枢神经系统中，呼吸和运动的神经元回路涉及抑制，也涉及起起搏器作用的神经元，但识别负责的神经元已被证明是困难的。通过研究简单的刚孵化的非洲爪蟾蝌蚪，我们已经确定了一群驱动游泳的电耦合后脑神经元（dIN）。在节律产生期间，dIN释放谷氨酸以相互兴奋并激活NMDA受体（NMDAR）。由此产生的去极化使网络机制的游泳节奏的产生，这取决于相互抑制之间的对立的右侧和左侧。令人惊讶的是，手术分离的半中枢神经系统在没有抑制的情况下仍然可以产生类似游泳的节律。我们现在已经发现，NMDAR的激活将通常单独激发电流注入的dIN转换为在正常游泳频率范围（10-25 Hz）内激发的起搏器。当dIN放电被阻断后，这种NMDAR激活产生10 Hz的膜电位振荡，当电耦合被阻断时，这种振荡持续存在，但当Mg 2+对NMDAR的电压依赖性门控被去除时，这种振荡就不存在了。NMDA诱导的振荡和起搏器发射在游泳频率是唯一的dIN人口，不发生在其他脊髓神经元。我们的结论是，NMDAR介导的自我重置开关的关键神经元，驱动游泳到起搏器模式，只有在运动过程中，它提供了一个额外的，并行的机制，节奏的产生。这允许在半个CNS中产生节律，并提高了这种隐藏的起搏器特性可能存在于其他脊椎动物脑网络中的潜在节律产生的可能性。
Rhythmic activity is central to brain function. In the vertebrate central nervous system, the neuronal circuits for breathing and locomotion involve inhibition and also neurons acting as pacemakers, but identifying the neurons responsible has proven difficult. By studying simple hatchling Xenopus laevis tadpoles, we have already identified a population of electrically coupled hindbrain neurons (dINs) which drive swimming. During rhythm generation dINs release glutamate to excite each other and activate NMDA receptors (NMDARs). The resulting depolarization enables a network mechanism for swimming rhythm generation which depends on reciprocal inhibition between antagonistic right and left sides. Surprisingly, a surgically isolated hemi-CNS without inhibition can still generate swimming-like rhythms. We have now discovered that activation of NMDARs transforms dINs, which normally fire singly to current injection, into pacemakers firing within the normal swimming frequency range (10-25 Hz). When dIN firing is blocked pharmacologically, this NMDAR activation produces 10 Hz membrane potential oscillations which persist when electrical coupling is blocked but not when the voltage-dependent gating of NMDARs by Mg2+ is removed. The NMDA-induced oscillations and pacemaker firing at swimming frequency are unique to the dIN population and do not occur in other spinal neurons. We conclude that NMDAR-mediated self-resetting switches critical neurons which drive swimming into pacemaker mode only during locomotion where it provides an additional, parallel mechanism for rhythm generation. This allows rhythm generation in a half CNS and raises the possibility that such concealed pacemaker properties may be present underlying rhythm generation in other vertebrate brain networks.