Neuroscience Institute, Georgia State University, Atlanta, Georgia.
Department of Biology, University of Massachusetts Amherst, Amherst, Massachusetts.
J Neurophysiol. 2022 Apr 1;127(4):1054-1066. doi: 10.1152/jn.00017.2022. Epub 2022 Mar 23.
Reciprocally inhibitory modules that form half-center oscillators require mechanisms for escaping or being released from inhibition. The central pattern generator underlying swimming by the nudibranch mollusc, , is composed of only four neurons that are organized into two competing modules of a half-center oscillator. In this system, bursting activity in left-right alternation is an emergent property of the network as a whole; none of the neurons produces bursts on its own. We found that the unique synaptic actions and membrane properties of the two neurons in each module (Si2 and the contralateral Si3) play complementary roles in generating stable bursting in this network oscillator. Although Si2 and Si3 each inhibits its contralateral counterpart, Si2 plays a dominant role in evoking fast and strong inhibition of the other module, the termination of which initiates postinhibitory rebound in the Si3 of that module by activating a hyperpolarization-activated inward current. Within each module, the synaptic actions and membrane properties of the two neurons complement each other: Si3 excites Si2, which then feeds back slow inhibition to Si3, terminating the burst. Using dynamic clamp, we showed that the magnitude of the slow inhibition sets the period of the oscillator. Thus, the synaptic actions of Si2 provide the hyperpolarization needed for the other module to rebound stably, whereas the membrane properties of Si3 in each module cause it to rebound first and excite Si2 to maintain the burst until terminated by the slow inhibition from Si2, which releases the other module to become active. Half-center oscillators composed of reciprocally inhibitory neurons have been posited for over a century to underlie the production of rhythmic movements. The swim central pattern generator may be the simplest such circuit with only two pairs of bilaterally represented neurons. This study completes the description of the mechanism by which this network oscillator functions, showing how stable rhythmic activity arises from the complementary membrane and synaptic properties of the two neurons in the competing modules.
形成半中心振荡器的相互抑制模块需要具有逃避或解除抑制的机制。 裸鳃类软体动物游泳的中枢模式发生器仅由四个神经元组成，这些神经元组织成两个竞争的半中心振荡器模块。 在该系统中，左右交替的爆发活动是整个网络的一个突现属性；没有一个神经元可以单独产生爆发。 我们发现，每个模块（Si2 和对侧 Si3）中的两个神经元的独特突触作用和膜特性在生成该网络振荡器的稳定爆发中起着互补的作用。 尽管 Si2 和 Si3 都抑制其对侧对应物，但 Si2 在引发另一个模块的快速和强烈抑制中起主导作用，其终止通过激活超极化激活内向电流来引发该模块的 Si3 中的后抑制反弹。 在每个模块中，两个神经元的突触作用和膜特性相互补充：Si3 兴奋 Si2，然后将缓慢抑制反馈给 Si3，从而终止爆发。 使用动态钳位，我们表明缓慢抑制的幅度设定了振荡器的周期。 因此，Si2 的突触作用提供了另一个模块稳定反弹所需的超极化，而每个模块中的 Si3 的膜特性使其首先反弹并兴奋 Si2，从而维持爆发，直到 Si2 的缓慢抑制终止，从而释放另一个模块使其活跃。 相互抑制神经元组成的半中心振荡器一个多世纪以来一直被认为是产生节律运动的基础。 游泳的中枢模式发生器可能是最简单的此类电路，只有两对双侧代表神经元。 本研究完成了该网络振荡器功能的机制描述，展示了竞争模块中两个神经元的互补膜和突触特性如何产生稳定的节律活动。
