Department of Biology, The University of North Carolina at Greensboro, Greensboro, USA.
Sci Rep. 2022 Jul 8;12(1):11610. doi: 10.1038/s41598-022-15525-8.
Neural networks tune synaptic and cellular properties to produce stable activity. One form of homeostatic regulation involves scaling the strength of synapses up or down in a global and multiplicative manner to oppose activity disturbances. In American bullfrogs, excitatory synapses scale up to regulate breathing motor function after inactivity in hibernation, connecting homeostatic compensation to motor behavior. In traditional models of homeostatic synaptic plasticity, inactivity is thought to increase synaptic strength via mechanisms that involve reduced Ca influx through voltage-gated channels. Therefore, we tested whether pharmacological inactivity and inhibition of voltage-gated Ca channels are sufficient to drive synaptic compensation in this system. For this, we chronically exposed ex vivo brainstem preparations containing the intact respiratory network to tetrodotoxin (TTX) to stop activity and nimodipine to block L-type Ca channels. We show that hibernation and TTX similarly increased motoneuron synaptic strength and that hibernation occluded the response to TTX. In contrast, inhibiting L-type Ca channels did not upregulate synaptic strength but disrupted the apparent multiplicative scaling of synaptic compensation typically observed in response to hibernation. Thus, inactivity drives up synaptic strength through mechanisms that do not rely on reduced L-type channel function, while Ca signaling associated with the hibernation environment independently regulates the balance of synaptic weights. Altogether, these results point to multiple feedback signals for shaping synaptic compensation that gives rise to proper network function during environmental challenges in vivo.
神经网络调节突触和细胞特性以产生稳定的活动。一种形式的自身平衡调节涉及以全局和乘法方式增强或减弱突触的强度，以对抗活动干扰。在美国牛蛙中，兴奋性突触会增强，以调节冬眠中不活动时的呼吸运动功能，将自身平衡补偿与运动行为联系起来。在传统的自身平衡突触可塑性模型中，认为不活动会通过涉及电压门控通道中 Ca 流入减少的机制来增加突触强度。因此，我们测试了在该系统中，药理学不活动和电压门控 Ca 通道抑制是否足以驱动突触补偿。为此，我们将包含完整呼吸网络的离体脑干标本在体外长时间暴露于河豚毒素 (TTX) 以停止活动，并使用尼莫地平阻断 L 型 Ca 通道。我们发现冬眠和 TTX 同样增加运动神经元突触强度，而冬眠阻断了 TTX 的反应。相比之下，抑制 L 型 Ca 通道不会上调突触强度，但会破坏通常在冬眠反应中观察到的突触补偿的明显乘法缩放。因此，不活动通过不依赖于 L 型通道功能降低的机制来增强突触强度，而与冬眠环境相关的 Ca 信号独立调节突触权重的平衡。总而言之，这些结果表明，有多种反馈信号用于塑造突触补偿，从而在体内环境挑战期间产生适当的网络功能。
