Division of Biological Sciences, University of Missouri-Columbia, MO, USA.
BMC Biol. 2024 Nov 4;22(1):251. doi: 10.1186/s12915-024-02050-5.
Neural circuits produce reliable activity patterns despite disturbances in the environment. For this to occur, neurons elicit synaptic plasticity during perturbations. However, recent work suggests that plasticity not only regulates circuit activity during disturbances, but these modifications may also linger to stabilize circuits during future perturbations. The implementation of such a regulation scheme for real-life environmental challenges of animals remains unclear. Amphibians provide insight into this problem in a rather extreme way, as circuits that generate breathing are inactive for several months during underwater hibernation and use compensatory plasticity to promote ventilation upon emergence.
Using ex vivo brainstem preparations and electrophysiology, we find that hibernation in American bullfrogs reduces GABA receptor (GABAR) inhibition in respiratory rhythm generating circuits and motor neurons, consistent with a compensatory response to chronic inactivity. Although GABARs are normally critical for breathing, baseline network output at warm temperatures was not affected. However, when assessed across a range of temperatures, hibernators with reduced GABAR signaling had greater activity at cooler temperatures, enhancing respiratory motor output under conditions that otherwise strongly depress breathing.
Hibernation reduces GABAR signaling to promote robust respiratory output only at cooler temperatures. Although frogs do not ventilate lungs during underwater hibernation, we suggest this would be beneficial for stabilizing breathing when the animal passes through a large temperature range during emergence in the spring. More broadly, these results demonstrate that compensatory synaptic plasticity can increase the operating range of circuits in harsh environments, thereby promoting adaptive behavior in conditions that suppress activity.
尽管环境中存在干扰，神经回路仍能产生可靠的活动模式。为了实现这一点，神经元会在受到干扰时引发突触可塑性。然而，最近的研究表明，可塑性不仅可以调节干扰期间的电路活动，而且这些修改还可能在未来的干扰中稳定电路。目前尚不清楚动物在现实环境挑战中实施这种调节方案的情况。两栖动物以一种相当极端的方式为我们提供了对这个问题的深入了解，因为在水下冬眠期间，产生呼吸的回路会有几个月处于不活跃状态，而利用代偿性可塑性来促进呼吸的恢复。
我们通过离体脑桥标本和电生理学方法发现，美洲牛蛙在冬眠期间，呼吸节律产生回路和运动神经元中的 GABA 受体（GABAR）抑制作用降低，这与对慢性不活动的代偿反应一致。尽管 GABAR 对呼吸至关重要，但在温暖温度下，基线网络输出不受影响。然而，在评估一系列温度下，GABAR 信号减少的冬眠者在较冷温度下的活动增加，在其他强烈抑制呼吸的条件下增强了呼吸运动输出。
冬眠会降低 GABAR 信号，以促进仅在较冷温度下产生强劲的呼吸输出。尽管青蛙在水下冬眠期间不会呼吸肺部，但我们认为这对于稳定呼吸是有益的，因为当动物在春季出现时，会经历较大的温度范围。更广泛地说，这些结果表明代偿性突触可塑性可以增加电路在恶劣环境中的工作范围，从而在抑制活动的条件下促进适应性行为。
