Neural circuit functions are stabilized by homeostatic processes at long timescales in response to changes in behavioral states, experience, and learning. However, it remains unclear which specific physiological variables are being stabilized and which cellular or neural network components compose the homeostatic machinery. At this point, most evidence suggests that the distribution of firing rates among neurons in a neuronal circuit is the key variable that is maintained around a set-point value in a process called ‘firing rate homeostasis.’ Here, we review recent findings that implicate mitochondria as central players in mediating firing rate homeostasis. While mitochondria are known to regulate neuronal variables such as synaptic vesicle release or intracellular calcium concentration, the mitochondrial signaling pathways that are essential for firing rate homeostasis remain largely unknown. We used basic concepts of control theory to build a framework for classifying possible components of the homeostatic machinery that stabilizes firing rate, and we particularly emphasize the potential role of sleep and wakefulness in this homeostatic process. This framework may facilitate the identification of new homeostatic pathways whose malfunctions drive instability of neural circuits in distinct brain disorders.

神经回路功能通过长时间尺度的稳态过程来稳定，以响应行为状态、经验和学习的变化。然而，目前尚不清楚哪些特定的生理变量正在稳定，哪些细胞或神经网络组件构成了稳态机制。在这一点上，大多数证据表明，神经元回路中神经元之间的放电率分布是关键变量，该变量在称为“放电率稳态”的过程中保持在设定值附近。在这里，我们回顾了最近的发现，这些发现暗示线粒体是调节放电率稳态的核心参与者。虽然已知线粒体可以调节神经元变量，例如突触小泡释放或细胞内钙浓度，对放电率稳态至关重要的线粒体信号通路在很大程度上仍然未知。我们使用控制理论的基本概念来构建一个框架，用于对稳定放电率的稳态机制的可能组成部分进行分类，并且我们特别强调了睡眠和觉醒在这个稳态过程中的潜在作用。该框架可能有助于识别新的稳态通路，这些通路的故障会导致不同脑部疾病中神经回路的不稳定。