Maintaining average activity level within a set-point range constitutes a fundamental property of central neural circuits. Accumulated evidence suggests that firing rate distributions and their means represent physiological variables regulated by homeostatic systems during sleep-wake cycle in central neural circuits. While intracellular Ca2+ has long been hypothesized as a feedback control signal, the source of Ca2+ and the molecular machinery enabling network-wide homeostatic responses remain largely unknown. I will present our hypothesis and framework on identifying homeostatic regulators in neural circuits. Next, I will show our new results on the role of mitochondria in the regulation of activity set-points and feedback responses. Finally, I will provide an evidence on state-dependent dysregulation of activity set-points at the presymptomatic disease stage in familial Alzheimer’s models.

During the course of an animal’s interaction with its environments, activity within central neural circuits is orchestrated exquisitely to structure goal-oriented movement. During walking, for example, the head, body and limbs are coordinated in distinctive ways that are guided by the task at play, and also by posture and balance requirements. Hence, the overall performance of goal-oriented walking depends on the interplay between task-specific motor plans and stability reflexes. Copies of motor plans, typically described by the term efference copy, modulate stability reflexes in a predictive manner. However, the highly uncertain nature of natural environments indicates that the effect of efferent copy on movement control is insufficient; additional mechanisms must exist to regulate stability reflexes and coordinate motor programs flexibly under non-predictable conditions. In this talk, I will discuss our recent work examining how self-generated visual signals orchestrate the interplay between task-specific motor plans and stability reflexes during a self-paced, goal-oriented walking behavior.