Firing rate homeostasis through the co-expression of two feedback mechanisms that detect separate aspects of neuronal activity
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Sarah Pellizzari (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Joseph Santin
Abstract: How do neurons produce consistent patterns of electrical activity throughout life? Foundational studies suggest neurons self-regulate activity through molecular feedback loops that track a single cellular variable whose dynamics mirror firing rate, such as Ca2+, Na+, or voltage over both long and short timescales. The low affinity Na+/K+ATPase, termed the dynamic Na+/K+ATPase, which tracks intracellular Na+, has emerged as an activity regulator over the span of approximately one minute by producing the ultraslow afterhyperpolarization (usAHP) in spinal locomotor circuits. In this study, we sought to investigate the role of the dynamic Na+/K+ATPase in regulating the activity of neurons that produce breathing using vagal and hypoglossal respiratory motoneurons. Here we report that vagal motoneurons have an usAHP, while hypoglossal motoneurons do not. Despite having a phenotype similar to the locomotor usAHP, the usAHP in respiratory vagal motoneurons is generated not only by the dynamic Na+/K+ATPase but also by voltage-dependent recruitment of Kv7 channels. Furthermore, both mechanisms are variably expressed across populations of neurons but have an inverse functional relationship from cell to cell (when the dynamic Na+/K+ ATPase is high, Kv7 is low and vice versa). Both the dynamic Na+/K+ATPase and Kv7 channels regulate firing rate through activity-dependent feedback during physiological bursting, with the contribution of each reciprocally balanced. These findings reveal that neurons can use various combinations of different feedback signals to defend firing rate set-points and highlight the potential for difficulty in defining global homeostatic rules even within a population of neurons that give rise to the same behavior.
Firing rate homeostasis through the co-expression of two feedback mechanisms that detect separate aspects of neuronal activity
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Created on 8/1/2022
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Additional Information
- Publication
- Thesis
- Language: English
- Date: 2022
- Keywords
- Intrinsic Excitability Regulation, Kv7 Channel, Na+/K+ATPase
- Subjects
- Motor neurons $x Physiology
- Sodium/potassium ATPase
- Potassium channels
- Homeostasis