Abstract
Firing rate homeostasis (FRH) stabilizes neural activity. A pervasive and intuitive theory argues that a single variable, calcium, is detected and stabilized through regulatory feedback. A prediction is that ion channel gene mutations with equivalent effects on neuronal excitability should invoke the same homeostatic response. In agreement, we demonstrate robust FRH following either elimination of Kv4/Shal protein or elimination of the Kv4/Shal conductance. However, the underlying homeostatic signaling mechanisms are distinct. Eliminating Shal protein invokes Krüppel-dependent rebalancing of ion channel gene expression including enhanced slo, Shab, and Shaker. By contrast, expression of these genes remains unchanged in animals harboring a CRISPR-engineered, Shal pore-blocking mutation where compensation is achieved by enhanced IKDR. These different homeostatic processes have distinct effects on homeostatic synaptic plasticity and animal behavior. We propose that FRH includes mechanisms of proteostatic feedback that act in parallel with activity-driven feedback, with implications for the pathophysiology of human channelopathies.
Highlights
Firing Rate Homeostasis (FRH) is a form of homeostatic control that stabilizes spike rate and information coding when neurons are confronted by pharmacological, genetic or environmental perturbation (Davis, 2013; O’Leary et al, 2014)
We first established a system to assess firing rate homeostasis following the elimination of the somatic A-type potassium channel encoded by the Shal gene, which contributes to the A-type potassium current (IKA)
To further investigate the precision of Firing rate homeostasis (FRH), we examined the effects of 4-AP and Shal knockdown on action potential waveforms
Summary
Firing Rate Homeostasis (FRH) is a form of homeostatic control that stabilizes spike rate and information coding when neurons are confronted by pharmacological, genetic or environmental perturbation (Davis, 2013; O’Leary et al, 2014). FRH has been widely documented within invertebrate neurons (Turrigiano et al, 1994; Muraro et al, 2008; Driscoll et al, 2013) and neural circuits (Haedo and Golowasch, 2006) as well as the vertebrate spinal cord (Gonzalez-Islas et al, 2010), cortical pyramidal neurons (Andrasfalvy et al, 2008) and cardiomyocytes (Guo et al, 2005; Marrus and Nerbonne, 2008; Michael et al, 2009) In many of these examples, the genetic deletion of an ion channel is used to induce a homeostatic response. Our data are consistent with the existence of separable proteostatic and activity-dependent homeostatic signaling systems, potentially acting in concert to achieve cell-type-specific and perturbation-specific FRH
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
