Distinct strategies regulate correlated ion channel mRNAs and ionic currents in continually vs episodically active neurons.

Abstract

Relationships among membrane currents allow central pattern generator (CPG) neurons to reliably drive motor programs. We hypothesize that continually active CPG neurons utilize activity-dependent feedback to correlate expression of ion channel genes to balance essential membrane currents. However, episodically activated neurons experience absences of activity-dependent feedback, and thus, presumably employ other strategies to coregulate the balance of ionic currents necessary to generate appropriate output after periods of quiescence. To investigate this, we compared continually active pyloric dilator (PD) neurons with episodically active lateral gastric (LG) CPG neurons of the stomatogastric ganglion (STG) in male Cancer borealis crabs. After experimentally activating LG for 8 hours, we measured 3 potassium currents and abundances of their corresponding mRNAs. We found that ionic current relationships were correlated in LG’s silent state, but ion channel mRNA relationships were correlated in the active state. In continuously active PD neurons, ion channel mRNAs and ionic currents are simultaneously correlated. Therefore, two distinct relationships exist between channel mRNA abundance and the ionic current encoded in these cells: in PD, there is a direct correlation between Shal channel mRNA levels and the A-type potassium current it carries. Conversely, such channel mRNA-current relationships are not detected and appear to be temporally uncoupled in LG neurons. Our results suggest that ongoing feedback maintains membrane current and channel mRNA relationships in continually active PD neurons, while in LG neurons, episodic activity serves to establish channel mRNA relationships necessary to produce the ionic current profile necessary for the next bout of activity.

Significance statement Motor neurons must coregulate their ionic currents to ensure output stability. In neurons that are continually active, one possible strategy to achieve this involves using activity-dependent feedback to consistently maintain correlated levels of ion channel mRNAs underlying correlations among the corresponding ionic currents. However, neurons with transient periods of activity must use other strategies. We show that in episodically active neurons, ion channel mRNAs and the corresponding ionic currents are correlated in different states of activity. We propose that the temporal uncoupling between correlated mRNAs and currents in these cells allows episodically active neurons to stabilize the appropriate coregulated ionic currents even during periods of inactivity.