Activity-Independent Coregulation of I_A and I_h in Rhythmically Active Neurons

Abstract

The fast transient potassium or A current (IA) plays an important role in determining the activity of central pattern generator neurons. We have previously shown that the shal K+ channel gene encodes IA in neurons of the pyloric network in the spiny lobster. To further study how IA shapes pyloric neuron and network activity, we microinjected RNA for a shal-GFP fusion protein into four identified pyloric neuron types. Neurons expressing shal-GFP had a constant increase in IA amplitude, regardless of cell type. This increase in IA was paralleled by a concomitant increase in the hyperpolarization-activated cation current Ih in all pyloric neurons. Despite significant increases in these currents, only modest changes in cell firing properties were observed. We used models to test two hypotheses to explain this failure to change firing properties. First, this may reflect the mislocalization of the expressed shal protein solely to the somata and initial neurites of injected neurons, rendering it electrically remote from the integrating region in the neuropil. To test this hypothesis, we generated a multicompartment model where increases in IA could be localized to the soma, initial neurite, or neuropil/axon compartments. Although spike activity was somewhat more sensitive to increases in neuropil/axon versus somatic/primary neurite IA, increases in IA limited to the soma and primary neurite still evoked much more dramatic changes than were seen in the shal-GFP-injected neurons. Second, the effect of the increased IA could be compensated by the endogenous increase in Ih. To test this, we modeled the compensatory increases of IA and Ih with a cycling two-cell model. We found that the increase in Ih was sufficient to compensate the effects of increased IA, provided that they increase in a constant ratio, as we observed experimentally in both shal-injected and noninjected neurons. Thus an activity-independent homeostatic mechanism maintains constant neuronal activity in the face of dramatic increases in IA.

Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression

“…We showed that although the same identified neurons in different animals display 3-to 5-fold variability in the level of expression of any one ion channel, these expression levels are not independently variable, but show cell-specific correlations. Although compensatory changes in gene expression have been demonstrated previously between shal and IH (27,28), our work reveals the potential extent to which channel genes are coregulated in neurons known to maintain constant function in the networks in which they function (29). We argue that cell identity is not a static result of gene expression, but rather a continual balance between compensatory changes in gene expression and coordinated gene regulation that ensures robust output.…”

Ca2+/cAMP-Sensitive Covariation ofIAandIHVoltage Dependences Tunes Rebound Firing in Dopaminergic Neurons

“…Consistent with this hypothesis, recent studies performed in the invertebrate nervous system have demonstrated that numerous ion channels/ currents display correlated levels of expression/amplitude in unperturbed populations of neurons (MacLean et al, 2005;Schulz et al, 2006Schulz et al, , 2007Khorkova and Golowasch, 2007;Goaillard et al, 2009;Tobin et al, 2009;Temporal et al, 2011). Moreover, some of these correlations in ion channel properties were demonstrated to be cell-type specific and strongly predict the functional output of the neuron (Schulz et al, 2007;).…”

Homeostasis of functional maps in active dendrites emerges in the absence of individual channelostasis

“…Furthermore, activity-dependent changes in synapses and in VGICs underlying some functional maps have shown to be governed by the same underlying signaling mechanisms (3,(41)(42)(43)(44)(45), imposing additional dependencies on the covariance among these functional maps. Finally, there is experimental evidence from several systems for activity-dependent and independent mechanisms of maintaining the coexpression of specific conductances (13,15,(46)(47)(48)(49)(50)(51)(52)(53). How do we reconcile these observations with the absence of strong pairwise correlations (Fig.…”