Ionic current correlations are ubiquitous across phyla

Abstract

Ionic currents, whether measured as conductance amplitude or as ion channel transcript numbers, can vary many-fold within a population of identified neurons. In invertebrate neuronal types multiple currents can be seen to vary while at the same time their magnitudes are correlated. These conductance amplitude correlations are thought to reflect a tight homeostasis of cellular excitability that enhances the robustness and stability of neuronal activity over long stretches of time. Although such ionic conductance correlations are well documented in invertebrates, they have not been reported in vertebrates. Here we demonstrate with two examples, identified mouse hippocampal granule cells (GCs) and cholinergic basal forebrain neurons, that the correlation of ionic conductance amplitudes between different ionic currents also exists in vertebrates, and we argue that it is a ubiquitous phenomenon expressed by many species across phyla. We further demonstrate that in dentate gyrus GCs these conductance correlations are likely regulated in a circadian manner. This is reminiscent of the known conductance regulation by neuromodulators in crustaceans. However, in GCs we observe a more nuanced regulation, where for some conductance pairs the correlations are completely eliminated while for others the correlation is quantitatively modified but not obliterated.

Temperature compensation in a small rhythmic circuit

“…Temperature is not the only perturbation that crabs and lobsters experience. As with temperature, the responses of the STG to changes in pH are diverse across individuals ( Haley et al, 2018 ), again consistent with the large amount of animal-to-animal variability in the expression of ion channels ( Schulz et al, 2006 ; Temporal et al, 2014 ; Tran et al, 2019 ). It is therefore reasonable to assume that the responses to a global perturbation are diverse across individuals because different compositions of channel densities—which produce similar pyloric rhythms—are differentially resilient to any given perturbation.…”

Rapid adaptation to elevated extracellular potassium in the pyloric circuit of the crab, Cancer borealis

“…Variability in neuronal conductances underlying similar activity patterns has also been demonstrated across phyla (Swensen and Bean, 2005;Nelson and Turrigiano, 2008;Tran et al, 2019). In addition, computational modeling of the pyloric network revealed that multiple combinations of independent circuit parameters can give rise to functionally identical activity patterns (Goldman et al, 2001;.…”

Reciprocally Inhibitory Circuits Operating With Distinct Mechanisms Are Differently Robust to Perturbation and Modulation

“…Model half-center circuits are typically built with two identical neurons, although experimental data suggest that the conductance values and intrinsic properties of neurons even of the same type can differ significantly (Doloc-Mihu and Calabrese, 2014; Goldman et al, 2001; Marder and Goaillard, 2006; Prinz et al, 2003; Prinz et al, 2004; Roffman et al, 2012; Schulz et al, 2006; Schulz et al, 2007; Srikanth and Narayanan, 2015; Swensen and Bean, 2005; Temporal et al, 2012; Tobin et al, 2009; Tran et al, 2019). The studies in which the dynamic clamp is used to create half-center circuits from biological neurons profit from natural cell-to-cell and animal-to-animal variability to investigate circuit responses to stressors and modulators.…”