Variability & co-variations in ion channel expression & electrophysiological properties in neurons
Blue Brain Seminar in Neural Computation. Speaker - Jean-Marc Goaillard, Inserm CRCN, Group Leader ‘Systems Approaches to Neuronal Excitability’ group, Institut de Neurosciences de la Timone, Marseille, France.
“In spite of the considerable biophysical knowledge available about ion channel types and properties, we still have a poor understanding of how a specific neuronal type invariably achieves its characteristic electrical phenotype and maintains it in spite of all the insults the neuron faces during its long lifespan.
This lack of understanding seems to be essentially due to the fact that i) any neuronal type relies on a large number of different ion channel subtypes to generate its characteristic electrical phenotype, ii) the respective expression levels of these ion channels are critical in defining their impact, and iii), the functional impact of these ion channels is also influenced by the morphology of the neuron.
Over the past six years, we have tried to develop systems-level approaches to understand how midbrain dopaminergic neurons invariably generate a stable electrical phenotype when recorded in vitro (pacemaking activity, broad action potential, etc...). In particular, we used a combination of single-neuron transcriptomics, electrophysiological recordings, and advanced multivariate mathematical analysis to try to understand how quantitative changes in ion channel expression levels may explain variations in the electrical phenotype (or stability thereof).
As described in other systems, we found that ion channel expression levels are highly variable from neuron to neuron, even in this well-identified neuronal population. We also found that electrophysiological properties displayed significant variations from neuron to neuron. More interestingly, we found that both ion channel expression levels and specific electrophysiological properties co-varied, highlighting the presence of invariant high-dimensional relationships. We believe that these co-variations play an essential role in achieving a given electrophysiological phenotype and maintaining it over time in the face of perturbations”.
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