Describing the genetic development of cortical GABAergic interneurons

In this fascinating piece of work, Okaty et al recently set out to describe the various upregulations and downregulations of genes in genetically labeled, fast-spiking, parvalbumin-expressing, rodent GABAergic interneurons during the first 6 postnatal weeks. Because they restricted their genetic analysis to one subset of cells, their results are more specific than if they had conducted a transcriptome wide assay on a given tissue.

Contrary to the old dogma that maturation involves simply an increase in the total number of ion channels and an increase in excitability, their results suggest a more nuanced stance. In this new approach, subsets of certain ion channels may emerge and recede as dictated by necessity. Certain channels that are useful in development may no longer serve a purpose in mature cells (so the driving force for degradation would be energetics), or may even hinder the mature cell's function.

Specifically, of the downregulated ion channels they analyzed, seven of the thirteen subunits are associated with channels that flux calcium. For example, Cacng5 mRNA was downregulated about 89 fold. As these fast-spiking interneurons develop, their intracellular calcium concentration is liable to spiral out of control, as the increased number of action potentials will lower the average membrane potential and activate voltage-gated calcium channels much more often. So the downregulation of calcium channels could be a plausible mechanism for maintaining homeostasis in the cell. It would be interesting to study whether the mRNA downregulation is intrinsic to the cell type or if is a negative feedback mechanism triggered in response to increased intracellular calcium concentrations; one might do this by optogenetically controlling access to extracellular calcium.

The researchers also consider some synaptic properties of these interneurons. All in all, a very thoroughly researched paper that demonstrates both the complexity of the developmental genetic code and our increasing ingenuity in cracking it.

Reference

Okaty BW, et al. 2009 Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons. The Journal of Neuroscience, 29. 7040-7052; doi:10.1523/JNEUROSCI.0105-09.2009.