Dante Bortone and Franck Polleux are the lead authors on the paper titled “KCC2 expression promotes the termination of cortical interneuron migration in a voltage-sensitive calcium-dependent manner” that was published in Neuron.
Proper development of cortical microcircuits requires the coordinated transition between neuronal migration and synaptogenesis for both excitatory pyramidal neuronsand inhibitory interneurons. The cellular and molecuar mechanisms controlling the termination of cortical interneuron migration are currently unknown. The lab was able to demonstrate that the depolarizing effects of both GABA and glutamate stimulate the migration of immature interneurons. However, upon reaching the cortex, migrating interneurons change thier responsiveness to ambient GABA which becomes a stop signal. The lab found that this change is mediated by up-regulation of the potassium-chloride co-transporter KCC2 andits ability to decrease membrane potential upon GABA receptor activation and thereby decrease the frequency of calcium transients. The results suggest a novel mechanism whereby migrating interneurons determine the relative density of surrounding interneurons and pyramidal cells through their ability to sense the combined extracellular levels of ambient glutamate and GABA prior to synaptogenesis.