NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain

From an early postnatal period and throughout life there is a continuous production of olfactory bulb (OB) interneurons originating from neuronal precursors in the subventricular zone. To reach the OB circuits, immature neuroblasts migrate along the rostral migratory stream (RMS). In the present study, we employed cultured postnatal mouse forebrain slices and used lentiviral vectors to label neuronal precursors with GFP and to manipulate the expression levels of the Na-K-2Cl cotransporter NKCC1. We investigated the role of this Cl- transporter in different stages of postnatal neurogenesis, including neuroblast migration and integration in the OB networks once they have reached the granule cell layer (GCL). We report that NKCC1 activity is necessary for maintaining normal migratory speed. Both pharmacological and genetic manipulations revealed that NKCC1 maintains high [Cl-]i and regulates the resting membrane potential of migratory neuroblasts whilst its functional expression is strongly reduced at the time cells reach the GCL. As in other developing systems, NKCC1 shapes GABAA-dependent signaling in the RMS neuroblasts. Also, we show that NKCC1 controls the migration of neuroblasts in the RMS. The present study indeed indicates that the latter effect results from a novel action of NKCC1 on the resting membrane potential, which is independent of GABAA-dependent signaling. All in all, our findings show that early stages of the postnatal recruitment of OB interneurons rely on precise, orchestrated mechanisms that depend on multiple actions of NKCC1

Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin

The involvement of intracellular calcium and calmodulin in the modulation of plateau potentials in motoneurones was investigated using intracellular recordings from a spinal cord slice preparation.Chelation of intracellular calcium with BAPTA-AM or inactivation of calmodulin with W-7 or trifluoperazine reduced the amplitude of depolarization-induced plateau potentials. Inactivation of calmodulin also inhibited facilitation of plateau potentials by activation of group I metabotropic glutamate receptors or muscarinic receptors.In low-sodium medium and in the presence of tetraethylammonium and tetrodotoxin, calcium action potentials evoked by depolarization were followed by a short hyperpolarization ascribed to the calcium-activated non-selective cationic current (ICAN) and by a dihydropyridine-sensitive afterdepolarization. The amplitude of the afterdepolarization depended on the number of calcium spikes and was mediated by L-type calcium channels.The dihydropyridine-sensitive afterdepolarization induced by calcium spikes was reduced by blockade of calmodulin.It is proposed that plateau potentials in spinal motoneurones are facilitated by activation of a calcium-calmodulin-dependent pathway

Axonal speeding: shaping synaptic potentials in small neurons by the axonal membrane compartment.

International audienceThe role of the axonal membrane compartment in synaptic integration is usually neglected. We show here that in interneurons of the cerebellar molecular layer, where dendrites are so short that the somatodendritic domain can be considered isopotential, the axonal membrane contributes a significant part of the cell input capacitance. We examine the impact of axonal membrane on synaptic integration by cutting the axon with two-photon illumination. We find that the axonal compartment acts as a sink for signals generated at fast conductance synapses, thus increasing the initial decay rate of corresponding synaptic potentials over the value predicted from the resistance-capacitance (RC) product of the cell membrane; signals generated at slower synapses are much less affected. This mechanism sharpens the spike firing precision of fast glutamatergic inputs without resorting to multisynaptic pathways