Contribution of the potassium-chloride co-transporter KCC2 to the modulation of lumbar spinal networks in mice.
Spontaneous activity is observed in most developing neuronal circuits, such as the retina, hippocampus, brainstem and spinal cord. In the spinal cord, spontaneous activity is important for generating embryonic movements critical for the proper development of motor axons, muscles and synaptic connections. A spontaneous bursting activity can be recorded in vitro from ventral roots during perinatal development. The depolarizing action of the inhibitory amino acids γ-aminobutyric acid and glycine is widely proposed to contribute to spontaneous activity in several immature systems. During development, the intracellular chloride concentration decreases, leading to a shift of equilibrium potential for Cl(-) ions towards more negative values, and thereby to a change in glycine- and γ-aminobutyric acid-evoked potentials from depolarization/excitation to hyperpolarization/inhibition. The up-regulation of the outward-directed Cl(-) pump, the neuron-specific potassium-chloride co-transporter type 2 KCC2, has been shown to underlie this shift. Here, we investigated whether spontaneous and locomotor-like activities are altered in genetically modified mice that express only 8-20% of KCC2, compared with wild-type animals. We show that a reduced amount of KCC2 leads to a depolarized equilibrium potential for Cl(-) ions in lumbar motoneurons, an increased spontaneous activity and a faster locomotor-like activity. However, the left-right and flexor-extensor alternating pattern observed during fictive locomotion was not affected. We conclude that neuronal networks within the spinal cord are more excitable in KCC2 mutant mice, which suggests that KCC2 strongly modulates the excitability of spinal cord networks.
Laboratoire Plasticité et Physio-Pathologie de la Motricité (UMR 6196), CNRS & Aix-Marseille Université, Marseille, France.
Aurélie
A
Stil
Céline
C
Jean-Xavier
Sylvie
S
Liabeuf
Cécile
C
Brocard
Eric
E
Delpire
Laurent
L
Vinay
Jean-Charles
JC
Viemari
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D008159:Lumbar Vertebrae; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D013116:Spinal Cord / Q000033:anatomy & histology* / Q000502:physiology*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D002034:Bumetanide; D005665:Furosemide; D049994:Sodium Potassium Chloride Symporter Inhibitors; D027981:Symporters; D000096922:K Cl- Cotransporters