Rapid developmental maturation of neocortical FS cell intrinsic excitability.
Fast-spiking (FS) cells are a prominent subtype of neocortical γ-aminobutyric acidergic interneurons that mediate feed-forward inhibition and the temporal sculpting of information transfer in neural circuits, maintain excitation/inhibition balance, and contribute to network oscillations. FS cell dysfunction may be involved in the pathogenesis of disorders such as epilepsy, autism, and schizophrenia. Mature FS cells exhibit coordinated molecular and cellular specializations that facilitate rapid responsiveness, including brief spikes and sustained high-frequency discharge. We show that these features appear during the second and third postnatal weeks driven by upregulation of K(+) channel subunits of the Kv3 subfamily. The low membrane resistance and fast time constant characteristic of FS cells also appears during this time, driven by expression of a K(+) leak current mediated by K(ir)2 subfamily inward rectifier K(+) channels and TASK subfamily 2-pore K(+) channels. Blockade of this leak produces dramatic depolarization of FS cells suggesting the possibility for potent neuromodulation. Finally, the frequency of FS cell membrane potential oscillations increases during development and is markedly slower in TASK-1/3 knockout mice, suggesting that TASK channels regulate FS cell rhythmogenesis. Our findings imply that some of the effects of acidosis and/or anesthetics on brain function may be due to blockade of TASK channels in FS cells.
Goldberg
Ethan M
EM
Department of Pediatrics, Division of Neurology, The Children's Hospital of Philadelphia, Abramson Research Center, Philadelphia, PA, 19104.
Jeong
Hyo-Young
HY
Kruglikov
Ilya
I
Tremblay
Robin
R
Lazarenko
Roman M
RM
Rudy
Bernardo
B
D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3