Giant spontaneous depolarizing potentials in the developing thalamic reticular nucleus.
The thalamic reticular nucleus (nRt) provides a major source of inhibition in the thalamo-cortical circuit and is critically involved in the generation of spindle oscillations. Here we describe the properties of thalamic giant depolarizing potentials (tGDPs) that were observed in nRt during early development. tGDPs persisted in presence of ionotropic glutamate antagonists but were completely abolished by GABA(A)R antagonist SR 35591. tGDPs occurred primarily between p3 and p8 (in 30-50% of cells) and occasionally up until p15. tGDPs lasted 0.4-3 s with peak conductances of 2-13 nS and occurred at frequencies between 0.02 and 0.06 Hz. We used mice with a benzodiazepine-insensitive alpha3 subunit [alpha3(H126R)] to probe for the identity of the GABA receptors responsible for tGDP generation. Benzodiazepine enhancement of tGDP amplitude and duration persisted in nRt neurons in alpha3(H126R) mice, indicating that the GABA(A)Rs containing alpha3 are not critical for tGDP generation and suggesting that tGDPs are mediated by GABA(A)Rs containing the alpha5 subunit, which is transiently expressed in nRt neurons in early postnatal development. Furthermore we found that exogenous GABA application depolarized nRt neurons younger than p8, indicating elevated [Cl(-)](i) at this developmental stage. Taken together, these data suggest that in immature nRt, long-lasting depolarizing responses mediated by GABA receptors could trigger Ca(2+) entry and play a role in functional development of the spindle-generating circuitry.
Pangratz-Fuehrer
Susanne
S
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Rudolph
Uwe
U
Huguenard
John R
JR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002712:Chlorides / Q000378:metabolism; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011963:Receptors, GABA-A / Q000235:genetics; D013787:Thalamic Nuclei / Q000166:cytology / Q000502:physiology*
D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; C546258:Gabra3 protein, mouse; D011963:Receptors, GABA-A