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Giant Spontaneous Depolarizing Potentials in the Developing Thalamic Reticular Nucleus

¹Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California; and ²Laboratory of Genetic Neuropharmacology, McLean Hospital, Mailman Research Center, Harvard Medical School, Belmont, Massachusetts

Submitted 20 June 2006; accepted in final form 19 January 2007

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_AR 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 3 subunit [3(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 3(H126R) mice, indicating that the GABA_ARs containing 3 are not critical for tGDP generation and suggesting that tGDPs are mediated by GABA_ARs containing the 5 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 Ca²⁺ entry and play a role in functional development of the spindle-generating circuitry.

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