Journal of Neurophysiology, Vol 76, Issue 4 2568-2579, Copyright © 1996 by APS

ARTICLES

GABAA receptor function in developing rat thalamic reticular neurons: whole cell recordings of GABA-mediated currents and modulation by clonazepam

J. W. Gibbs 3rd, G. B. Schroder and D. A. Coulter
Department of Neurology, Medical College of Virginia, Richmond 23298-0599, USA.

1. Nucleus reticularis thalami (NRT) is a nucleus composed entirely of GABAergic neurons, which functions as a pacemaker to synchronize thalamocortical oscillations. To study the functional properties of GABAergic inhibition mediated through activation of gamma-aminobuturic acid-A (GABAA) receptors in these cells, neurons were isolated acutely from NRT at various postnatal developmental stages and recorded from using whole cell patch-clamp techniques. 2. Application of GABA to NRT neurons elicited a large, bicuculline sensitive current with an average reversal potential of -60.6 +/- 1.9 mV (mean +/- SD) in postnatal day (p) 19-21 neurons and -51.2 +/- 3.1 mV in p7 neurons, presumably mediated through activation of a GABAA-mediated chloride conductance. The potency of GABA in activating GABAA receptors decreased significantly with postnatal development in NRT neurons and was best fitted with EC50s of 24.9, 33.9, and 67.2 microM, in neurons isolated from p5-9, p18-25, and p58-74 rats, respectively. The density of GABAA receptors in the membranes of NRT neurons increased significantly with postnatal development. In addition, the GABA current decay rate slowed significantly in neurons isolated from older animals relative to early postnatal rat pups. 3. Both the potency and efficacy of benzodiazepine augmentation of GABAA responses in NRT neurons increased significantly with development. The EC50 of clonazepam decreased from 26 to 6 nM in p5-9 and p58-74 NRT neurons, respectively, whereas the efficacy increased from 126 to 163% augmentation over the same developmental range. 4. The elevated efficacy of clonazepam (CNZ) in NRT neurons relative to thalamic and cortical neurons, particularly in neurons isolated from adult (> p58) rats, is consistent with the anticonvulsant profile of this drug in controlling Generalized Absence epilepsy. Augmenting inhibition within NRT would enhance NRT/ NRT inhibitory connections and thereby decrease the amplitude of NRT-mediated synchronizing inhibitory postsynaptic potentials onto thalamus (where CNZ has low efficacy), in turn making it more difficult to elicit burst firing in thalamus due to deinactivation and subsequent activation of the low-threshold Ca2+ current. 5. The present developmental profile of GABAA responses in GABAergic NRT neurons provides data important in understanding the role of GABAergic inhibition within NRT in the modulation of normal and pathological thalamocortical rhythms in the brain and is also relevant in understanding potential differences in GABAA receptor physiology and pharmacology in GABAergic interneurons relative to glutamatergic neurons.

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