Postnatal development of GABAA receptor function in somatosensory thalamus and cortex: whole-cell voltage-clamp recordings in acutely isolated XXXX neurons.

@entity1246 @entity12988 @entity30236 @entity1245 @entity2865 @entity35 @entity2053
GABAergic inhibition synchronizes oscillatory activity in the thalamocortical system. To understand better the role of this neurotransmitter in generation of thalamocortical rhythmicity, the postnatal development of GABAergic function mediated through activation of GABAA receptors was studied in thalamus and cortex. @entity1246 -evoked @entity2865 currents were recorded in dissociated @entity35 cortical and thalamic neurons during postnatal development. Kinetic fits of @entity1246 concentration/response relationships revealed developmental and regional alterations in the potency of @entity1246 . Early in postnatal development (p5-p8), both thalamic and cortical neurons exhibited reduced potency of @entity1246 (27-31 microM KD). Potency increased by @entity12988 - @entity30236 in thalamic and cortical neurons (19-22 microM KD), to a level maintained in adult thalamic neurons. Adult cortical neurons exhibited reduced potency of @entity1246 (40 microM KD). @entity1245 modulation of GABAA currents was also studied. Kinetic analyses of @entity1245 augmentation of GABAA currents were best fitted assuming two effective sites with different affinities for @entity2053 . The high-affinity site (KD of 0.05-0.27 nM) showed little variation with development in cortical neurons, contributing about 16-23% potentiation at all postnatal ages. Developing thalamic neurons (p5- @entity30236 ) showed similar potency and efficacy of the high-affinity @entity1245 site to cortical neurons. High-affinity @entity1245 effects disappeared in adult thalamic neurons. A lower-affinity @entity1245 site (25-50 nM KD) was greater in efficacy in cortical neurons compared to thalamic neurons at all ages, with efficacy ranging from 50% to 110% in cortex and from 20% to 60% in thalamus. Knowledge of developmental and regional alterations in GABAA receptor function may aid in understanding mechanisms involved in generation and control of normal and pathological thalamocortical rhythms.
