TEMPORAL PATTERNS AND DEPOLARIZING ACTIONS OF SPONTANEOUS GABA(A) RECEPTOR ACTIVATION IN GRANULE CELLS OF THE EARLY POSTNATAL DENTATE GYRUS

Whole cell patch-clamp recordings were used to investigate the propert ies of the gamma-aminobutyric acid type A (GABA(A)) receptor-mediated spontaneous synaptic events in immature granule cells of the developin g, early postnatal day (P0-P6) rat dentate gyrus. With Cs-gluconate-fi lled whole cell patch pipettes at 0 mV in control medium, spontaneous inhibitory postsynaptic currents (sIPSCs) occurred in prominent bursts (peak amplitude of the bursts 406.9 +/- 58.4 pA; intraburst IPSC freq uency 71.0 +/- 12.4 Hz) at 0.05 +/- 0.02 Hz in every immature granule cell younger than P7. Between the bursts of IPSCs, lower frequency (1. 7 +/- 0.7 Hz), interburst IPSCs could be observed. Bicuculline and pic rotoxin as well as the intracellularly applied chloride-channel blocke rs CsF- and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) abolished the intraburst as well as the interburst IPSCs, indicating t hat the IPSCs were mediated by GABA(A) receptor channels. The bursts o f IPSCs, but not the interburst IPSCs, were blocked by the simultaneou s application of the glutamate receptor antagonists 2-amino-5-phosphov aleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, indicating the i mportance of the glutamatergic excitatory drive onto the interneurons in the early postnatal dentate gyrus. The spontaneously occurring exci tatory postsynaptic currents in immature granule cells, observable aft er the intracellular blockade of GABA(A) receptor channels with CsF- a nd DIDS, appeared exclusively as single events at low frequencies, i.e ., they did not occur in prominent bursts. Gramicidin-based perforated patch-clamp recordings determined that the reversal potential for the burst of IPSCs (-46.6 +/- 3.1 mV) was more depolarized than the resti ng membrane potential (-54.2 +/- 4.2 mV) but more hyperpolarized than the action potential threshold (-41.8 +/- 1.7 mV). The depolarizing ac tion of the bursts of synaptic events most often evoked only a single action potential per burst. Simultaneous whole cell patch recordings, with KCl-filled patch pipettes at -60 mV in current clamp from pairs o f immature granule cells of the developing dentate gyrus, determined t hat the bursts of IPSPs took place in a similar temporal pattern but w ith imperfect synchrony in neighboring granule cells (average lag betw een the onsets of the bursts between granule cell pairs 77.7 +/- 8.6 m s). These results show that the spontaneous activation of GABA, recept ors in immature dentate granule cells displays unique properties that are distinct from the temporal patterns and biophysical features of sp ontaneous GABA(A) receptor activation taking place in the developing A mmon's horn and in the adult dentate gyrus.