title: Temporal patterns and depolarizing actions of spontaneous GABAA receptor activation in granule cells of the early postnatal dentate gyrus.
abstract: Whole cell patch-clamp recordings were used to investigate the properties of the gamma-aminobutyric acid type A (GABAA) receptor-mediated spontaneous synaptic events in immature granule cells of the developing, early postnatal day (P0-P6) rat dentate gyrus. With Cs-gluconate-filled 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 frequency 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 picrotoxin as well as the intracellularly applied chloride-channel blockers CsF- and 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS) abolished the intraburst as well as the interburst IPSCs, indicating that the IPSCs were mediated by GABAA receptor channels. The bursts of IPSCs, but not the interburst IPSCs, were blocked by the simultaneous application of the glutamate receptor antagonists 2-amino-5-phosphovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, indicating the importance of the glutamatergic excitatory drive onto the interneurons in the early postnatal dentate gyrus. The spontaneously occurring excitatory postsynaptic currents in immature granule cells, observable after the intracellular blockade of GABAA receptor channels with CsF- and 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 resting membrane potential (-54.2 +/- 4.2 mV) but more hyperpolarized than the action potential threshold (-41. 8 +/- 1.7 mV). The depolarizing action 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 of immature granule cells of the developing dentate gyrus, determined that the bursts of IPSPs took place in a similar temporal pattern but with imperfect synchrony in neighboring granule cells (average lag between the onsets of the bursts between granule cell pairs 77.7 +/- 8.6 ms). These results show that the spontaneous activation of GABAA receptors in immature dentate granule cells displays unique properties that are distinct from the temporal patterns and biophysical features of spontaneous GABAA receptor activation taking place in the developing Ammon's horn and in the adult dentate gyrus.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, California 92697-1280, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Hollrigel
authors.forename: S T
authors.initials: ST
authors.lastname: Ross
authors.forename: I
authors.initials: I
authors.lastname: Soltesz
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D018891:Dentate Gyrus / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013997:Time Factors
chemical_list: D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate