Synaptic Activation of GABAA Receptors Inhibits AMPA/Kainate Receptor-Mediated Spontaneous Bursting in the CA3-CA1 Circuitry of the Newborn (P0-P2) Rat Hippocampus. Karri Lamsa, J. Matias Palva, Eva Ruusuvuori, Kai Kaila, and Tomi Taira. Department of Biosciences, Division of Animal Physiology, P.O.Box 17, University of Helsinki, 00014, Finland.
APStracts 6:0472N, 1999.
The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It has been reported that in the CA3-CA1 pyramidal cells a conversion of "silent" glutamatergic synapses to conductive AMPA synapses starts gradually after P2. Further, GABA via its depolarising action seems to give rise to grossly synchronous yet slow calcium oscillations, hence it is generally thought to have a purely excitatory rather than an inhibitory role during the first postnatal week. In the present study we have used field potential recordings, gramicidin perforated- and whole-cell clamp techniques, as well as K+ -selective microelectrodes to examine the relative contributions of (-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and (-aminobutyric acid-A (GABAA) receptors to network activity of CA3-CA1 pyramidal cells in the newborn rat hippocampus. We now report that already at P0-P2 highly coherent spontaneous firing of CA3 pyramidal cells is seen in vitro. Negative-going extracellular spikes confined to periodical bursts (interval 16 ( 3 s) consisting of 2.9 ( 0.1 spikes were observed in stratum pyramidale. The spikes were accompanied by AMPA-R mediated PSCs in simultaneously recorded pyramidal neurons (7.6 ( 3.0 unitary currents/burst). In CA1 pyramidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20Hz frequencies thus demonstrating the transfer of the fast CA3 network activity to CA1 area already at P0-P2. Despite its depolarising action, GABAA-R mediated transmission appeared to exert inhibition in CA3 pyramidal cell population. The GABAA-R antagonist bicuculline hypersynchronised the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, while the GABAA-R agonist muscimol (100 nM) did the opposite. However, the occurrence of unitary GABAA-R currents was increased upon muscimol application from 0.66 ( 0.16 s-1 to 1.43 ( 0.29 s-1. We conclude that AMPA synapses are critical in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission already at P0-P2 in rat hippocampus. Concurrently, while GABAA-R-mediated depolarization may excite hippocampal interneurons, in CA3 pyramidal neurons it restrains excitatory inputs and limits the size of the activated neuronal population.
Received 1 June 1999; accepted in final form 16 September 1999.
APS Manuscript Number J453-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999