Synaptic GABA(A) activation inhibits AMPA-kainate receptor-mediated bursting in the newborn (P0-P2) rat hippocampus

The mechanisms of synaptic transmission in the rat hippocampus at birth are assumed to be fundamentally different from those found in the adult. It ha s been reported that in the CA3-CA1 pyramidal cells a conversion of "silent " glutamatergic synapses to conductive alpha-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid (AMPA) synapses starts gradually after P2. Further. GA BA via its depolarizing action seems to give rise to grossly synchronous ye t slow calcium oscillations. Therefore, GABA is generally thought to have a purely excitatory rather than an inhibitory role during the first postnata l week. In the present study field potential recordings and gramicidin perf orated and whole cell clamp techniques as well as K+-selective microelectro des were used to examine the relative contributions of AMPA and GABA, recep tors to network activity of CA3-CA1 pyramidal cells in the newborn rat hipp ocampus. As early as postnatal day (P0-P2), highly coherent spontaneous fir ing of CA3 pyramidal cells was seen in vitro. Negative-going extracellular spikes confined to periodic bursts (interval 16 +/- 3 s) consisting of 2.9 +/- 0.1 spikes were observed in stratum pyramidale. The spikes were accompa nied by AMPA-R-mediated postsynaptic currents (PSCs) in simultaneously reco rded pyramidal neurons (7.6 +/- 3.0 unitary currents per burst). In CAI pyr amidal cells synchronous discharging of CA3 circuitry produced a barrage of AMPA currents at >20 Hz frequencies, thus demonstrating a transfer of the fast CA3 network activity to CA1 area. Despite its depolarizing action, GAB A(A)-R-mediated transmission appeared to exert inhibition in the CA3 pyrami dal cell population. The GABA(A)-R antagonist bicuculline hypersynchronized the output of glutamatergic CA3 circuitry and increased the network-driven excitatory input to the pyramidal neurons, whereas the GABA(A)-R agonist m uscimol (100 nM) did the opposite. However, the occurrence of unitary GABA( A)-R currents was increased after muscimol application from 0.66 +/- 0.16 s (-1) to 1.43 +/- 0.29 s(-1). It was concluded that AMPA synapses are critic al in the generation of spontaneous high-frequency bursts in CA3 as well as in CA3-CA1 transmission as early as P0-P2 in rat hippocampus. Concurrently , although GABA(A)-R-mediated depolarization may excite hippocampal interne urons, in CA3 pyramidal neurons it can restrain excitatory inputs and limit the size of the activated neuronal population.