GABAergic inhibition suppresses paroxysmal network activity in the neonatal rodent hippocampus and neocortex

In the adult cerebral cortex, the neurotransmitter GABA is strongly inhibit ory, as it profoundly decreases neuronal excitability and suppresses the ne twork propensity for synchronous activity. When fast, GABA(A) receptor (GAB A(A)R)-mediated neurotransmission is blocked in the mature cortex, neuronal firing is synchronized via recurrent excitatory (glutamatergic) synaptic c onnections, generating population discharges manifested extracellularly as spontaneous paroxysmal field potentials (sPFPs). This epileptogenic effect of GABA(A)R antagonists has rarely been observed in the neonatal cortex, an d indeed, GABA in the neonate has been proposed to have an excitatory, rath er than inhibitory, action. In contrast, we show here that when fast GABAer gic neurotransmission was blocked in slices of neonatal mouse and rat hippo campus and neocortex, sPFPs occurred in nearly half the slices from postnat al day 4 (P4) to P7 neocortex and in most slices from P2 to P7 hippocampus. In Mg2+-free solution, GABA(A)R antagonists elicited sPFPs in nearly all s lices of P2 and older neocortex and P0 and older hippocampus. Mg2+-free sol ution alone induced spontaneous events in the majority of P2 and older slic es from both regions; addition of GABA(A)R antagonists caused a dramatic in crease in the mean amplitude, but not frequency, of these events in the hip pocampus and in their mean frequency, but not amplitude, in the neocortex. In the hippocampus, GABA(A)R agonists suppressed amplitudes, but not freque ncy, of sPFPs, whereas glutamate antagonists suppressed frequency but not a mplitudes. We conclude that neonatal rodent cerebral cortex possesses gluta matergic circuits capable of generating synchronous network activity and th at, as in the adult, tonic GABA(A)R-mediated inhibition prevents this activ ity from becoming paroxysmal.