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The Journal of Neuroscience, December 1, 2000, 20(23):8822-8830

GABAergic Inhibition Suppresses Paroxysmal Network Activity in the Neonatal Rodent Hippocampus and Neocortex

Jason E. Wells^{1, 2}, James T. Porter¹, and Ariel Agmon^{1, 3}

¹ Department of Anatomy, the ² Neuroscience Graduate Program, and the ³ Sensory Neuroscience Research Center, West Virginia University, Morgantown, West Virginia 26506-9128

In the adult cerebral cortex, the neurotransmitter GABA is strongly inhibitory, as it profoundly decreases neuronal excitability and suppresses the network propensity for synchronous activity. When fast, GABA_A receptor (GABA_AR)-mediated neurotransmission is blocked in the mature cortex, neuronal firing is synchronized via recurrent excitatory (glutamatergic) synaptic connections, generating population discharges manifested extracellularly as spontaneous paroxysmal field potentials (sPFPs). This epileptogenic effect of GABA_AR antagonists has rarely been observed in the neonatal cortex, and indeed, GABA in the neonate has been proposed to have an excitatory, rather than inhibitory, action. In contrast, we show here that when fast GABAergic neurotransmission was blocked in slices of neonatal mouse and rat hippocampus and neocortex, sPFPs occurred in nearly half the slices from postnatal day 4 (P4) to P7 neocortex and in most slices from P2 to P7 hippocampus. In Mg²⁺-free solution, GABA_AR antagonists elicited sPFPs in nearly all slices of P2 and older neocortex and P0 and older hippocampus. Mg²⁺-free solution alone induced spontaneous events in the majority of P2 and older slices from both regions; addition of GABA_AR antagonists caused a dramatic increase in the mean amplitude, but not frequency, of these events in the hippocampus and in their mean frequency, but not amplitude, in the neocortex. In the hippocampus, GABA_AR agonists suppressed amplitudes, but not frequency, of sPFPs, whereas glutamate antagonists suppressed frequency but not amplitudes. We conclude that neonatal rodent cerebral cortex possesses glutamatergic circuits capable of generating synchronous network activity and that, as in the adult, tonic GABA_AR-mediated inhibition prevents this activity from becoming paroxysmal.

Key words: paroxysmal field potentials; GABA_A receptors; NMDA receptors; AMPA receptors; synaptic development; rodent; neocortex; hippocampus; CA3; synaptic inhibition

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20238822-09$05.00/0

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