Pharmacological Profile of Early Sharp Waves in the Neonatal Rat Hippocampus

Early activity patterns support the development of neuronal networks by promoting synaptic plasticity. In the hippocampus of neonatal rats and mice in vivo, early sharp waves (eSPWs) are the first pattern of synchronized network activity. The activation of glutamate- and GABA(A)-mediated synaptic currents was described during eSPWs. However, the contribution of different receptor subtypes to eSPW generation is still obscure. To explore the receptor mechanisms of eSPW generation we used a «superfused hippocampus» preparation, which allows a drug application directly to the large area of the hippocampal surface in vivo. Using silicon probe recordings from the superfused hippocampus of neonatal Wistar rats, we assessed electrophysiological properties of eSPWs in control conditions and during the superfusion with glutamate and GABA receptor antagonists. We showed that blocking the AMPA/kainate and NMDA glutamate receptors reduced to a different degree the eSPW frequency and neuronal firing associated with eSPWs. Only when applied simultaneously did the AMPA/kainate and NMDA receptor antagonists completely suppress eSPWs. At the same time, GABA(A) receptors appeared to have a limited role in eSPW generation as eSPWs persisted after GABA(A) receptor blockade alternating with recurrent epileptiform discharges; yet, eSPW amplitude was reduced after epileptiform activity onset. We also observed no changes in eSPW properties produced by blocking the GABA(B) receptors. Taken together, our findings reveal a predominant involvement of AMPA/kainate and NMDA glutamate receptors in eSPW generation and emphasize the role of eSPWs in providing conditions for NMDA receptor-mediated plasticity in the developing hippocampus.