Scaling of Network Excitability and Inhibition may Contribute to the Septotemporal Differentiation of Sharp...

The functional organization of the hippocampus along its longitudinal (septotemporal or dorsoventral) axis is conspicuously heterogeneous. This functional diversification includes the activity of sharp wave and ripples (SPW-Rs), a complex intrinsic network pattern involved in memory consolidation. In this study, using transverse slices from the ventral and the dorsal rat hippocampus and recordings of CA1 field potentials we studied the development of SPW-Rs and possible changes in local network excitability and inhibition, during in vitro maintenance of the hippocampal tissue. We found that SPW-Rs develop gradually in terms of magnitude and rate of occurrence in the ventral hippocampus. On the contrary, neither the magnitude nor the rate of occurrence significantly changed in dorsal hippocampal slices during their in vitro maintenance. The development of SPW-Rs was accompanied by an increase in local network excitability more in the ventral than in the dorsal hippocampus, and an increase in local network inhibition in the ventral hippocampus only. Furthermore, the amplitude of SPWs positively correlated with the level of maximum excitation of the local neuronal network in both segments of the hippocampus, and the local network excitability and inhibition in the ventral but not the dorsal hippocampus. Blockade of α5 subunit-containing GABA_A receptor by L-655,708 significantly reduced the rate of occurrence of SPWs and enhanced the probability of their generation in the form of clusters in the ventral hippocampus without affecting activity in the dorsal hippocampus. The present evidence suggests that a dynamic upregulation of excitation and inhibition in the local neuronal network may significantly contribute to the generation of SPW-Rs, particularly in the ventral hippocampus.