Increased molecular plasticity along the septotemporal axis of the hippocampus is associated with network functioning

Abstract

Molecular plasticity crucially supports adaptive cellular and network functioning in the brain. Variations in molecular plasticity may yield important differences in neuronal network dynamics between discrete brain subregions. In the present study we show that the gradual development of sharp waves (SPWs), a spontaneous network activity that is organized under normal in vitro conditions in the CA1 field of ventral but not dorsal hippocampal slices, is associated with region selective molecular reorganization. In particular, increased levels of mRNAs for specific GABA A receptor subunits (α1, β2, γ2) occurred in ventral hippocampal CA1 field during the development of SPWs. These mRNA changes were followed by a clear increase in GABA A receptor number in ventral hippocampus, as shown by [ 3 H]muscimol binding. An increase in mRNAs was also observed in dorsal slices for α2 and α5 subunits, not followed by quantitative GABA A receptor changes. Furthermore, full development of SPWs in the CA1 field (at 3 hours of slice maintenance in vitro) was followed by increased expression of immediate early genes c-fos and zif-268 in ventral hippocampal slices (measured at 5 hours in vitro). No change in c-fos and zif-268 levels is observed in the CA1 field of dorsal slices, which do not develop spontaneous activity. These results suggest that generation of SPWs could trigger specific molecular reorganization in the VH that may be related to the functional roles of SPWs. Correspondingly, the revealed increased potentiality of the ventral hippocampus for molecular reorganization may provide a clue to mechanisms that underlie the regulated emergence of SPWs along the longitudinal axis of the hippocampus. Furthermore, the present evidence suggests that dynamic tuning between spontaneous neuronal activity and molecular organization may importantly contribute to the functional segregation/heterogeneity seen along the hippocampus.