Excitatory granule cells of the dentate gyrus exhibit a double inhibitory neurochemical content after intrahippocampal administration of kainate in adult mice.

ABSTRACT

We have previously demonstrated that, in the adult mouse, injection of kainate/AMPA receptors agonists into the dorsal hippocampus induces major structural modifications of the dentate gyrus granule cells. Such changes are mediated by the brain-derived neurotrophic factor (BDNF). Considering previous involvements of BDNF in activity-linked regulations of hippocampal neuronal phenotype, changes of neurochemical contents were further investigated. It is shown that excitatory granule cells rapidly acquire a strong immunoreactivity for the inhibitory neurotransmitters GABA and neuropeptide-Y, with different patterns for both molecules. GABA immunoreactivity appeared first in mossy fibers, before extending to cell bodies and dendrites. Analysis of glutamic acid decarboxylase revealed slight increases in mossy fibers and no somatic labeling. In contrast to GABA, neuropeptide-Y labeling was observed first in granule cell soma and then in mossy fibers, with a centrifugal gradient. All labelings were transient, but slight amounts of GABA and NPY were kept in some cell bodies for at least 6 months. Confocal microscope analysis of double GABA/NPY labelings revealed colocalization of both mediators in the same neurons. The specificity of kainate-linked changes was suggested by lack of immunoreactivity for somatostatin. These results show that the capacities of mature granule cells to adapt environmental modifications can concern neurochemical contents, by synthesis and/or uptake of specific molecules. The fact that adaptive changes are rapid and transient suggests a direct response to kainate, in order to limit its potentially deleterious effects. Colocalization of GABA and neuropeptide-Y indicates that the dentate gyrus granule cells can use several pathways to this aim.