Correlated Axonal Sprouting and Dendritic Spine Formation during Kainate-Induced Neuronal Morphogenesis in the Dentate Gyrus of Adult Mice

Abstract

Several examples of structural plasticity in the adult brain have been provided in the hippocampus, among which the most striking concerns axonal remodeling of the dentate gyrus granule cells. We have recently demonstrated that a single injection of kainic acid into the dorsal hippocampus of adult mice triggers a conspicuous morphogenetic response of granule cells. Cellular labeling with biocytin 1, 2, and 4 weeks after injection of kainate revealed a progressive increase in dendritic thickness and length (up to 2.5-times), combined with an increase in the number of dendritic spines. This correlation resulted in the conservation of total spine density. No modifications of the dendritic arborization pattern were noted. In addition to dendritic changes, the number of axonal profiles observed within the hypertrophied granular layer and the inner part of the molecular layer appeared dramatically increased. Timm staining and anterograde labeling of two of the main extra-hippocampal afferent systems (i.e., septal, entorhinal) evidenced sprouting of mossy fibers and of septal afferents. Entorhinal fibers were not obviously modified. As revealed by calretinin-immunohistochemistry, commissural afferents also responded by an extensive sprouting. In addition, increases of dendritic spine number and dendritic length were noticeably greater in portions of dendrites that receive mossy fiber collaterals and septal and hypothalamic afferents, than in the external portion which receives entorhinal afferents. Although qualitative, this correlation suggests a relationship between kainate-induced structural plasticity of mature granule cells and the specific capacities of afferent systems to elaborate axon collaterals.