Unilateral entorhinal denervation leads to long-lasting dendritic alterations of mouse hippocampal granule cells
Highlights
► Long-term survival study of dendritic remodeling after denervation in mouse. ► Denervation causes loss of distal dendritic segments and a reduction of mean segment length. ► Dendritic alterations are protracted and occur over the course of months. ► Denervation causes transient and layer-specific changes in spine density. ► Denervation has long-lasting effects on the complexity of the dendritic tree.
Section snippets
Animals and tissue preparation
Adult male Thy1-GFP transgenic mice (Thy1-GFP-M line; C57BL/6 background; Feng et al., 2000; N = 33; Fig. 1) housed under standard laboratory conditions were used. Experimental animals were divided into three groups: control animals 4–5 months (N = 5), control animals 11–12 months (N = 5) and animals with unilateral wire knife transections of the perforant path (N = 23). Animals were allowed to survive 3, 7, 10, 30, 90 and 180 d prior to morphological analysis (see Table 1 for details concerning number of
The fascia dentata of the normal (non-denervated) Thy1-GFP mouse
Using fluorescence microscopy, a subpopulation of intensely green-fluorescent granule cells was revealed in the fascia dentata of Thy1-GFP mice (Figs. 1A, B). These neurons were located in the granule cell layer and could be identified based on morphological criteria, i. e. small ovoid somata, apically oriented spiny dendrites extending all the way to the hippocampal fissure and a basally oriented axon originating from the granule cell soma and extending into the hilus (Desmond and Levy, 1982,
Discussion
In the present study, we investigated the reorganization of dentate granule cells after entorhinal denervation in Thy1-GFP mouse mutants. The main results are: (1) Entorhinal denervation caused a profound reorganization of the dendritic tree of dentate granule cells. Atrophic changes occurred primarily in the denervated zone of the molecular layer, where a significant shortening of dendrites and a loss of dendritic segments was seen. (2) Dendritic atrophy progressed until ~ 90 d post-lesion. By
Acknowledgments
The authors thank Anke Biczysko, Heike Korff, and Charlotte Nolte-Uhl for excellent technical support, Dr. Guoping Feng for providing the Thy1-GFP mice, and Dr. Peter Jedlicka for reading and commenting on the manuscript. Supported by Deutsche Forschungsgemeinschaft (DFG) and LOEWE Lipid Signaling Forschungszentrum Frankfurt (LiFF).
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These authors contributed equally to this work.
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Present address: Max-Planck-Institute for Brain Research, Deutschordenstraße 46, 60528 Frankfurt am Main, Germany.