Unilateral entorhinal denervation leads to long-lasting dendritic alterations of mouse hippocampal granule cells

Following brain injury, neurons efferently connected from the lesion site are denervated and remodel their dendritic tree. Denervation-induced dendritic reorganization of granule cells was investigated in the dentate gyrus of the Thy1-GFP mouse. After mechanical transection of the perforant path, single granule cells were 3D-reconstructed at different time points post-lesion (3 d, 7 d, 10 d, 30 d, 90 d and 180 d) and their soma size, total dendritic length, number of dendritic segments and dendritic branch orders were studied. Changes in spine densities were determined using 3D-analysis of individual dendritic segments. Following entorhinal denervation the granule cell arbor progressively atrophied until 90 d post-lesion (reduction of total dendritic length to ~ 50% of control). Dendritic alterations occurred selectively in the denervated outer molecular layer, where a loss of distal dendritic segments and a reduction of mean segment length were seen. At 180 d post-lesion total dendritic length partially recovered (~ 70% of control). This recovery appeared to be the result of a re-elongation of surviving dendrites rather than dendritic re-branching, since the number of dendritic segments did not recover. In contrast to the protracted dendritic changes, spine density changes followed a faster time course. In the denervated layer spine densities dropped to ~ 65% of control values and fully recovered by 30 d post-lesion. We conclude that entorhinal denervation in mouse causes protracted and long-term structural alterations of the granule cell dendritic tree. Spontaneously occurring reinnervation processes, such as the sprouting of surviving afferent fibers, are insufficient to maintain the granule cell dendritic arbor.

► 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.