title: Unilateral entorhinal denervation leads to long-lasting dendritic alterations of mouse hippocampal granule cells.
abstract: 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 (3d, 7d, 10d, 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.
authors.affiliation: Institute of Clinical Neuroanatomy, Neuroscience Center, Goethe-University, D-60590 Frankfurt/Main, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Vuksic
authors.forename: Domenico
authors.initials: D
authors.lastname: Del Turco
authors.forename: Andreas
authors.initials: A
authors.lastname: Vlachos
authors.forename: Gerlind
authors.initials: G
authors.lastname: Schuldt
authors.forename: Christian M
authors.initials: CM
authors.lastname: Müller
authors.forename: Gaby
authors.initials: G
authors.lastname: Schneider
authors.forename: Thomas
authors.initials: T
authors.lastname: Deller
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D003712:Dendrites / Q000502:physiology*; D003714:Denervation / Q000379:methods*; D018728:Entorhinal Cortex / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology*; D019580:Perforant Pathway / Q000601:surgery*; D018709:Statistics, Nonparametric
chemical_list: D000110:Acetylcholinesterase