DYNAMICS OF THE ACTIVITY-RELATED PROTEIN <EM >ARC </EM>DURING DENDRITIC SPINE REMODELING IN HIPPOCAMPAL GRANULE CELLS AFTER PERFORANT PATH TRANSECTION

Neuronal damage resulting from neurodegenerative diseases or traumatic brain injury occurs both locally and in functionally connected cortical regions due to axonal degeneration and subsequent loss of synaptic connectivity. To study dendritic spine reorganization and to reveal recent history of dendritic spine activity, we used an entorhinal cortex lesion model and analyzed the presence of the activity-regulated cytoskeleton-associated protein (Arg3.1/Arc) as a molecular marker of neuronal activation. We performed stereotaxic entorhino-hippocampal denervation in C57Bl/6 male young adult mice followed by intracellular fluorescent dye injections, immunofluorescence, and confocal microscopy to assess dentate gyrus granule cell dendritic spine structural dynamics in denervated and non-denervated molecular layer portions during the first month post-lesion. We found an increase in the proportion of Arc-positive spines and a reduced density of Arc-negative spines in the denervated layer three days post-lesion returning to baseline by fourteen days, while the non-denervated layer showed no changes. However, an interesting location-dependent difference was observed in the increase of average spine sizes of Arc-negative spines. In the denervated portion, the effect peaked at three days post-lesion, whereas in the non-denervated portion the increase was delayed, peaking at seven days and returning to baseline fourteen days post-lesion. These findings indicate that Arc protein dynamics in granule cell spines are altered after entorhinal cortex lesion, with the pattern reflecting either a relative resilience of Arc-positive spines to denervation-induced elimination or an increase in recent synaptic activity of surviving spines that supports dendritic and network stabilization following substantial spine loss.