Dendritic remodeling of dentate granule cells following a combined entorhinal cortex/fimbria fornix lesion.

This study examined the time course of dendritic reorganization of dentate granule neurons of the hippocampus following the loss of input from both the fimbria fornix (FF) and the entorhinal cortex (EC). We used the Golgi-Cox stain to assess the morphology of dentate granule neurons at six postlesion time points (4, 8, 14, 30, 45, and 60 days) and dendritic measures included total dendritic length, number of segments, number of branch points, and spine density. We found that as early as 4 days postlesion, total dendritic length and number of segments were significantly decreased with the greatest change occurring in the distal parts of the dendritic arbor located in the outer molecular layer of the dentate gyrus. Dendritic measures related to segment number and dendritic length returned to 70% of intact values by 30 days postlesion and were not significantly different from unlesioned rats at 45 and 60 days postlesion. In contrast, the recovery of spine density was transient. Spine density in the outer molecular layer of the dentate gyrus decreased by 60% at 4 days postlesion and returned to 87% of intact values by 30 days postlesion. However, there was a second loss of dendritic spines along the distal portion of the dendrite between 30 and 60 days postlesion. These data provide evidence that the ability of granule neurons to recover a dendritic morphology similar to that of unlesioned rats is impaired following the combined EC/FF lesion and that the "secondary loss" of dendritic spine density on granule neurons may significantly limit the chances of the hippocampus reforming a synaptic circuitry that could lead to functional recovery after the EC/FF lesion.