Modeling behavioral recovery following lesion induction in the rat dentate gyrus

Unilateral entorhinal lesions have enjoyed immense popularity as a model of recovery from damage. In part, the popularity has been supported the laminar organization of the hippocampal formation, which allows for the dissection of the contribution of individual afferent pathways to the recovery process. The commissural/associational pathway is of particular interest, since electrophysiological and gross anatomical data, although limited, have correlated sprouting in this pathway with behavioral recovery. Unfortunately, information relating recovery to synaptic structure is lacking. Addressing this issue, two analyses were conducted. Initially, a quantitative review of the literature reporting behavioral recovery following this type of lesion was conducted using meta-analytic techniques. Using this detailed information across decades of research, multiple linear regression analysis was conducted to address whether the morphological correlates of recovery could predict behavioral recovery. This resulted in an equation relating morphology and recovery that stood up well to several diagnostic tests. Moreover, this model suggests that synapse structure (in particular, synapse size and curvature, as well as terminal compartmentalization and the density of multi-synaptic terminals) holds a greater potential to predict behavioral recovery than increases in synapse number, which is typically seen as the optimal anatomical measure of recovery. This initial attempt to identify, quantify, and validate a model of lesion recovery is an important initial step in understanding how synaptic morphology may help mediate recovery of function.