Behavioral pattern separation performance and hippocampal doublecortin neuron analysis in very old female rats

Abstract

Aging is associated with impaired performance in behavioral pattern separation (PS) tasks based on similarities in object features and in object location. Hippocampal dentate gyrus (DG) is required for PS. DG is thought to preprocess information, which facilitates pattern completion in the CA3 region. In order to evaluate the effect of aging on discrimination of overlapping memories of object location or features, we assessed three groups of rats: Young (Y, 4-5 mo., n= 25), Middle Aged (MA, 18 mo., n= 32) and Senile (S, 28 mo., n= 13). Experiment 1: spontaneous location recognition (SLR) and Experiment 2: spontaneous object recognition (SOR). The testing chamber for SLR was a black circular arena (90 cm diameter) and for SOR was a white triangular arena (60 cm per side). On the SLR sample phase, rats were exposed to three identical objects (A1, A2, and A3). On the choice phase, rats were exposed to two identical objects (A4 and A5). A4 was placed in a familiar location and A5 was placed in a new location. On the SOR sample phase, three different objects were assembled (AB, BC, and DE). On the choice phase, a novel object was assembled in AC (two non-shared features of the objects in the sample phase), and the familiar object was a copy of DE. Morphometric analysis revealed a significant age-related reduction in doublecortin (DCX) cell number (MA and S) but only the S rats presented DCX neuron diameter reduction in the DG. In the SLR, the discriminatory performance was markedly deteriorated in the MA and S rats versus Y rats. In the SOR, only S rats presented deterioration in memory disambiguation. However, MA rats showed a preserved memory as compared with Y rats. These findings reveal the existence of a significant vulnerability of DCX neurons to age in rats and a deficient DG neurogenesis-related object location discrimination. Furthermore, the overlapping memories involving object location are more sensitive to age than overlapping memories involving features.