Age-related impairments in object-place associations are not due to hippocampal dysfunction.

Abstract

Age-associated cognitive decline can reduce an individual’s quality of life. As no single neurobiological deficit can account for the wide spectrum of behavioral impairments observed in old age, it is critical to develop an understanding of how interactions between different brain regions change over the life span. The performance of young and aged animals on behaviors that require the hippocampus and cortical regions to interact, however, has not been well characterized. Specifically, the ability to link a spatial location with specific features of a stimulus, such as object identity, relies on the hippocampus, perirhinal and prefrontal cortices. Although aging is associated with dysfunction in each of these brain regions, behavioral measures of functional change within the hippocampus, perirhinal and prefrontal cortices in individual animals are often not correlated. Thus, how dysfunction of a single brain region within this circuit, such as the hippocampus, impacts behaviors that require communication with the perirhinal and prefrontal cortices remains unknown. To address this question, young and aged rats were tested on the interregion dependent object-place paired association task, as well as a hippocampal-dependent test of spatial reference memory. This particular cohort of aged rats did not show deficits on the hippocampal-dependent task, but were significantly impaired at acquiring object-place associations relative to young. These data suggest that behaviors requiring functional connectivity across different regions of the memory network may be particularly sensitive to aging, and can be used to develop models that will clarify the impact of systems-level dysfunction in the elderly.

Medial prefrontal-perirhinal cortical communication is necessary for flexible response selection

“…During the initial training sessions on the OPPA task, rats exhibit a “side bias” for selecting the object over a well on a particular side, regardless of the object or the arm of the maze (Hernandez et al, 2015; Jo and Lee, 2010a; Lee and Byeon, 2014; Lee and Kim, 2010). This bias has to be suppressed, presumably through mPFC activity projecting back to sensorimotor areas (Lee and Byeon, 2014) before OPPA task performance shows an improvement.…”

“…Additionally, blocking glutamatergic transmission in the mPFC enhances impulsivity and leads to compulsive perseveration in rats (Carli, Baviera, Invernizzi, and Balducci, 2006). Rats show a significant side bias during the acquisition of the OPPA task and inhibiting this perseveration is essential to being able to learn the object-in-place rule (Hernandez et al, 2015; Lee and Byeon, 2014). Although rats may not stop displaying a side bias, in the days after acquisition of the rule, they may show inhibitory behavior towards the object on the preferred side.…”

“…For all experiments, a two-arm maze constructed from wood and sealed with waterproof black paint was used (Figure 1A; Hernandez et al, 2015). The two arms of the maze were separated by black poster board with distinctive markings on each side to prevent the rat from seeing the opposite arm while providing environmental cues to differentiate the two arms.…”

“…Rats were trained to use an object-in-place rule, in which the rewarded object of a pair was contingent on the spatial location (see, Hernandez, Maurer, Reasor, Turner, Barthle, Johnson, et al, 2015; Lee and Solivan, 2008) prior to surgery for cannula placement. Rats began the trial in either the left or right arm of the maze, randomly chosen.…”

“…Rats often display response biases during the acquisition of the OPPA task prior to learning the object-in-place rule (Hernandez et al, 2015; Jo and Lee, 2010a; b; Lee and Byeon, 2014). Thus, indices of a side bias (left vs. right well) and object bias (e.g.…”