Aged rats with intact memory show distinctive recruitment in cortical regions relative to young adults in a cue mismatch task.

Abstract

Similar to elderly humans, aged Long–Evans rats exhibit individual differences in performance on tasks that critically depend on the medial temporal lobe memory system. Although reduced memory performance is common, close to half of aged rats in this outbred rodent population perform within the range of young subjects, exhibiting a stable behavioral phenotype that may signal a resilience to memory decline. Increasing evidence from research on aging in the Long–Evans study population supports the existence of adaptive neural change rather than avoidance of detrimental effects of aging on the brain, indicating a malleability of brain function over the life span that may preserve optimal function. Augmenting prior work that centered on hippocampal function, the current study extends investigation to cortical regions functionally interconnected with the hippocampal formation, including medial temporal lobe cortices and posterior components of the default mode network. In response to an environmental manipulation that creates a mismatch in the expected cue orientation, aged rats with preserved memory show greater activation across an extended network of cortical regions as measured by immediate early gene expression. In contrast, young subjects, behaviorally similar to the aged rats in this study, show a more limited cortical response. This distinctive cortical recruitment in aged unimpaired rats, set against a background of comparable activation across hippocampal subregions, may represent adaptive cortical recruitment consistent with evidence in human studies of neurocognitive aging.

Decreased investigatory head scanning during exploration in learning-impaired, aged rats

“…This result indicated preserved recognition by the AU animals of spatial environmental change. The increase in scanning rate in the mismatch session was accompanied by similar increases in the activity of excitatory neurons in the hippocampus (Branch et al, 2019) and other cortical regions (Haberman et al, 2019) for both YG and AU rats, as measured by zif-268 expression. However, the expression of the inhibitory gene marker for the GABA-enzyme GAD1 was increased in the hippocampus in AU rats only (Branch et al, 2019).…”

“…A prior finding that place field formation or strength is influenced by head scanning (Monaco et al, 2014) suggests that incoming environmental information during scanning behavior is being incorporated into a hippocampal representation of place. Other methods have been used to assess activity in hippocampal and related cortical regions related to investigatory behavior in a simplified version of the DR protocol (Branch et al, 2019;Haberman et al, 2019). In these studies, scanning rates in AU animals and YG animals were comparable in standard sessions, and were similarly elevated during the single 180° mismatch condition relative to baseline.…”

“…For the spatial version of the water maze task, the animals were given 3 trials per day for 8 days, in which the submerged escape platform was in a constant position in the tank (Branch et al, 2019;Haberman et al, 2019). The water temperature was 27° C. The release location in the tank was varied from trial to trial.…”

“…However, this behavior occurs at decision points in relation to future fixed reward sites and thus may be qualitatively distinct from head scanning as observed during exploration. Recently, it was shown that AU rats showed head-scanning frequency comparable to young rats in a double-rotation, local-global cue mismatch manipulation that is amenable to identifying clear epochs of head scanning behavior (Branch et al, 2019;Haberman et al, 2019). This preservation of scanning behavior in the aged animals was correlated with increases in inhibitory interneuron activity as a potential compensatory mechanism to counteract the hyperactivity that has been reported in aged hippocampus (Branch et al, 2019).…”

Decreased investigatory head scanning during exploration in learning-impaired, aged rats

“…This result indicated preserved recognition by the AU animals of spatial environmental change. The increase in scanning rate in the mismatch session was accompanied by similar increases in the activity of excitatory neurons in the hippocampus (Branch et al, 2019) and other cortical regions (Haberman et al, 2019) for both YG and AU rats, as measured by zif-268 expression. However, the expression of the inhibitory gene marker for the GABA-enzyme GAD1…”