Cortical network dynamics are coupled with cognitive aging in rats

Abstract

Changes in neuronal network activity and increased interindividual variability in memory are among the most consistent features of growing older. Here, we examined the relationship between these hallmarks of aging. Young and aged rats were trained on a water maze task where aged individuals reliably display an increased range of spatial memory capacities relative to young. Two weeks later, neuronal activity was induced pharmacologically with a low dose of pilocarpine and control animals received vehicle. Activity levels were proxied by quantifying the immediate early gene products Arc and c‐Fos. While no relationship was observed between basal, resting activity, and individual differences in spatial memory in any brain region, pilocarpine‐induced marker expression was tightly coupled with memory in all areas of the prefrontal cortex (PFC) and hippocampus examined. The nature of this association, however, differed across regions and in relation to age‐related cognitive outcome. Specifically, in the medial PFC, induced activity was greatest in aged rats with cognitive impairment and correlated with water maze performance across all subjects. In the hippocampus, the range of induced marker expression was comparable between groups and similarly coupled with memory in both impaired and unimpaired aged rats. Together the findings highlight that the dynamic range of neural network activity across multiple brain regions is a critical component of neurocognitive aging.

Differential Retinoic Acid Signaling in the Hippocampus of Aged Rats with and without Memory Impairment

“…1 A ]. Consistent with many earlier studies ( Lee et al, 2005 ; Castellano et al, 2012 ; Fletcher et al, 2014 ; Myrum et al, 2019 ), the aged group exhibited substantially increased variability such that some rats performed on par with Y, while others performed well outside the normal range. Aged animals with LI scores below 240 ( n = 15) were classified as AU, and rats that scored above 240 ( n = 17) were operationally defined AI.…”

Transcranial Laser Photobiomodulation Improves Intracellular Signaling Linked to Cell Survival, Memory and Glucose Metabolism in the Aged Brain: A Preliminary Study

“…However, little is known about the effects of PBM on the old brain without the disease. Another important point is the inter-individual variability observed during aging (Nyberg, 2017;Myrum et al, 2019). However, our results corroborate studies using laser treatment in other tissues (Kim et al, 2017;Tani et al, 2018;Wang et al, 2021).…”

Age-Related Memory Impairment Is Associated with Increased zif268 Protein Accumulation and Decreased Rpt6 Phosphorylation

“…This was not the case in the mPFC, aRSC, and the DH. Interestingly, all regions of interest showed an association between freezing during the test and zif268 expression where lower levels of freezing were associated with higher levels of zif268 expression, except for the DH [ 6 ] and the aRSC. These results are also consistent with hypotheses that suggest age-related memory impairments result from an increase in IEG accumulation as a result of reduced proteolytic activity and subsequent protein degradation rather than an overall decrease in number of neurons [ 35 , 62 ].…”

“…Normal human aging is accompanied by several changes in cognitive function [ 1 ], including impairments in memory formation and retention [ 2 , 3 ]. Age-related deficits have also been observed in the rodent literature, with aged animals demonstrating impairments in several memory paradigms, including the Morris water maze [ 4 , 5 , 6 , 7 ], the radial arm maze [ 8 , 9 ], active and passive avoidance learning [ 9 , 10 , 11 ], object recognition [ 12 ], and the objects in updated locations task [ 13 ]. Maintaining unimpaired cognitive ability in older adults is considered one of the major components to healthy aging [ 14 ], and understanding the neurobiological mechanisms that contribute to cognitive dysfunction is crucially important to facilitating healthy aging in a senescent human population [ 15 ].…”

“…The TFC circuit includes the hippocampus [ 20 , 21 , 22 , 23 ], retrosplenial cortex (RSC; [ 24 , 25 , 26 ]), and medial prefrontal cortex (mPFC; [ 27 , 28 ]) in addition to brain areas such as the lateral amygdala (LA) and the ventrolateral periaqueductal gray (vlPAG), which are also necessary for the delay version of the procedure [ 29 , 30 ]. Interestingly, the basolateral amygdala (BLA; [ 16 ]), dorsal hippocampus (DH; [ 16 , 31 ]), ventral hippocampus (VH; [ 31 ]), mPFC [ 6 , 16 , 32 ], and RSC [ 33 ] all show neurobiological changes in aged rodents relative to their young-adult counterparts. These changes range from impairments in protein degradation associated with memory retrieval [ 16 ] to changes in resting state neural activity [ 33 ].…”