Spatial reference memory in normal aging Fischer 344 × Brown Norway F1 hybrid rats

McQuail, Joseph A.; Nicolle, Michelle M.

doi:10.1016/j.neurobiolaging.2014.06.030

Cited by 29 publications

(37 citation statements)

References 57 publications

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“…To assess age-related changes in spatial learning and memory in our experimental cohort, rats were first tested in the Morris water maze task using the standard procedures of Gallagher et al (1993), which have been implemented in multiple rat strains used to study cognitive aging (Bizon et al 2009;McQuail and Nicolle 2015). Young and aged rats were trained to locate a hidden platform over 8 d, with blocks of training trials interpolated by probe trials taking place every 2 d. Acquisition of an effective spatial search strategy was assessed based on cumulative integrated path lengths (CIPL) across successive blocks of training trials (Barnes et al 1996;Rosenzweig et al 1997;Burke et al 2010).…”

Section: Spatial Memory Is Impaired In Aged Ratsmentioning

confidence: 99%

“…Spatial memory abilities were assessed with probe tests on days 2, 4, 6, and 8 of the water maze paradigm (Gallagher et al 1993;Bizon et al 2009;McQuail and Nicolle 2015), in which the platform was lowered out of reach and rats were allowed to swim for 30 sec. Mean proximity to the learned platform location during each test was calculated and used as an index of targeted spatial search.…”

Section: Spatial Memory Is Impaired In Aged Ratsmentioning

confidence: 99%

“…Nevertheless, a subset of our young rats showed relatively poor spatial memory based on SLI values, while none of our aged rats had relatively good spatial memory based on SLI values (cf. McQuail and Nicolle 2015). This underscores the fact that SLI values from one laboratory are not necessarily comparable to those from another, even when the rat strain, water maze apparatus, and experimental protocol used are identical (McQuail and Nicolle 2015).…”

Section: Spatial Memory and Spatial Discrimination Abilities: Implicamentioning

confidence: 99%

“…McQuail and Nicolle 2015). This underscores the fact that SLI values from one laboratory are not necessarily comparable to those from another, even when the rat strain, water maze apparatus, and experimental protocol used are identical (McQuail and Nicolle 2015). It is possible that subtle variations in the experimental setup, including the prominence and distribution of extra-maze cues, biased rats toward using a less spatial and more response-based strategy during probe trials (Tomás .…”

Section: Spatial Memory and Spatial Discrimination Abilities: Implicamentioning

confidence: 99%

“…Parallel observations have been made in animal models of aging. Aged rats are impaired in spatial memory (Gallagher et al 1993;Bizon et al 2009;McQuail and Nicolle 2015), in discriminating between novel and familiar stimuli (Burke et al 2010(Burke et al , 2011, and in place learning when the learned target location is in close proximity to a foil location (Gracian et al 2013).…”

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confidence: 99%

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Discrimination performance in aging is vulnerable to interference and dissociable from spatial memory

et al. 2016

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Hippocampal-dependent episodic memory and stimulus discrimination abilities are both compromised in the elderly. The reduced capacity to discriminate between similar stimuli likely contributes to multiple aspects of age-related cognitive impairment; however, the association of these behaviors within individuals has never been examined in an animal model. In the present study, young and aged F344×BN F1 hybrid rats were cross-characterized on the Morris water maze test of spatial memory and a dentate gyrus-dependent match-to-position test of spatial discrimination ability. Aged rats showed overall impairments relative to young in spatial learning and memory on the water maze task. Although young and aged learned to apply a match-to-position response strategy in performing easy spatial discriminations within a similar number of trials, a majority of aged rats were impaired relative to young in performing difficult spatial discriminations on subsequent tests. Moreover, all aged rats were susceptible to cumulative interference during spatial discrimination tests, such that error rate increased on later trials of test sessions. These data suggest that when faced with difficult discriminations, the aged rats were less able to distinguish current goal locations from those of previous trials. Increasing acetylcholine levels with donepezil did not improve aged rats' abilities to accurately perform difficult spatial discriminations or reduce their susceptibility to interference. Interestingly, better spatial memory abilities were not significantly associated with higher performance on difficult spatial discriminations. This observation, along with the finding that aged rats made more errors under conditions in which interference was high, suggests that match-to-position spatial discrimination performance may rely on extra-hippocampal structures such as the prefrontal cortex, in addition to the dentate gyrus.

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Section: Spatial Memory Is Impaired In Aged Ratsmentioning

confidence: 99%

Section: Spatial Memory Is Impaired In Aged Ratsmentioning

confidence: 99%

Section: Spatial Memory and Spatial Discrimination Abilities: Implicamentioning

confidence: 99%

Section: Spatial Memory and Spatial Discrimination Abilities: Implicamentioning

confidence: 99%

mentioning

confidence: 99%

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Discrimination performance in aging is vulnerable to interference and dissociable from spatial memory

et al. 2016

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Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice

et al. 2018

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Introduction Centella asiatica is a plant used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates age‐related spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its mechanism of improving age‐related cognitive impairment. This study investigates the effects of CAW on a variety of cognitive tasks as well as on synaptic density and mitochondrial and antioxidant pathways.MethodsTwenty‐month‐old CB6F1 mice were treated with CAW (2 mg/ml) in their drinking water for 2 weeks prior to behavioral testing. Learning, memory, and executive function were assessed using the novel object recognition task (NORT), object location memory task (OLM), and odor discrimination reversal learning (ODRL) test. Tissue was collected for Golgi analysis of spine density as well as assessment of mitochondrial, antioxidant, and synaptic proteins.ResultsCAW improved performance in all behavioral tests suggesting effects on hippocampal and cortical dependent memory as well as on prefrontal cortex mediated executive function. There was also an increase in synaptic density in the treated animals, which was accompanied by increased expression of the antioxidant response gene NRF2 as well as the mitochondrial marker porin.ConclusionsThese data show that CAW can increase synaptic density as well as antioxidant and mitochondrial proteins and improve multiple facets of age‐related cognitive impairment. Because mitochondrial dysfunction and oxidative stress also accompany cognitive impairment in many pathological conditions this suggests a broad therapeutic utility of CAW.

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Rodent age‐related impairments in discriminating perceptually similar objects parallel those observed in humans

et al. 2017

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The ability to accurately remember distinct episodes is supported by high-level sensory discrimination. Performance on mnemonic similarity tasks, which test high-level discrimination, declines with advancing age in humans and these deficits have been linked to altered activity in hippocampal CA3 and dentate gyrus. Lesion studies in animal models, however, point to the perirhinal cortex as a brain region critical for sensory discriminations that serve memory. Reconciliation of the contributions of different regions within the cortical-hippocampal circuit requires the development of a discrimination paradigm comparable to the human mnemonic similarity task that can be used in rodents. In the present experiments, young and aged rats were cross-characterized on a spatial water maze task and two variants of an object discrimination task: one in which rats incrementally learned which object of a pair was rewarded and different pairs varied in their similarity (Experiment 1), and a second in which rats were tested on their ability to discriminate a learned target object from multiple lure objects with an increasing degree of feature overlap (Experiment 2). In Experiment 1, aged rats required more training than young to correctly discriminate between similar objects. Comparably, in Experiment 2, aged rats were impaired in discriminating a target object from lures when the pair shared more features. Discrimination deficits across experiments were correlated within individual aged rats, though, for the cohort tested, aged rats were not impaired overall in spatial learning and memory. This could suggest discrimination deficits emerging with age precede declines in spatial or episodic memory, an observation that has been made in humans. Findings of robust impairments in object discrimination abilities in the aged rats parallel results from human studies, supporting use of the developed tasks for mechanistic investigation of cortical-hippocampal circuit dysfunction in aging and disease.

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Spatial reference memory in normal aging Fischer 344 × Brown Norway F1 hybrid rats

Cited by 29 publications

References 57 publications

Discrimination performance in aging is vulnerable to interference and dissociable from spatial memory

Discrimination performance in aging is vulnerable to interference and dissociable from spatial memory

Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice

Rodent age‐related impairments in discriminating perceptually similar objects parallel those observed in humans

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