Deficits across multiple cognitive domains in a subset of aged Fischer 344 rats

LaSarge, Candi L.; Montgomery, Karienn S.; Tucker, Catherine; Slaton, G. Simona; Griffith, William H.; Setlow, Barry; Bizon, Jennifer L.

doi:10.1016/j.neurobiolaging.2006.04.010

Cited by 64 publications

(89 citation statements)

References 34 publications

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“…LaSarge et al [23] reported that spatial reference memory is correlated with olfactory discrimination learning ability, such that among aged rats, poor performance in the reference memory task described here is correlated with impaired odor discrimination abilities. These odor discrimination impairments were not due to anosmia nor were they reflective of global mnemonic impairments, as aged mnemonically impaired rats were able to learn non-olfactory discriminations as well as young rats.…”

Section: Discussionmentioning

confidence: 60%

Spatial reference and working memory across the lifespan of male Fischer 344 rats

Bizon

LaSarge

Montgomery

et al. 2009

Neurobiology of Aging

134

183

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Loss of mnemonic function is among the earliest and most disconcerting consequences of the aging process. This study was designed to provide a comprehensive profile of spatial mnemonic abilities in male Fischer 344 (F344) rats across the lifespan. Young, middle-aged, and aged F344 rats were trained in spatial reference and working memory versions of the water maze task. There was a progressive age-related decline in spatial reference memory across the lifespan. Reliable individual differences were observed among aged rats, with some aged rats performing as well as young cohorts and other performing outside this range. An age-related delay-dependent decline was observed on a working memory version of the water maze task although no relationship between performance on reference and working memory tasks was present. Notably, middle-aged rats were impaired relative to young on both tasks. Together these data demonstrate that individual differences in spatial reference memory exist among aged F344 rats and provide novel data demonstrating an unrelated decline in working memory across the lifespan, suggesting that age-related mnemonic dysfunction may occur across multiple brain systems.

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Section: Discussionmentioning

confidence: 60%

Spatial reference and working memory across the lifespan of male Fischer 344 rats

Bizon

LaSarge

Montgomery

et al. 2009

Neurobiology of Aging

134

183

View full text Add to dashboard Cite

show abstract

“…Olfactory deficits reported in aging rodents include alterations of acuity, discrimination, and memory, although changes are variable depending on the paradigm (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Olfactory information processing involves successively the OE, OB, and piriform cortex.…”

Section: Are Morphological Changes In the Ob Related To Alterations Inmentioning

confidence: 99%

Age-induced disruption of selective olfactory bulb synaptic circuits

Richard

Taylor²,

Greer³

2010

Proc. Natl. Acad. Sci. U.S.A.

127

125

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Little is known about how normal aging affects the brain. Recent evidence suggests that neuronal loss is not ubiquitous in aging neocortex. Instead, subtle and still controversial, region-and layerspecific alterations of neuron morphology and synapses are reported during aging, leading to the notion that discrete changes in neural circuitry may underlie age-related cognitive deficits. Although deficits in sensory function suggest that primary sensory cortices are affected by aging, our understanding of the age-related cellular and molecular changes is sparse. To assess the effect of aging on the organization of olfactory bulb (OB) circuitry, we carried out quantitative morphometric analyses in the mouse OB at 2, 6, 12, 18, and 24 mo. Our data establish that the volumes of the major OB layers do not change during aging. Parallel to this, we are unique in demonstrating that the stereotypic glomerular convergence of M72-GFP OSN axons in the OB is preserved during aging. We then provide unique evidence of the stability of projection neurons and interneurons subpopulations in the aging mouse OB, arguing against the notion of an age-dependent widespread loss of neurons. Finally, we show ultrastructurally a significant layer-specific loss of synapses; synaptic density is reduced in the glomerular layer but not the external plexiform layer, leading to an imbalance in OB circuitry. These results suggest that reduction of afferent synaptic input and local modulatory circuit synapses in OB glomeruli may contribute to specific age-related alterations of the olfactory function.aging | axodendritic synapses | dendrodendritic synapses | mitral cells A ge-related neurodegenerative diseases, such as Parkinson and Alzheimer's, involve localized or widespread neuronal loss, but little is known about the changes occurring in the brain during normal aging. A growing consensus argues against widespread neuronal loss and atrophy during aging (1, 2). Rather, subtle region-and layer-specific alterations of neuronal morphology and synaptic connections are reported in the neocortex and hippocampus, where they may contribute to age-related cognitive deficits.The laminar organization of olfactory bulb (OB) neurons and synapses provides a simplified cortical model in which we can probe principles of neuronal and synaptic organization during aging. Sensory functions are affected by aging, including alterations in olfactory acuity, discrimination, and memory (3-12). The OB is the first central relay in the pathway processing odor information: it receives afferent input from olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) and is responsible for detecting odors in the nasal cavity. OSN axons synapse on mitral/tufted cell dendrites in OB glomerular neuropils. OB local interneurons modulate the activity of mitral/tufted cells, contributing to odor signal integration, before propagation to the piriform cortex. Projections from the OE to the OB are organized in an odor receptor (OR) map; each subpopulation of OSNs expressin...

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“…On the day prior to shaping, each rat was given five 45 mg food pellets in its home cage to reduce neophobia to the food reward used in the task. Shaping procedures for the probability discounting task followed those used previously (Cardinal et al, 2000;LaSarge et al, 2007;. Shaping began with a 64-min session of magazine training consisting of 38 deliveries of a single food pellet with an inter-trial interval (ITI) of 100 ± 40 s. Following magazine training, rats were trained to press a single lever (either the left or right, counterbalanced across groups; the other lever was retracted during this phase of training) to receive a single food pellet.…”

Section: Methodsmentioning

confidence: 99%

“…Spatial reference memory was assessed as described previously (LaSarge et al, 2007;Bizon et al, 2009). Briefly, rats received three daily training trials with a 30-s ITI over eight consecutive days.…”

Section: Methodsmentioning

confidence: 99%

“…As in humans, there are robust individual differences in cognitive performance among aged rats (Gallagher et al, 1993;Barense et al, 2002;Schoenbaum et al, 2006;LaSarge et al, 2007;Bizon et al, 2009). Because the laboratory rearing environment is largely homogeneous, these individual differences in cognitive aging can be largely dissociated from experiential factors in a way that is difficult to achieve in human populations.…”

Section: Wwwfrontiersinorgmentioning

confidence: 99%

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