Aging-related changes in calcium-binding proteins in rat perirhinal cortex

Moyer, James R.; Furtak, Sharon C.; McGann, John P.; Brown, Thomas H.

doi:10.1016/j.neurobiolaging.2009.10.001

Cited by 37 publications

(26 citation statements)

References 93 publications

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“…This age-associated decline in stimulus recognition is reminiscent of the object recognition impairments that have been reported for rats with perirhinal cortical (PRC) lesions (Bartko et al, 2007; McTighe et al, 2010), and suggests that the PRC is among the brain structures vulnerable to the process of normal aging (Burke et al, 2012a; Liu et al, 2008; Liu et al, 2009; Moyer et al, 2009). Although data from animals with a compromised PRC have suggested that it is critically involved in object recognition memory (Winters and Bussey, 2005), the neurobiological mechanism that supports this cognitive process is not completely understood.…”

Section: Introductionmentioning

confidence: 69%

Layer V perirhinal cortical ensemble activity during object exploration: A comparison between young and aged rats

et al. 2012

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Object recognition memory requires the perirhinal cortex (PRC) and this cognitive function declines during normal aging. Recent electrophysiological recordings from young rats have shown that neurons in layer V of the PRC are activated by 3-dimensional objects. Thus, it is possible that age-related object recognition deficits result from alterations in PRC neuron activity in older animals. To examine this, the present study used cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) with confocal microscopy to monitor cellular distributions of activity-induced Arc RNA in layer V of the PRC. Activity was monitored during two distinct epochs of object exploration. In one group of rats (6 young/6 aged) animals were placed in a familiar testing arena and allowed to explore five different 3-dimensional objects for two 5-min sessions separated by a 20-min rest (AA). The second group of animals (6 young/6 aged) also explored the same objects for two 5-min sessions, but the environment was changed between the first and the second epoch (AB). Behavioral data showed that both age groups spent less time exploring objects during the second epoch, even when the environment changed, indicating successful recognition. Although the proportion of active neurons between epochs did not change in the AA group, in the AB group more neurons were active during epoch 2 of object exploration. This recruitment of neurons into the active neural ensemble could serve to signal that familiar stimuli are being encountered in a new context. When numbers of Arc positive neurons were compared between age groups, the old rats had significantly lower proportions of Arc-positive PRC neurons in both the AA and AB behavioral conditions. These data support the hypothesis that age-associated functional alterations in the PRC contribute to declines in stimulus recognition over the lifespan.

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Section: Introductionmentioning

confidence: 69%

Layer V perirhinal cortical ensemble activity during object exploration: A comparison between young and aged rats

et al. 2012

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“…3C & D, red fluorescence), immunofluorescence in olfactory bulbs on the Mn-exposed side was also not different from that in bulbs on the vehicle-exposed side (mean 96 ± 3% of control, one-sample t-test, p = 0.28). These proteins have both been reported to exhibit significant plasticity in response to olfactory nerve damage (Philpot et al, 1997, Baker et al, 1988) or senescence (Choi et al, 2010; Moyer et al, 2011), but changes in their expression patterns do not appear to contribute to the observed changes in olfactory nerve function. However, we cannot rule out the possibility that Mn-exposure alters the activity of TH independent of its expression (Lehmann et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo

et al. 2012

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Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled manganese can bypass the blood-brain barrier and reach the central nervous system by transport down the olfactory nerve to the brain’s olfactory bulb. However, the mechanism by which Mn disrupts neural function remains unclear. Here we used optical imaging techniques to visualize exocytosis in olfactory nerve terminals in vivo in the mouse olfactory bulb. Acute Mn exposure via intranasal instillation of 2–200 μg MnCl2 solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 μg MnCl2 and a 90% reduction compared to vehicle controls with a 200 μg exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn’s action is occurring centrally, not peripherally. This is the first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases in the basal ganglia despite normal levels of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn’s action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects.

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“…The perirhinal cortex of aged animals undergoes numerous changes that include reduced neural activity in response to stimuli (Burke et al, 2012a, 2014; Ryan et al, 2012) and alterations in protein expression (Liu et al, 2008a,b, 2009; Moyer et al, 2011), which could account for age-related deficits in perceptual discrimination. A next step in this line of research will be to determine if the individual differences in olfactory discrimination deficits reported here are paralleled in other sensory modalities, as one would expect as a consequence of age-related alterations in perirhinal cortical encoding.…”

Section: Discussionmentioning

confidence: 99%

Interaction between age and perceptual similarity in olfactory discrimination learning in F344 rats: relationships with spatial learning

Yoder

Gaynor

Burke

et al. 2017

Neurobiology of Aging

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Emerging evidence suggests that aging is associated with a reduced ability to distinguish perceptually similar stimuli in one’s environment. As the ability to accurately perceive and encode sensory information is foundational for explicit memory, understanding the neurobiological underpinnings of discrimination impairments that emerge with advancing age could help elucidate the mechanisms of mnemonic decline. To this end, there is a need for preclinical approaches that robustly and reliably model age-associated perceptual discrimination deficits. Taking advantage of rodents’ exceptional olfactory abilities, the present study applied rigorous psychophysical techniques to the evaluation of discrimination learning in young and aged F344 rats. Aging did not influence odor detection thresholds or the ability to discriminate between perceptually distinct odorants. In contrast, aged rats were disproportionately impaired relative to young on problems that required discriminations between perceptually similar olfactory stimuli. Importantly, these disproportionate impairments in discrimination learning did not simply reflect a global learning impairment in aged rats, as they performed other types of difficult discriminations on par with young rats. Among aged rats, discrimination deficits were strongly associated with spatial learning deficits. These findings reveal a new, sensitive behavioral approach for elucidating the neural mechanisms of cognitive decline associated with normal aging.

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Aging-related changes in calcium-binding proteins in rat perirhinal cortex

Cited by 37 publications

References 93 publications

Layer V perirhinal cortical ensemble activity during object exploration: A comparison between young and aged rats

Layer V perirhinal cortical ensemble activity during object exploration: A comparison between young and aged rats

Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo

Interaction between age and perceptual similarity in olfactory discrimination learning in F344 rats: relationships with spatial learning

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