Increased Susceptibility to Induction of Long-Term Depression and Long-Term Potentiation Reversal during Aging

Norris, Christopher M.; Korol, Donna L.; Foster, Thomas C.

doi:10.1523/jneurosci.16-17-05382.1996

Cited by 267 publications

(274 citation statements)

References 45 publications

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“…However, chronic recording studies led to the important discovery that LTP in the perforant path projections to the dentate gyrus decays more quickly in the aged brain (Barnes, 1979). Subsequent work with slices identified deficits in the induction and/or expression of LTP in field CA1 (Deupree et al, 1993;Sankar et al, 2000) while others, in agreement with the earlier studies, found no evidence for deficits in that region (Diana et al, 1994;Norris et al, 1996). It now appears that these discrepancies depend on the stimulation patterns used to induce potentiation (Moore et al, 1993;Lanahan et al, 1997;Watabe and O'Dell, 2003) and the extent to which the animals have learning problems (Tombaugh et al, 2002).…”

Section: Plasticity In Old Agementioning

confidence: 69%

Synaptic plasticity in early aging

Lynch

Rex

Gall

2006

Ageing Research Reviews

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Studies of how aging affects brain plasticity have largely focused on old animals. However, deterioration of memory begins well in advance of old age in animals, including humans; the present review is concerned with the possibility that changes in synaptic plasticity, as found in the long-term potentiation (LTP) effect, are responsible for this. Recent results indicate that impairments to LTP are in fact present by early middle age in rats but only in certain dendritic domains. The search for the origins of these early aging effects necessarily involves ongoing analyses of how LTP is induced, expressed, and stabilized. Such work points to the conclusion that cellular mechanisms responsible for LTP are redundant and modulated both positively and negatively by factors released during induction of potentiation. Tests for causes of the localized failure of LTP during early aging suggest that the problem lies in excessive activity of a negative modulator. The view of LTP as having redundant and modulated substrates also suggests a number of approaches for reversing age-related losses. Particular attention will be given to the idea that induction of brain-derived neurotrophic factor, an extremely potent positive modulator, can be used to provide long periods of normal plasticity with very brief pharmacological interventions. The review concludes with a consideration of how the selective, regional deficits in LTP found in early middle age might be related to the global phenomenon of brain aging. #

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Section: Plasticity In Old Agementioning

confidence: 69%

Synaptic plasticity in early aging

Lynch

Rex

Gall

2006

Ageing Research Reviews

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“…Substantial alteration of NMDA-receptor-mediated LTD has also been observed. In one study, NMDA-receptor-dependent LTD was enhanced in aged CA1 [70], whereas another recent study reported a pronounced reduction [69]. These discrepant results might be due to differences in strains of animals or methodological differences.…”

Section: Weakened Synaptic Plasticitymentioning

confidence: 89%

Neurocognitive aging: prior memories hinder new hippocampal encoding

Wilson

Gallagher

Eichenbaum

et al. 2006

Trends in Neurosciences

299

327

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Normal aging is often accompanied by impairments in forming new memories, and studies of aging rodents have revealed structural and functional changes to the hippocampus that might point to the mechanisms behind such memory loss. In this article, we synthesize recent neurobiological and neurophysiological findings into a model of the information-processing circuit of the aging hippocampus. The key point of the model is that small concurrent changes during aging strengthen the auto-associative network of the CA3 subregion at the cost of processing new information coming in from the entorhinal cortex. As a result of such reorganization in aged memory-impaired individuals, information that is already stored would become the dominant pattern of the hippocampus to the detriment of the ability to encode new information.

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“…Controversy exists on the effects of development and ageing on LTD. During maturation, induction of LTD is increasingly difficult [30±33]. Some authors report, however, a shift towards facilitation of LTD induction at advanced age [34].…”

Section: Discussionmentioning

confidence: 99%

“…This disturbed Ca 2+ homeostasis could be involved in the plasticity deficits observed, as LTP and LTD are calcium-dependent processes and the balance between LTP and LTD induction seems to be modulated by intracellular Ca 2+ concentrations [8,9]. In experimental models for ageing, as well as in models for diabetes, hippocampal synapses show plasticity modifications favouring LTD induction [11,34,44], whereas LTP expression and maintenance is impaired [11,45]. In ageing rats, it was shown that an increase in Ca 2+ influx through L-type voltagedependent Ca 2+ channels can lower the LTD induction threshold [26].…”

Section: Discussionmentioning

confidence: 99%

Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing

et al. 2000

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Peripheral neuropathy is a well-known complication of both clinical and experimental diabetes mellitus. Long-term diabetes also leads to a variety of discrete functional and structural disorders in the central nervous system [1]. Moderate impairment of cognitive function has been observed in middle-aged adults with Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. In the elderly cognitive deficits appear, however, to be more pronounced and can readily be detected with relatively crude tests such as the mini-mental state examination [4,5].The hippocampus is a brain structure involved in certain forms of learning [6,7]. At the cellular level, hippocampal long-term potentiation (LTP) and depression (LTD) are two forms of synaptic plasticity which have attracted considerable attention in the search for the mechanisms of learning and memory [8,9]. We have shown previously that LTP expression was impaired in the CA1 and the CA3 field of the hippocampus of young adult diabetic rats, whereas LTD expression in the CA1 field was enhanced [10, Diabetologia (2000) Abstract Aims/hypothesis. Diabetes mellitus leads to functional and structural changes in the brain which appear to be most pronounced in the elderly. Because the pathogenesis of brain ageing and that of diabetic complications show close analogies, it is hypothesized that the effects of diabetes and ageing on the brain interact. Our study examined the effects of diabetes and ageing on learning and hippocampal synaptic plasticity in rats. Methods. Young adult (5 months) and aged (2 years) rats were examined after 8 weeks of streptozotocindiabetes. Learning was tested in a Morris water maze. Synaptic plasticity was tested ex vivo, in hippocampal slices, in response to trains of stimuli of different frequency (0.05 to 100 Hz). Results. Statiscally significant learning impairments were observed in young adult diabetic rats compared with controls. These impairments were even greater in aged diabetic animals. In hippocampal slices from young adult diabetic animals long-term potentiation induced by 100 Hz stimulation was impaired compared with controls (138 vs 218 % of baseline). In contrast, long-term depression induced by 1 Hz stimulation was enhanced in slices from diabetic rats compared with controls (79 vs 92 %). In non-diabetic aged rats synaptic responses were 149 and 93 % of baseline in response to 100 and 1 Hz stimulation, compared with 106 and 75 % in aged diabetic rats. Conclusion/interpretation. Both diabetes and ageing affect learning and hippocampal synaptic plasticity. The cumulative deficits in learning and synaptic plasticity in aged diabetic rats indicate that the effects of diabetes and ageing on the brain could interact. [Diabetologia (2000) 43: 500±506]

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Increased Susceptibility to Induction of Long-Term Depression and Long-Term Potentiation Reversal during Aging

Cited by 267 publications

References 45 publications

Synaptic plasticity in early aging

Synaptic plasticity in early aging

Neurocognitive aging: prior memories hinder new hippocampal encoding

Learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: interaction of diabetes and ageing

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