Reduced hippocampal CA1 Ca2+-induced long-term potentiation is associated with age-dependent impairment of spatial learning

Diana, Giovanni; Domenici, Maria Rosaria; Carolis, A. Scotti de; Loizzo, Alberto; Sagratella, S.

doi:10.1016/0006-8993(95)00440-2

Cited by 41 publications

(24 citation statements)

References 14 publications

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“…The finding that vehicle-treated aged rats failed to exhibit a differential search strategy on the retention probe trial is similar to previous reports that have observed rapid forgetting in aged animals (e.g. Barnes & McNaughton, 1985;Diana et al, 1995;Rasmussen et al, 1996;Foster et al, 1991;Gage et al, 1984;Gold, McGaugh, Hankins, Rose, & Vasquez, 1981;Linder, Balch, & VanderMaelen, 1992;Mabry et al, 1996;Rapp et al, 1987;Winocur, 1988). Secondly, when the number of platform crossings was examined for both probe trials (Tables 1 and 2), each group except the aged MK-801 rats exhibited a drop in the number of crossings from the acquisition probe to the retention probe, indicating that aged rats injected with MK-801 continued to focus their search to the location that had contained the platform.…”

Section: Figsupporting

confidence: 90%

“…Of particular sensitivity to the aging process are behaviors that depend on the integrity of the hippocampus, such as spatial navigation (Geinisman, deToledo-Morrell, Morrell, & Heller, 1995). Deficits in spatial cognition are consistently observed in aged rodents performing the Morris swim task (Diana, Domenici, de Carolis, Loizzo, & Sagratella, 1995;Rasmussen, Schliemann, Sorensen, Zimmer, & West, 1996;Foster, Barnes, Rao, & McNaughton, 1991;Gage, Dunnett, & Bjorklund, 1984;Mabry, McCarty, Gold, & Foster, 1996;Rapp, Rosenberg, & Gallagher, 1987). A general finding is that aged individuals exhibit more rapid forgetting over an extended period of time relative to adults.…”

Section: Introductionmentioning

confidence: 99%

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MK-801 Improves Retention in Aged Rats: Implications for Altered Neural Plasticity in Age-Related Memory Deficits

Norris

Foster

1999

Neurobiology of Learning and Memory

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Alterations in N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity, characteristic of aged rodents, may contribute to impaired memory with advanced age. The purpose of the current research was to examine whether NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22-24 months) and adult (3-6 months) male Fischer 344 rats received 18 training trials, over a period of 3 to 4 h, on the spatial version of the Morris water maze. Immediately after training, a standard free-swim probe trial was administered to assess the acquisition of spatial bias, which was determined by the percent of time spent in the goal quadrant and the number of platform crossings. Rats then received injections of the noncompetitive NMDAR antagonist, (ϩ)-10,11-dihydro-5methyl-5H-dibenzo-(a,b)cycloheptene-5,10 imine (MK-801, 0.05 mg/kg, i.p.), or a vehicle injection of equal volume. Approximately 24 h later, rats were administered a second free-swim probe trial to assess retention of spatial bias. All age/drug groups exhibited a spatial bias on the acquisition probe, with adults generally outperforming the aged rats. On the retention probe, this spatial bias continued to be shown by adult rats, regardless of treatment. For the aged group, in contrast, only MK-801-injected rats maintained a spatial bias on the retention probe, suggesting that NMDAR activity may be involved in rapid forgetting during aging. Because blockade of NMDARs also may impair new learning, which may, in turn, protect previously stored information from retroactive interference, rats in a second experiment received post-training injections of scopolamine (0.05 mg/kg), a compound known to inhibit learning. However, scopolamine did not enhance retention in the aged group, consistent with the hypothesis that MK-801 influenced memory in aged rats through its actions on NMDAR-dependent synaptic plasticity.

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Section: Figsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

MK-801 Improves Retention in Aged Rats: Implications for Altered Neural Plasticity in Age-Related Memory Deficits

Norris

Foster

1999

Neurobiology of Learning and Memory

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“…When training is distributed across days, some aged rats exhibit a characteristic "saw-toothed" pattern of behavior which appears as an improved performance for training trials within a day, and a marked decrement in performance on the first trial of the next day (Diana et al 1995;Gage et al 1984;Rapp et al 1987). With continued training aged animals improve to a level comparable to that observed in younger animals (Rapp et al 1987), however; in some cases aged animals continue to exhibit deficits, such that aged animals can be categorized as learning impaired and unimpaired.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats

Foster

Kumar

2007

Neurobiology of Learning and Memory

107

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The current study employed aged and young male Fischer 344 rats to examine the relationship between long-term depression (LTD), age, and memory. Memory performance was measured on two tasks that are sensitive to hippocampal function; inhibitory avoidance and spatial discrimination on the Morris water maze. The slope of the extracellular excitatory postsynaptic field potential was recorded from CA3-CA1 synapses in hippocampal slices. Low frequency stimulation (LFS) induced a modest LTD only in aged animals under standard recording conditions. The decrease in synaptic transmission examined only in aged animals correlated with memory scores on the spatial task and LTD was not observed in aged animals with the highest memory scores. LTD induction was facilitated by increasing the Ca 2+ /Mg 2+ ratio of the recording medium or employing a paired-pulse stimulation paradigm. Age differences disappeared when LFS was delivered under conditions of elevated Ca 2+ /Mg 2+ in the recording medium. Using multiple induction episodes under conditions which facilitate LTD-induction, no age-related difference was observed in the maximum level of LTD. The results indicate that the increased susceptibility to LTD induction is associated with impaired memory and results from a shift in the induction process. The possible relationship between LTD and memory function is discussed.

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“…One particular age-related impairment in neuronal function in the rat is a decrease in ability to sustain long term potentiation (LTP 1 ; Refs. [1][2][3][4][5], which is a putative biological substrate for cognitive function and a model for learning and/or memory. Evidence suggests that a cascade of biochemical changes, initiated by activation of the N-methyl-D-aspartate subtype of glutamate receptor is required to support this form of synaptic plasticity in the dentate gyrus (6).…”

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confidence: 99%

Dietary Supplementation with Vitamin E Reverses the Age-related Deficit in Long Term Potentiation in Dentate Gyrus

Murray

Lynch

1998

Journal of Biological Chemistry

145

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Long term potentiation (LTP) in dentate gyrus is impaired in aged rats, and this has been associated with an age-related decrease in membrane arachidonic acid concentration. In this study, we considered whether the trigger for this age-related decrease in arachidonic acid might be increased lipid peroxidation stimulated by the proinflammatory cytokine, interleukin-1␤. Groups of aged and young rats were fed on a control diet or a diet supplemented with ␣-tocopherol and assessed for their ability to sustain LTP. Aged rats fed on the control diet exhibited an impaired ability to sustain LTP and analysis of tissue prepared from these rats exhibited increased interleukin-1␤, increased lipid peroxidation, and decreased membrane arachidonic acid concentration compared with young rats fed on either diet. Aged rats fed on the supplemented diet sustained LTP in a manner indistinguishable from young rats, and the agerelated increases in interleukin-1␤ and lipid peroxidation and the decrease in membrane arachidonic acid concentration were all reversed. We propose that interleukin-1␤ may be the trigger that induces these agerelated changes and may therefore be responsible for the deficit in long term potentiation in aged rats. The observation that ␣-tocopherol reverses these changes is consistent with the hypothesis that some age-related changes in hippocampus might derive from oxidative stress.Aging is associated with compromised neuronal activity, perhaps typified by a deficit in cognitive function. One particular age-related impairment in neuronal function in the rat is a decrease in ability to sustain long term potentiation (LTP 1 ; Refs. 1-5), which is a putative biological substrate for cognitive function and a model for learning and/or memory. Evidence suggests that a cascade of biochemical changes, initiated by activation of the N-methyl-D-aspartate subtype of glutamate receptor is required to support this form of synaptic plasticity in the dentate gyrus (6). Although the underlying cause of the age-related impairment in ability to sustain LTP is not known, down-regulation of several components of the biochemical cascade has been identified in aged rats. Thus, N-methyl-D-aspartate receptor activity is compromised with age (e.g. Ref. 7), whereas down-regulation of other factors that play a role in induction of LTP, like calcium handling by cells (1) and activation of enzymes such as phospholipase A 2 (3) and protein kinases (8), has been reported. Similarly, factors that play a role in maintenance of LTP, like increased glutamate release, have also been shown to be compromised in hippocampus of aged rats (3,5,9). In addition, the more persistent aspects of LTP, which rely on increased synthesis of new proteins (10 -12) and morphological changes (13), are also impaired in the hippocampus of aged rats (12,14). Despite this immense body of data, the underlying cause of the impairment in ability of aged rats to sustain LTP is not known.One unifying cause of the age-related changes in biochemical parameters might be a chan...

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Reduced hippocampal CA1 Ca2+-induced long-term potentiation is associated with age-dependent impairment of spatial learning

Cited by 41 publications

References 14 publications

MK-801 Improves Retention in Aged Rats: Implications for Altered Neural Plasticity in Age-Related Memory Deficits

MK-801 Improves Retention in Aged Rats: Implications for Altered Neural Plasticity in Age-Related Memory Deficits

Susceptibility to induction of long-term depression is associated with impaired memory in aged Fischer 344 rats

Dietary Supplementation with Vitamin E Reverses the Age-related Deficit in Long Term Potentiation in Dentate Gyrus

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