Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

Kumar, Ashok

doi:10.3389/fnagi.2011.00007

Cited by 133 publications

(102 citation statements)

References 523 publications

(671 reference statements)

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“…Interestingly, this effect was seen for both up-and downregulated genes ( Figure 1I). Functional enrichment analysis showed that age-associated increases in gene expression were linked to inflammatory processes, while decreases represented pathways linked to metabolism and transcriptional response ( Figure 1J Interestingly, we did not find any pathways linked to synaptic plasticity, which is known to decrease in the aging brain (23). These data suggest that the impact of aging on gene expression and the effect of SAHA are likely to be complex.…”

Section: Introductionmentioning

confidence: 52%

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

Benito

Urbanke

Ramachandran

et al. 2015

Journal of Clinical Investigation

161

137

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Section: Introductionmentioning

confidence: 52%

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

Benito

Urbanke

Ramachandran

et al. 2015

Journal of Clinical Investigation

161

137

View full text Add to dashboard Cite

show abstract

“…It has been reported that long-term potentiation (LTP), a form of synaptic plasticity characterized by a persistent increase in excitatory synaptic strength and regarded as a potential cellular model of learning (Kumar, 2011), is enhanced in the Schaffer collateral-CA1 synapses of the mSOD1 mouse hippocampus (Spalloni et al, 2006). From these data it was inferred that presymptomatic mSOD1 mice have an enhancement of hippocampal functionality that provides favorable conditions for spatial information processing.…”

Section: Discussionmentioning

confidence: 74%

Increased anxiety‐like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model

Quarta

Bravi

Scambi

et al. 2015

J of Comparative Neurology

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Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease primarily characterized by motor neuron death, causes damages beyond motor-related areas. In particular, cognitive impairments and hippocampal damage have been reported in ALS patients. We investigated spatial navigation learning and hippocampal interneurons in a mutant SOD1(G93A) mouse (mSOD1) model of ALS. Behavioral tests were performed by using presymptomatic mSOD1 mice. General motor activity was comparable to that of wild-type mice in the open-field test, in which, however mSOD1 exhibited increased anxiety-like behavior. In the Barnes maze test, mSOD1 mice displayed a delay in learning, outperformed wild-type mice during the first probe trial, and exhibited impaired long-term memory. Stereological counts of parvalbumin-positive interneurons, which are crucial for hippocampal physiology and known to be altered in other central nervous system regions of mSOD1 mice, were also performed. At postnatal day (P) 56, the population of parvalbumin-positive interneurons in mSOD1 mice was already reduced in CA1 and in CA3, and at P90 the reduction extended to the dentate gyrus. Loss of parvalbumin-positive hippocampal interneurons occurred mostly during the presymptomatic stage. Western blot analysis showed that hippocampal parvalbumin expression levels were already reduced in mSOD1 mice at P56. The hippocampal alterations in mSOD1 mice could at least partly account for the increased anxiety-like behavior and deficits in spatial navigation learning. Our study provides evidence for cognitive alterations and damage to the γ-aminobutyric acid (GABA)ergic system in the hippocampus of murine ALS, thereby revealing selective deficits antecedent to the onset of motor symptoms.

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“…There is voluminous evidence that deficient NMDAR‐dependent LTP results in learning and memory impairments (David Sweatt, 2009) and that hippocampal LTP declines with age (Lynch, 2010; Kumar, 2011). Moreover, the rapid recruitment of NMDA receptor subunits can reduce the threshold for LTP, a process that appears to be dependent on dendritic mRNA translation (Swanger et al ., 2013).…”

Section: Discussionmentioning

confidence: 99%

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

et al. 2016

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SummaryHippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age‐associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR‐204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR‐204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR‐204 also decreased the total expression of NR1. miR‐204 induces senescence‐like phenotype in fully matured neurons as evidenced by an increase in p16‐positive cells. We suggest that aging is accompanied by the upregulation of miR‐204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age‐associated decline in hippocampal synaptic plasticity and the related cognitive functions.

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Long-Term Potentiation at CA3–CA1 Hippocampal Synapses with Special Emphasis on Aging, Disease, and Stress

Cited by 133 publications

References 523 publications

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

HDAC inhibitor–dependent transcriptome and memory reinstatement in cognitive decline models

Increased anxiety‐like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

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