Stress-Induced Memory Retrieval Impairments: Different Time-Course Involvement of Corticosterone and Glucocorticoid Receptors in Dorsal and Ventral Hippocampus

Prolonged stress results in elevation of glucocorticoid (GC) hormones, which can have deleterious effects in the brain. The hippocampus, which has a high concentration of glucocorticoid receptors, is especially vulnerable to increasing levels of GCs. GCs have been suggested to endanger hippocampal neurons by exacerbating the excitotoxic glutamate–calcium–reactive oxygen species (ROS) cascade. In an effort to reveal the mechanisms underlying GC-mediated hippocampal neurotoxicity, we aimed to clarify the molecular pathway of GC-induced ROS increase by using organotypic hippocampal slice cultures. Assays for ROS, using 2′,7′-dichlorodihydrofluorescein diacetate fluorescence, showed that treatment of synthetic GC, dexamethasone (DEX) significantly enhanced ROS levels. Time course and dose response analyses indicated that peak amount of ROS was generated at 4 h after treatment with 50 µmol/L DEX. By contrast, other steroid hormones, progesterone and estradiol did not influence ROS production. N-acetyl-l-cysteine completely suppressed ROS produced by DEX. Propidium iodide staining exhibited prominent cell death in the hippocampal layer after 96 h of DEX treatment. RU486, a GC receptor antagonist, almost completely blocked the effect of DEX on ROS production and cell death, indicating that DEX-induced ROS overproduction and hippocampal death are mediated via GC receptors. Real-time reverse transcriptase PCR analysis demonstrated that after DEX treatment the level of glutathione peroxidase mRNA was decreased whereas that of NADPH oxidase mRNA was significantly enhanced. These findings suggest that excess GCs cause hippocampal damage by regulating genes involved in ROS generation.

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The Timing of Lexical Memory Retrievals in Language Production

10.31234/osf.io/tmxdf ◽

2017 ◽

Author(s):

Jeremy Cole ◽

David Reitter

Keyword(s):

Memory Retrieval ◽

Language Production ◽

Large Scale ◽

Time Course ◽

Computational Analysis ◽

Cognitive Architecture ◽

Lexical Memory ◽

Lexical Information ◽

Time Point ◽

Fluent Language

This paper explores the time course of lexical memory retrieval by modeling fluent language production. The duration of retrievals is predicted using the ACT-R cognitive architecture. In a large-scale observational study of a spoken corpus, we find that language production at a time point preceding a word is sped up or slowed down depending on activation of that word. This computational analysis has consequences for the theoretical model of language production. The data point to interference between lexical and phonological stages as well as a quantifiable buffer for lexical information.

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Alpha-band oscillations track the retrieval of precise spatial representations from long-term memory

Journal of Neurophysiology ◽

10.1152/jn.00268.2019 ◽

2019 ◽

Vol 122 (2) ◽

pp. 539-551 ◽

Cited By ~ 3

Author(s):

David W. Sutterer ◽

Joshua J. Foster ◽

John T. Serences ◽

Edward K. Vogel ◽

Edward Awh

Keyword(s):

Memory Retrieval ◽

Time Course ◽

Brain Activity ◽

Initial Study ◽

Long Term Memory ◽

Spatial Representations ◽

Alpha Band ◽

Term Memory ◽

Spatial Memories

A hallmark of episodic memory is the phenomenon of mentally reexperiencing the details of past events, and a well-established concept is that the neuronal activity that mediates encoding is reinstated at retrieval. Evidence for reinstatement has come from multiple modalities, including functional magnetic resonance imaging and electroencephalography (EEG). These EEG studies have shed light on the time course of reinstatement but have been limited to distinguishing between a few categories. The goal of this work was to use recently developed experimental and technical approaches, namely continuous report tasks and inverted encoding models, to determine which frequencies of oscillatory brain activity support the retrieval of precise spatial memories. In experiment 1, we establish that an inverted encoding model applied to multivariate alpha topography tracks the retrieval of precise spatial memories. In experiment 2, we demonstrate that the frequencies and patterns of multivariate activity at study are similar to the frequencies and patterns observed during retrieval. These findings highlight the broad potential for using encoding models to characterize long-term memory retrieval. NEW & NOTEWORTHY Previous EEG work has shown that category-level information observed during encoding is recapitulated during memory retrieval, but studies with this time-resolved method have not demonstrated the reinstatement of feature-specific patterns of neural activity during retrieval. Here we show that EEG alpha-band activity tracks the retrieval of spatial representations from long-term memory. Moreover, we find considerable overlap between the frequencies and patterns of activity that track spatial memories during initial study and at retrieval.

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Regulation of branched-chain ketoacid dehydrogenase flux by extracellular pH and glucocorticoids

AJP Cell Physiology ◽

10.1152/ajpcell.1997.272.6.c2031 ◽

1997 ◽

Vol 272 (6) ◽

pp. C2031-C2036 ◽

Cited By ~ 13

Author(s):

X. Wang ◽

C. Jurkovitz ◽

S. R. Price

Keyword(s):

Metabolic Acidosis ◽

Time Course ◽

Glucocorticoid Receptors ◽

Cell Types ◽

Extracellular Ph ◽

Total Flux ◽

Leucine Catabolism ◽

Branched Chain ◽

Ketoacid Dehydrogenase ◽

In Cells

In muscles of rats with metabolic acidosis, branched-chain alpha-ketoacid dehydrogenase (BCKAD) activity is increased. Potential stimulatory signals include acidemia and/or glucocorticoids. It is unclear whether the signal(s) increases BCKAD activity by changing the activation state of the enzyme or by increasing the amount of enzyme. To separate the influences of extracellular pH and glucocorticoids on leucine catabolism, maximal BCKAD flux and the activation state (the ratio of basal to total flux) were measured in two cell types: 1) cells that do not express glucocorticoid receptors and 2) cells stably transfected to express glucocorticoid receptors. Acidification (pH 6.95) increased 1) the activation state from 67.2% at pH 7.4 to 82.8% at pH 6.95, 2) maximal BCKAD flux by 50%, and 3) the BCKAD subunit contents in both cell types (57, 410, and 270% for E2, E1 alpha, and E1 beta, respectively). Dexamethasone increased the BCKAD activation state from 67.2 to 82.3% in cells expressing glucocorticoid receptors, whereas dexamethasone plus acidification increased the activation state to 98%. The time course of stimulation by dexamethasone was slower than that by acidification. These results demonstrate that BCKAD is differentially regulated by extracellular pH and glucocorticoids.

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