Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory

Abstract Introduction In recent year deterioration in cognitive, learning, and memory become one of the significant problems in human life. Hippocampus is a pivotal part of the brain’s limbic system which serves a critical role in memory, learning process and regulating the emotions. In most regions of the brain, neurons are generated only at specific periods of early development, and not born in the adulthood. In contrast, hippocampal neurons are generated throughout development and adult life. The hippocampal dentate gyrus was reported to be one of the few regions of the mammalian brain where neurogenesis continue to occur throughout adulthood. The neurogenesis in the dentate gyrus was thought to play an important role in hippocampus-dependent learning and memory. The hippocampal formation is composed of the hippocampus proper, the dentate gyrus and the subiculum. The hippocampus proper is the largest part and is subdivided into fields designated as Cornu Ammonis or Ammon’s horn (CA) from CA1 to CA4. Ammon's horn is continuous with the subiculum, which acts as the main output source of the hippocampal formation. Aim of the Study To study the postnatal development of the hippocampal formation. Materials and Methods Five male albino rats from the following postnatal ages day 1, week 1, week 2, week3 and week 4 were studied by histological, immunohistochemical, and morphometric methods. Results The general architecture of the hippocampus proper with its polymorphic, pyramidal, and molecular layers was present at day1, whereas the details of the adult structure appeared at week 2. In the dentate gyrus, distinct lamination appeared at week 1 and its maturation continued with the production of neurons at the interhilar zone that peaked at week 2. The number and density of pyramidal axons and dendrites increase by age. Astrocytes increased in size and staining affinity for glial filaments, and acquired a stellate shape with age. Furthermore, the number of granule cell layers increased concomitantly with the increase in thickness of the molecular and polymorphic layers of both the hippocampus proper and the dentate gyrus. Conclusion The important sequences of events in the growth and maturation of the hippocampal formation in male albino rat occurred in the first 2 postnatal weeks.

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The peptidergic antidementia drug cerebrolysin increases neurogenesis in the adult rat dentate gyrus and improves spatial learning and memory

Neurobiology of Aging ◽

10.1016/s0197-4580(00)82863-8 ◽

2000 ◽

Vol 21 ◽

pp. 42 ◽

Cited By ~ 2

Author(s):

Yoshitaka Tatebayashi ◽

Moon H. Lee ◽

Khalid Iqbal ◽

Inge Grundke-Iqbal

Keyword(s):

Dentate Gyrus ◽

Learning And Memory ◽

Spatial Learning ◽

Spatial Learning And Memory ◽

Adult Rat

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Chronic stress accelerates learning and memory impairments and increases amyloid deposition in APP V717I ‐CT100 transgenic mice, an Alzheimer's disease model

The FASEB Journal ◽

10.1096/fj.05-4265fje ◽

2006 ◽

Vol 20 (6) ◽

pp. 729-731 ◽

Cited By ~ 146

Author(s):

Yun Ha Jeong ◽

Cheol Hyoung Park ◽

Jongman Yoo ◽

Ki Young Shin ◽

Sung‐Min Ahn ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Learning And Memory ◽

Chronic Stress ◽

Disease Model ◽

Amyloid Deposition ◽

Memory Impairments

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Selective Modulation of Tonic and Phasic Inhibitions in Dentate Gyrus Granule Cells

Journal of Neurophysiology ◽

10.1152/jn.2002.87.5.2624 ◽

2002 ◽

Vol 87 (5) ◽

pp. 2624-2628 ◽

Cited By ~ 325

Author(s):

Zoltan Nusser ◽

Istvan Mody

Keyword(s):

Dentate Gyrus ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Hippocampal Slices ◽

Tonic Inhibition ◽

Adult Rats ◽

Adult Rat ◽

Phasic Inhibition ◽

The Mean

In some nerve cells, activation of GABAA receptors by GABA results in phasic and tonic conductances. Transient activation of synaptic receptors generates phasic inhibition, whereas tonic inhibition originates from GABA acting on extrasynaptic receptors, like in cerebellar granule cells, where it is thought to result from the activation of extrasynaptic GABAA receptors with a specific subunit composition (α6βxδ). Here we show that in adult rat hippocampal slices, extracellular GABA levels are sufficiently high to generate a powerful tonic inhibition in δ subunit–expressing dentate gyrus granule cells. In these cells, the mean tonic current is approximately four times larger than that produced by spontaneous synaptic currents occurring at a frequency of ∼10 Hz. Antagonizing the GABA transporter GAT-1 with NO-711 (2.5 μM) selectively enhanced tonic inhibition by 330% without affecting the phasic component. In contrast, by prolonging the decay of inhibitory postsynaptic currents (IPSCs), the benzodiazepine agonist zolpidem (0.5 μM) augmented phasic inhibition by 66%, while leaving the mean tonic conductance unchanged. These results demonstrate that a tonic GABAA receptor–mediated conductance can be recorded from dentate gyrus granule cells of adult rats in in vitro slice preparations. Furthermore, we have identified distinct pharmacological tools to selectively modify tonic and phasic inhibitions, allowing future studies to investigate their specific roles in neuronal function.

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Different effect of chronic stress on learning and memory in BALB/c and C57BL/6 inbred mice: Involvement of hippocampal NO production and PKC activity

Stress ◽

10.1080/10253890802506383 ◽

2009 ◽

Vol 12 (4) ◽

pp. 350-361 ◽

Cited By ~ 21

Author(s):

María Laura Palumbo ◽

María Aurelia Zorrilla Zubilete ◽

Graciela Alicia Cremaschi ◽

Ana María Genaro

Keyword(s):

Learning And Memory ◽

Chronic Stress ◽

Inbred Mice ◽

No Production

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Erratum: Corrigendum: Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model

Nature Communications ◽

10.1038/ncomms5810 ◽

2014 ◽

Vol 5 (1) ◽

Cited By ~ 6

Author(s):

Zheng Wu ◽

Ziyuan Guo ◽

Marla Gearing ◽

Gong Chen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dentate Gyrus ◽

Disease Model ◽

Long Term Potentiation ◽

Tonic Inhibition ◽

Term Potentiation

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Facilitation of the HPA Axis to a Novel Acute Stress Following Chronic Stress Exposure Modulates Histone Acetylation and the ERK/MAPK Pathway in the Dentate Gyrus of Male Rats

Endocrinology ◽

10.1210/en.2013-1918 ◽

2014 ◽

Vol 155 (8) ◽

pp. 2942-2952 ◽

Cited By ~ 21

Author(s):

Chantelle L. Ferland ◽

Erin P. Harris ◽

Mai Lam ◽

Laura A. Schrader

Keyword(s):

Dentate Gyrus ◽

Histone Acetylation ◽

Chronic Stress ◽

Hpa Axis ◽

Acute Stress ◽

Male Rats ◽

Stress Exposure ◽

Erk Activation ◽

Acute And Chronic Stress ◽

Acute Stressor

Evidence suggests that when presented with novel acute stress, animals previously exposed to chronic homotypic or heterotypic stressors exhibit normal or enhanced hypothalamic-pituitary-adrenal (HPA) response compared with animals exposed solely to that acute stressor. The molecular mechanisms involved in this effect remain unknown. The extracellular signal-regulated kinase (ERK) is one of the key pathways regulated in the hippocampus in both acute and chronic stress. The aim of this study was to examine the interaction of prior chronic stress, using the chronic variable stress model (CVS), with exposure to a novel acute stressor (2,5-dihydro-2,4,5-trimethyl thiazoline; TMT) on ERK activation, expression of the downstream protein BCL-2, and the glucocorticoid receptor co-chaperone BAG-1 in control and chronically stressed male rats. TMT exposure after chronic stress resulted in a significant interaction of chronic and acute stress in all 3 hippocampus subregions on ERK activation and BCL-2 expression. Significantly, acute stress increased ERK activation, BCL-2 and BAG-1 protein expression in the dentate gyrus (DG) of CVS-treated rats compared with control, CVS-treated alone, and TMT-only animals. Furthermore, CVS significantly increased ERK activation in medial prefrontal cortex, but acute stress had no significant effect. Inhibition of corticosterone synthesis with metyrapone had no significant effect on ERK activation in the hippocampus; therefore, glucocorticoids alone do not mediate the molecular effects. Finally, because post-translational modifications of histones are believed to play an important role in the stress response, we examined changes in histone acetylation. We found that, in general, chronic stress decreased K12H4 acetylation, whereas acute stress increased acetylation. These results indicate a molecular mechanism by which chronic stress-induced HPA axis plasticity can lead to neurochemical alterations in the hippocampus that influence reactivity to subsequent stress exposure. This may represent an important site of dysfunction that contributes to stress-induced pathology such as depression, anxiety disorders, and posttraumatic stress disorder.

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