DHEA potentiates the function of astrocytic glutamate transporter GLT-1 in the dentate gyrus of rat hippocampal slices

2009 ◽  
Vol 65 ◽  
pp. S86
Author(s):  
Motoki Tanaka ◽  
Ling Chen ◽  
Masahiro Sokabe
Keyword(s):  
Dentate Gyrus ◽  
Hippocampal Slices ◽  
Glutamate Transporter

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

2002 ◽  
Vol 87 (5) ◽  
pp. 2624-2628 ◽  
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.

scholarly journals Heterosynaptic NMDA Receptor Plasticity in Hippocampal Dentate Granule Cells

2022 ◽  
Author(s):  
Alma Rodenas-Ruano ◽  
Kaoutsar Nasrallah ◽  
Stefano Lutzu ◽  
Maryann Castillo ◽  
Pablo E. Castillo
Keyword(s):  
Dentate Gyrus ◽  
Entorhinal Cortex ◽  
Information Transfer ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Dentate Granule Cells ◽  
Hippocampus Proper ◽  
Receptor Plasticity ◽  
Activity Dependent

The dentate gyrus is a key relay station that controls information transfer from the entorhinal cortex to the hippocampus proper. This process heavily relies on dendritic integration by dentate granule cells (GCs) of excitatory synaptic inputs from medial and lateral entorhinal cortex via medial and lateral perforant paths (MPP and LPP, respectively). N-methyl-D-aspartate receptors (NMDARs) can contribute significantly to the integrative properties of neurons. While early studies reported that excitatory inputs from entorhinal cortex onto GCs can undergo activity-dependent long-term plasticity of NMDAR-mediated transmission, the input-specificity of this plasticity along the dendritic axis remains unknown. Here, we examined the NMDAR plasticity rules at MPP-GC and LPP-GC synapses using physiologically relevant patterns of stimulation in acute rat hippocampal slices. We found that MPP-GC, but not LPP-GC synapses, expressed homosynaptic NMDAR-LTP. In addition, induction of NMDAR-LTP at MPP-GC synapses heterosynaptically potentiated distal LPP-GC NMDAR plasticity. The same stimulation protocol induced homosynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-LTP at MPP-GC but heterosynaptic AMPAR-LTD at distal LPP synapses, demonstrating that NMDAR and AMPAR are governed by different plasticity rules. Remarkably, heterosynaptic but not homosynaptic NMDAR-LTP required Ca2+ release from intracellular, ryanodine-dependent Ca2+ stores. Lastly, the induction and maintenance of both homo- and heterosynaptic NMDAR-LTP were blocked by GluN2D antagonism, suggesting the recruitment of GluN2D-containing receptors to the synapse. Our findings uncover a mechanism by which distinct inputs to the dentate gyrus may interact functionally and contribute to hippocampal-dependent memory formation.

scholarly journals Chronic Unexpected Mild Stress Destroys Synaptic Plasticity of Neurons through a Glutamate Transporter, GLT-1, of Astrocytes in the Ischemic Stroke Rat

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Dafan Yu ◽  
Zhenxing Cheng ◽  
Abdoulaye Idriss Ali ◽  
Jiamin Wang ◽  
Kai Le ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Average Distance ◽  
Glutamate Transporter ◽  
Synaptic Cleft ◽  
Mild Stress ◽  
Poststroke Depression ◽  
Transmission Electron ◽  
Synaptic Formation

Background and Objective. Chronic unexpected mild stress (CUMS) destroys synaptic plasticity of hippocampal regenerated neurons that may be involved in the occurrence of poststroke depression. Astrocytes uptake glutamate at the synapse and provide metabolic support for neighboring neurons. Currently, we aim to investigate whether CUMS inhibits synaptic formation of regenerated neurons through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. Method. We exposed the ischemic stroke rats to ceftriaxone, during the CUMS intervention period to determine the effects of GLT-1 on glutamate circulation by immunofluorescence and mass spectrometry and its influences to synaptic plasticity by western blot and transmission electron microscopy. Result. CUMS evidently reduced the level of astroglial GLT-1 in the hippocampus of the ischemic rats (p<0.05), resulting in smaller amount of glutamate being transported into astrocytes surrounding synapses (p<0.05), and then expression of synaptophysin was suppressed (p<0.05) in hippocampal dentate gyrus. The ultrastructures of synapses in dentate gyrus were adversely influenced including decreased proportion of smile synapses, shortened thickness of postsynaptic density, reduced number of vesicles, and widened average distance of the synaptic cleft (all p<0.05). Moreover, ceftriaxone can promote glutamate circulation and synaptic plasticity (all p<0.05) by raising astroglial GLT-1 (p<0.05) and then improve depressive behaviors of the CUMS-induced model rats (p<0.05). Conclusion. Our study shows that CUMS destroys synaptic plasticity of regenerated neurons in the hippocampus through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. This may indicate one potential pathogenesis of poststroke depression.

The effects of midazolam on hippocampal dentate gyrus granule neurons from young and old Fischer 344 rats

1989 ◽  
Vol 67 (4) ◽  
pp. 359-362 ◽  
Author(s):  
J. N. Reynolds ◽  
P. L. Carlen
Keyword(s):  
Membrane Potential ◽  
Dentate Gyrus ◽  
Spike Train ◽  
Hippocampal Slices ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Granule Neurons ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Central Neurons

The effects of midazolam (3 nM) perfusion on the membrane and synaptic properties of dentate gyrus granule neurons were examined in hippocampal slices obtained from young adult (4–6 months) and old (24–26 months) Fischer 344 rats. In young neurons, midazolam perfusion resulted in a hyperpolarization of the resting membrane potential with no apparent change in the input resistance. Midazolam perfusion also produced a significant increase in the amplitude of the post-spike train afterhyperpolarization (AHP). In neurons obtained from old animals, midazolam perfusion also produced a hyperpolarization of the resting membrane potential but did not signficantly change the AHP. These effects may result from altered calcium homeostasis in neurons of the aged brain, and suggest that at least some of the direct actions of benzodiazepines on mammalian central neurons are altered during aging.Key words: aging, midazolam, hippocampus, dentate granule neuron, post-spike train afterhyperpolarization.

scholarly journals Enhanced Tonic GABA Current in Normotopic and Hilar Ectopic Dentate Granule Cells After Pilocarpine-Induced Status Epilepticus

2009 ◽  
Vol 102 (2) ◽  
pp. 670-681 ◽  
Author(s):  
Ren-Zhi Zhan ◽  
J. Victor Nadler
Keyword(s):  
Plasma Membrane ◽  
Status Epilepticus ◽  
Action Potential ◽  
Dentate Gyrus ◽  
Membrane Transport ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Gaba Concentration ◽  
Dentate Granule Cells ◽  
Gaba Inhibition

In temporal lobe epilepsy, loss of inhibitory neurons and circuit changes in the dentate gyrus promote hyperexcitability. This hyperexcitability is compensated to the point that dentate granule cells exhibit normal or even subnormal excitability under some conditions. This study explored the possibility that compensation involves enhanced tonic GABA inhibition. Whole cell patch-clamp recordings were made from normotopic granule cells in hippocampal slices from control rats and from both normotopic and hilar ectopic granule cells in slices from rats subjected to pilocarpine-induced status epilepticus. After status epilepticus, tonic GABA current was an order of magnitude greater than control in normotopic granule cells and was significantly greater in hilar ectopic than in normotopic granule cells. These differences could be observed whether or not the extracellular GABA concentration was increased by adding GABA to the superfusion medium or blocking plasma membrane transport. The enhanced tonic GABA current had both action potential–dependent and action potential–independent components. Pharmacological studies suggested that the small tonic GABA current of granule cells in control rats was mediated largely by high-affinity α4βxδ GABAA receptors but that the much larger current recorded after status epilepticus was mediated largely by the lower-affinity α5βxγ2 GABAA receptors. A large α5βxγ2-mediated tonic current could be recorded from controls only when the extracellular GABA concentration was increased. Status epilepticus seemed not to impair the control of extracellular GABA concentration by plasma membrane transport substantially. Upregulated tonic GABA inhibition may account for the unexpectedly modest excitability of the dentate gyrus in epileptic brain.

scholarly journals Lesion-Induced Alterations in Astrocyte Glutamate Transporter Expression and Function in the Hippocampus

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Alexandra E. Schreiner ◽  
Eric Berlinger ◽  
Julia Langer ◽  
Karl W. Kafitz ◽  
Christine R. Rose
Keyword(s):  
Cell Damage ◽  
Glutamate Uptake ◽  
Hippocampal Slices ◽  
Glutamate Transporter ◽  
Reactive Astrocytes ◽  
Extracellular Glutamate ◽  
Sodium Imaging ◽  
Ca1 Area ◽  
And Function ◽  
Transporter Expression

Astrocytes express the sodium-dependent glutamate transporters GLAST and GLT-1, which are critical to maintain low extracellular glutamate concentrations. Here, we analyzed changes in their expression and function following a mechanical lesion in the CA1 area of organotypic hippocampal slices. 6-7 days after lesion, a glial scar had formed along the injury site, containing strongly activated astrocytes with increased GFAP and S100β immunoreactivity, enlarged somata, and reduced capability for uptake of SR101. Astrocytes in the scar’s periphery were swollen as well, but showed only moderate upregulation of GFAP and S100β and efficiently took up SR101. In the scar, clusters of GLT-1 and GLAST immunoreactivity colocalized with GFAP-positive fibers. Apart from these, GLT-1 immunoreactivity declined with increasing distance from the scar, whereas GLAST expression appeared largely uniform. Sodium imaging in reactive astrocytes indicated that glutamate uptake was strongly reduced in the scar but maintained in the periphery. Our results thus show that moderately reactive astrocytes in the lesion periphery maintain overall glutamate transporter expression and function. Strongly reactive astrocytes in the scar, however, display clusters of GLAST and GLT-1 immunoreactivity together with reduced glutamate transport activity. This reduction might contribute to increased extracellular glutamate concentrations and promote excitotoxic cell damage at the lesion site.

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