scholarly journals P2-073: ROLE OF GIRK CHANNELS IN LONG-TERM POTENTIATION OF SYNAPTIC INHIBITION IN AN IN VIVO MODEL OF EARLY AMYLOID-β PATHOLOGY

2019 ◽  
Vol 15 ◽  
pp. P599-P599
Author(s):  
Irene Sanchez-Rodriguez ◽  
Agnès Gruat ◽  
Jose Maria Delgado-Garcia ◽  
Lydia Jimenez-Diaz ◽  
Juan D. Navarro-Lopez
Keyword(s):  
Amyloid Β ◽  
Long Term Potentiation ◽  
In Vivo Model ◽  
Synaptic Inhibition ◽  
Girk Channels ◽  
Term Potentiation

scholarly journals Role of GirK Channels in Long-Term Potentiation of Synaptic Inhibition in an In Vivo Mouse Model of Early Amyloid-β Pathology

2019 ◽  
Vol 20 (5) ◽  
pp. 1168 ◽  
Author(s):  
Irene Sánchez-Rodríguez ◽  
Agnès Gruart ◽  
José Delgado-García ◽  
Lydia Jiménez-Díaz ◽  
Juan Navarro-López
Keyword(s):  
Mouse Model ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Synaptic Inhibition ◽  
Girk Channels ◽  
Girk Channel ◽  
Term Potentiation ◽  
Inhibitory Signaling

Imbalances of excitatory/inhibitory synaptic transmission occur early in the pathogenesis of Alzheimer’s disease (AD), leading to hippocampal hyperexcitability and causing synaptic, network, and cognitive dysfunctions. G-protein-gated potassium (GirK) channels play a key role in the control of neuronal excitability, contributing to inhibitory signaling. Here, we evaluate the relationship between GirK channel activity and inhibitory hippocampal functionality in vivo. In a non-transgenic mouse model of AD, field postsynaptic potentials (fPSPs) from the CA3–CA1 synapse in the dorsal hippocampus were recorded in freely moving mice. Intracerebroventricular (ICV) injections of amyloid-β (Aβ) or GirK channel modulators impaired ionotropic (GABAA-mediated fPSPs) and metabotropic (GirK-mediated fPSPs) inhibitory signaling and disrupted the potentiation of synaptic inhibition. However, the activation of GirK channels prevented Aβ-induced changes in GABAA components. Our data shows, for the first time, the presence of long-term potentiation (LTP) for both the GABAA and GirK-mediated inhibitory postsynaptic responses in vivo. In addition, our results support the importance of an accurate level of GirK-dependent signaling for dorsal hippocampal performance in early amyloid pathology models by controlling the excess of excitation that disrupts synaptic plasticity processes.

Amyloid-β oligomers: their production, toxicity and therapeutic inhibition

2002 ◽  
Vol 30 (4) ◽  
pp. 552-557 ◽  
Author(s):  
D. M. Walsh ◽  
I. Klyubin ◽  
J. V. Fadeeva ◽  
M. J. Rowan ◽  
D. J. Selkoe
Keyword(s):  
Amyloid Β ◽  
Long Term Potentiation ◽  
Specific Form ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Term Potentiation ◽  
Modelling Data

Despite extensive genetic and animal modelling data that support a central role for the amyloid β-protein (Aβ) in the genesis of Alzheimer's disease, the specific form(s) of Aβ which causes injury to neurons in vivo has not been identified. In the present study, we examine the importance of soluble, pre-fibrillar assemblies of Aβ as mediators of neurotoxicity. Specifically, we review the role of cell-derived SDS-stable oligomers, their blocking of hippocampal long-term potentiation in vivo and the finding that this blocking can be prevented by prior treatment of oligomer-producing cells withγ-secretase inhibitors.

Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo

Nature ◽  
2002 ◽  
Vol 416 (6880) ◽  
pp. 535-539 ◽  
Author(s):  
Dominic M. Walsh ◽  
Igor Klyubin ◽  
Julia V. Fadeeva ◽  
William K. Cullen ◽  
Roger Anwyl ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Long Term Potentiation ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Term Potentiation

scholarly journals Learning-induced modulation of the effect of neuroglial transmission on synaptic plasticity

2018 ◽  
Vol 119 (6) ◽  
pp. 2373-2379 ◽  
Author(s):  
Luna Jammal ◽  
Ben Whalley ◽  
Edi Barkai
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Piriform Cortex ◽  
Rule Learning ◽  
Long Term Potentiation ◽  
Synaptic Inhibition ◽  
Term Potentiation ◽  
Term Maintenance

Training rats in a complex olfactory discrimination task results in acquisition of “rule learning” (learning how to learn), a term describing the capability to perform the task superbly. Such rule learning results in strengthening of both excitatory and inhibitory synaptic connections between neurons in the piriform cortex. Moreover, intrinsic excitability is also enhanced throughout the pyramidal neuron population. Surprisingly, the cortical network retains its stability under these long-term modifications. In particular, the susceptibility for long-term potentiation (LTP) induction, while decreased for a short time window, returns to almost its pretraining value, although significant strengthening of AMPA receptor-mediated glutamatergic transmission remains. Such network balance is essential for maintaining the single-cell modifications that underlie long-term memory while preventing hyperexcitability that would result in runaway synaptic activity. However, the mechanisms underlying the long-term maintenance of such balance have yet to be described. In this study, we explored the role of astrocyte-mediated gliotransmission in long-term maintenance of learning-induced modifications in susceptibility for LTP induction and control of the strength of synaptic inhibition. We show that blocking connexin 43 hemichannels, which form gap junctions between astrocytes, decreases significantly the ability to induce LTP by stimulating the excitatory connections between piriform cortex pyramidal neurons after learning only. In parallel, spontaneous miniature inhibitory postsynaptic current amplitude is reduced in neurons from trained rats only, to the level of prelearning. Thus gliotransmission has a key role in maintaining learning-induced cortical stability by a wide-ranged control on synaptic transmission and plasticity. NEW & NOTEWORTHY We explore the role of astrocyte-mediated gliotransmission in maintenance of olfactory discrimination learning-induced modifications. We show that blocking gap junctions between astrocytes decreases significantly the ability to induce long-term potentiation in the piriform cortex after learning only. In parallel, synaptic inhibition is reduced in neurons from trained rats only, to the level of prelearning. Thus gliotransmission has a key role in maintaining learning-induced cortical stability by a wide-ranged control on synaptic transmission and plasticity.

Facilitatory role of somatostatin via muscarinic cholinergic system in the generation of long-term potentiation in the rat dentate gyrus in vivo

1996 ◽  
Vol 723 (1-2) ◽  
pp. 135-140 ◽  
Author(s):  
Aya Nakata ◽  
Hiroshi Saito ◽  
Nobuyoshi Nishiyama
Keyword(s):  
Dentate Gyrus ◽  
Cholinergic System ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Muscarinic Cholinergic

scholarly journals Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 175
Author(s):  
Jennifer Mayordomo-Cava ◽  
Guillermo Iborra-Lázaro ◽  
Souhail Djebari ◽  
Sara Temprano-Carazo ◽  
Irene Sánchez-Rodríguez ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Amyloid Β ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Biologically Active ◽  
Network Activity ◽  
Oscillatory Activity ◽  
In Vivo Model

In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-β (Aβ) peptides have been shown to play a causal role. Among different Aβ species, Aβ25–35 has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble Aβ forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of Aβ25–35 we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to Schaffer collaterals. Aβ25–35 was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in Aβ25–35 amyloidosis model.

[Gly14]-humanin rescues long-term potentiation from amyloid β protein-induced impairment in the rat hippocampal CA1 region in vivo

Synapse ◽  
2010 ◽  
Vol 64 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Fen Guo ◽  
Wei Jing ◽  
Cun-Gen Ma ◽  
Mei-Na Wu ◽  
Jun-Fang Zhang ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Long Term Potentiation ◽  
Amyloid Β Protein ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Β Protein ◽  
Term Potentiation ◽  
Hippocampal Ca1

scholarly journals Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system.

1995 ◽  
Vol 131 (6) ◽  
pp. 1789-1800 ◽  
Author(s):  
Y Takei ◽  
A Harada ◽  
S Takeda ◽  
K Kobayashi ◽  
S Terada ◽  
...  
Keyword(s):  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Synapsin I ◽  
Term Potentiation ◽  
Gene Mutant ◽  
Associated Proteins ◽  
Hippocampal Ca3

Synapsin I is one of the major synaptic vesicle-associated proteins. Previous experiments implicated its crucial role in synaptogenesis and transmitter release. To better define the role of synapsin I in vivo, we used gene targeting to disrupt the murine synapsin I gene. Mutant mice lacking synapsin I appeared to develop normally and did not have gross anatomical abnormalities. However, when we examined the presynaptic structure of the hippocampal CA3 field in detail, we found that the sizes of mossy fiber giant terminals were significantly smaller, the number of synaptic vesicles became reduced, and the presynaptic structures altered, although the mossy fiber long-term potentiation remained intact. These results suggest significant contribution of synapsin I to the formation and maintenance of the presynaptic structure.

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