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

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...

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Published in:International journal of molecular sciences 2019-03, Vol.20 (5), p.1168
Main Authors: Sánchez-Rodríguez, Irene, Gruart, Agnès, Delgado-García, José María, Jiménez-Díaz, Lydia, Navarro-López, Juan D
Format: Article
Language:English
Subjects:
Adenosine
Amyloid
Channels
Dopamine
G protein-coupled receptors
Hippocampus
Long-term potentiation
Narcotics
Neuromodulation
Neurotransmitters
Opioid receptors
Pathology
Potassium channels (inwardly-rectifying)
Proteins
Serotonin
Somatostatin
Synaptic plasticity
Synaptic transmission
Tertiapin-Q
γ-Aminobutyric acid A receptors
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Summary: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- (A ) or GirK channel modulators impaired ionotropic (GABA -mediated fPSPs) and metabotropic (GirK-mediated fPSPs) inhibitory signaling and disrupted the potentiation of synaptic inhibition. However, the activation of GirK channels prevented A -induced changes in GABA components. Our data shows, for the first time, the presence of long-term potentiation (LTP) for both the GABA 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20051168