GABA-activated slow spontaneous inhibitory postsynaptic currents are decreased in dorsal hippocampal dentate gyrus granule cells in an aged mouse model of Alzheimer's disease

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

Background Synaptic transmission dysfunction is associated with a range of neurological disorders, including Alzheimer's disease (AD). However, the role γ-aminobutyric acid (GABA)-mediated synaptic inhibition in AD has not been fully explored. Objective We studied basal, GABA-activated slow spontaneous currents (sIPSCs) dentate gyrus (DG) granule cells dorsal hippocampus an mouse model (tg-APPSwe) and investigated insulin's modulatory effects. Methods sIPSCs were recorded DG by whole-cell patch­-clamp recordings hippocampal brain slices from 5–6 (adult) 10–12 (aged) months old wild-type (WT) mice, presence or absence insulin (1 nM). Results The median 10–90% rise time significantly decreased age (10–12 vs. months) only mice. amplitude was adult aged mice as compared to WT whereas frequency reduced 63% decay total current density IPSCs both Insulin application exerted no effect on properties any animal groups. Conclusions characteristics are altered age- disease-state, negligible

Language: Английский

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Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 8, 2024

Alzheimer's disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed human animal studies. GABAergic interneurons (INs) within hippocampus coordinate network activity, which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide calretinin play a crucial role. These provide primarily disinhibition principal excitatory (PCs) CA1 region, regulating incoming inputs formation. However, it remains unclear whether AD pathology induces changes activity of I-S3 cells, impacting motifs. Here, using young adult 3xTg-AD mice, we found that while density morphology remain unaffected, there were significant their firing output. Specifically, displayed elongated action potentials decreased rates, was associated with reduced inhibition INs higher recruitment during spatial decision-making object exploration tasks. Furthermore, activation PCs also impacted, signifying early disruptions functionality. findings suggest altered patterns might initiate early-stage dysfunction circuits, potentially influencing progression pathology.

Language: Английский

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Disinhibition Is an Essential Network Motif Coordinated by GABA Levels and GABA B Receptors

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1340 - 1340

Published: Jan. 22, 2024

Network dynamics are crucial for action and sensation. Changes in synaptic physiology lead to the reorganization of local microcircuits. Consequently, functional state network impacts output signal depending on firing patterns its units. Networks exhibit steady states which neurons show various activities, producing many networks with diverse properties. Transitions between determine generated results. The temporal excitation/inhibition allow a shift an operational network. Therefore, process capable modulating may be functionally important. This is known as disinhibition. In this review, we describe effect GABA levels GABAB receptors tonic inhibition, causes changes (due disinhibition) dynamics, leading synchronous oscillations.

Language: Английский

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Entorhinal cortex–hippocampal circuit connectivity in health and disease

Frontiers in Human Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Sept. 20, 2024

The entorhinal cortex (EC) and hippocampal (HC) connectivity is the main source of episodic memory formation consolidation. entorhinal–hippocampal (EC-HC) connection classified as canonically glutamatergic and, more recently, has been characterized a non-canonical GABAergic connection. Recent evidence shows that both EC HC receive inputs from dopaminergic, cholinergic, noradrenergic projections modulate mnemonic processes linked to encoding consolidation memories. In present review, we address latest findings on EC-HC role neuromodulations during mechanisms memories highlight value cross-species approach unravel underlying cellular known. Furthermore, discuss how early neurodegeneration may contribute dysfunction observed in aging Alzheimer’s disease (AD). Finally, described exercise be fundamental tool prevent or decrease neurodegeneration.

Language: Английский

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Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

Published: April 8, 2024

Alzheimer’s disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed human animal studies. GABAergic interneurons (INs) within hippocampus coordinate network activity, which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide calretinin play a crucial role. These provide primarily disinhibition principal excitatory (PCs) CA1 region, regulating incoming inputs formation. However, it remains unclear whether AD pathology induces changes activity of I-S3 cells, impacting motifs. Here, using young adult 3xTg-AD mice, we found that while density morphology IS-3 remain unaffected, there were significant their firing output. Specifically, displayed elongated action potentials decreased rates, was associated with reduced inhibition INs higher recruitment during spatial decision-making object exploration tasks. Furthermore, activation PCs also impacted, signifying early disruptions functionality. findings suggest altered patterns might initiate early-stage dysfunction circuits, potentially influencing progression pathology.

Language: Английский

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Genetic approaches to elucidating cortical and hippocampal GABAergic interneuron diversity

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 24, 2024

GABAergic interneurons (INs) in the mammalian forebrain represent a diverse population of cells that provide specialized forms local inhibition to regulate neural circuit activity. Over last few decades, development palette genetic tools along with generation single-cell transcriptomic data has begun reveal molecular basis IN diversity, thereby providing deep insights into how different subtypes function forebrain. In this review, we outline emerging picture cortical and hippocampal speciation as defined by transcriptomics developmental origin summarize strategies have been utilized target specific subtypes, technical considerations inherent each approach. Collectively, these methods greatly facilitated our understanding circuitry via cell type compartment-specific thus illuminated path toward potential therapeutic interventions for variety neurocognitive disorders.

Language: Английский

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Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 13, 2024

Abstract Alzheimer’s disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed human animal studies. GABAergic interneurons (INs) within hippocampus coordinate network activity, which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide calretinin play a crucial role. These provide primarily disinhibition principal excitatory (PCs) CA1 region, regulating incoming inputs formation. However, it remains unclear whether AD pathology induces changes activity of I-S3 cells, impacting motifs. Here, using young adult 3xTg-AD mice, we found that while density morphology remain unaffected, there were significant their firing output. Specifically, displayed elongated action potentials decreased rates, was associated with reduced inhibition INs higher recruitment during spatial decision-making object exploration tasks. Furthermore, activation PCs also impacted, signifying early disruptions functionality. findings suggest altered patterns might initiate early-stage dysfunction circuits, potentially influencing progression pathology. Significance This study examines VIP affected by While these maintain structural integrity, they exhibit mice. correlate enhanced impact cells. shed light on circuits as potential mechanism offer insights into prospective therapeutic targets.

Language: Английский

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Mechanisms and optogenetic control of rhythm slowing associated with Alzheimer’s disease: some views from dynamical modeling

Nonlinear Dynamics, Journal Year: 2024, Volume and Issue: 112(13), P. 11637 - 11659

Published: May 9, 2024

Language: Английский

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Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

Published: Aug. 23, 2024

Alzheimer’s disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed human animal studies. GABAergic interneurons (INs) within hippocampus coordinate network activity, which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide calretinin play a crucial role. These provide primarily disinhibition principal excitatory (PCs) CA1 region, regulating incoming inputs formation. However, it remains unclear whether AD pathology induces changes activity of I-S3 cells, impacting motifs. Here, using young adult 3xTg-AD mice, we found that while density morphology remain unaffected, there were significant their firing output. Specifically, displayed elongated action potentials decreased rates, was associated with reduced inhibition INs higher recruitment during spatial decision-making object exploration tasks. Furthermore, activation PCs also impacted, signifying early disruptions functionality. findings suggest altered patterns might initiate early-stage dysfunction circuits, potentially influencing progression pathology.

Language: Английский

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Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Sept. 12, 2024

Alzheimer’s disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed human animal studies. GABAergic interneurons (INs) within hippocampus coordinate network activity, which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide calretinin play a crucial role. These provide primarily disinhibition principal excitatory (PCs) CA1 region, regulating incoming inputs formation. However, it remains unclear whether AD pathology induces changes activity of I-S3 cells, impacting motifs. Here, using young adult 3xTg-AD mice, we found that while density morphology remain unaffected, there were significant their firing output. Specifically, displayed elongated action potentials decreased rates, was associated with reduced inhibition INs higher recruitment during spatial decision-making object exploration tasks. Furthermore, activation PCs also impacted, signifying early disruptions functionality. findings suggest altered patterns might initiate early-stage dysfunction circuits, potentially influencing progression pathology.

Language: Английский

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