Prolonged epigenetic and synaptic plasticity alterations following single exposure to a psychedelic in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA678963 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13073900.fastq.gz | Fastqsanger.gz | |||
| SRR13073901.fastq.gz | Fastqsanger.gz | |||
| SRR13073902.fastq.gz | Fastqsanger.gz | |||
| SRR13073903.fastq.gz | Fastqsanger.gz | |||
| SRR13073904.fastq.gz | Fastqsanger.gz |
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Project description:Li2012 Calcium mediated synaptic
plasticity
This model is an extension of
BIOMD0000000183.
This model is described in the article:
Calcium input frequency,
duration and amplitude differentially modulate the relative
activation of calcineurin and CaMKII.
Li L, Stefan MI, Le Novère
N.
PLoS ONE 2012; 7(9): e43810
Abstract:
NMDA receptor dependent long-term potentiation (LTP) and
long-term depression (LTD) are two prominent forms of synaptic
plasticity, both of which are triggered by post-synaptic
calcium elevation. To understand how calcium selectively
stimulates two opposing processes, we developed a detailed
computational model and performed simulations with different
calcium input frequencies, amplitudes, and durations. We show
that with a total amount of calcium ions kept constant, high
frequencies of calcium pulses stimulate calmodulin more
efficiently. Calcium input activates both calcineurin and
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) at all
frequencies, but increased frequencies shift the relative
activation from calcineurin to CaMKII. Irrespective of
amplitude and duration of the inputs, the total amount of
calcium ions injected adjusts the sensitivity of the system to
calcium input frequencies. At a given frequency, the quantity
of CaMKII activated is proportional to the total amount of
calcium. Thus, an input of a small amount of calcium at high
frequencies can induce the same activation of CaMKII as a
larger amount, at lower frequencies. Finally, the extent of
activation of CaMKII signals with high calcium frequency is
further controlled by other factors, including the availability
of calmodulin, and by the potency of phosphatase
inhibitors.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000628.
To cite BioModels Database, please use:
BioModels Database:
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To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000628 | BioModels
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2025-08-01 | GSE288931 | GEO
Project description:Homeostatic synaptic plasticity (HSP) is a fundamental neuronal mechanism that allows networks to compensate for prolonged changes in activity by adjusting synaptic strength. This process is crucial for maintaining stable brain function and has been implicated in memory consolidation during sleep. While scaling of both excitatory and inhibitory synapses plays an important role during homeostatic synaptic plasticity, molecules coordinating both of these processes are unknown. In this study, we investigate the role of miR-218-5p as a regulator of inhibitory and excitatory synapses in the context of picrotoxin (PTX)-induced homeostatic synaptic downscaling (HSD) in rat hippocampal neurons. Using enrichment analysis of miRNA-binding sites in differentially expressed genes changing upon PTX-induced HSD, we bioinformatically predicted and experimentally validated increased miR-218-5p activity upon PTX-treatment in the process compartment. By monitoring synapse structure in vitro with confocal microscopy, we demonstrate that miR-218-5p exerts a dual effect in HSD: it prevents the downscaling of excitatory synapses and dendritic spines, while at the same time blocking inhibitory synapse upscaling. Furthermore, we identify the Neuroligin2 interacting molecule Mdga1 as a crucial target of miR-218-5p in the context of homeostatic upscaling of inhibitory synapses. By performing long-term electroencephalographic (EEG) recordings, we further revealed that local inhibition of miR-218-5p in the somatosensory cortex reduced local slow-wave activity (SWA) during non-rapid-eye-movement (NREM) sleep. In summary, this study uncovers miR-218-5p as a key player in coordinating inhibitory and excitatory synapses during homeostatic plasticity and sleep. Our findings contribute to a deeper understanding of how neural circuits maintain stability in the face of activity-induced perturbations, with potential implications for both physiological and pathological conditions.
2025-03-17 | GSE245158 | GEO