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TREK-1 Null Impairs Neuronal Excitability, Synaptic Plasticity, and Cognitive Function.
Wei Wang1,2, Conrad M Kiyoshi1, Yixing Du1
1Department of Neuroscience, Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Molecular Neurobiology
|November 16, 2019
Summary
TREK-1 deficiency in mice enhances neuronal structure and excitability, impairing recognition memory. This suggests TREK-1 channels regulate cognitive function by controlling neuronal morphology and synaptic plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
- Channelopathy
Background:
- TREK-1 (a two-pore-domain K+ channel) is highly expressed in the central nervous system.
- Aberrant TREK-1 expression is linked to cognitive impairment, but its mechanisms are unclear.
Purpose of the Study:
- To investigate the role of TREK-1 in neuronal morphology, excitability, synaptic plasticity, and cognitive function using TREK-1 knockout mice.
Main Methods:
- TREK-1 immunostaining in mouse hippocampus.
- Analysis of dendritic morphology and spine density in TREK-1 knockout (KO) mice.
- Electrophysiological recordings to assess neuronal excitability and synaptic currents (EPSCs, IPSCs).
- Evaluation of long-term potentiation (LTP) and paired-pulse ratio.
- Assessment of cognitive function, specifically recognition memory.
Main Results:
- TREK-1 KO increased dendritic sprouting and immature spines in hippocampal CA1 pyramidal neurons.
- TREK-1 KO enhanced neuronal excitability and both excitatory and inhibitory postsynaptic currents.
- Increased presynaptic glutamate release probability and postsynaptic AMPA receptor expression contributed to enhanced EPSCs.
- TREK-1 KO decreased paired-pulse ratio and occluded LTP, indicating altered synaptic plasticity.
- TREK-1 KO mice exhibited deficits in recognition memory.
- TREK-1 KO did not affect astrocyte function.
Conclusions:
- TREK-1 deficiency profoundly impacts hippocampal pyramidal neuron structure and function.
- Impaired cognitive function in diseases with aberrant TREK-1 expression may stem from this channel's failure to regulate neuronal morphology, excitability, synaptic transmission, and plasticity.
Keywords:
Cognitive impairmentHippocampusSynaptic plasticitySynaptic transmissionTREK-1 (tandem of pore domain in a weak inwardly rectifying K+ channel (Twik)-related K+ channels)More Related Videos
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