Explore the groundbreaking study where scientists reverse PTSD symptoms in mice by targeting a specific brain channel, potentially paving the way for innovative treatments in human brain disorders.
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Restoring the Function of Thalamocortical Circuit Through Correcting Thalamic Kv3.2 Channelopathy Normalizes Fear Extinction Impairments in a PTSD Mouse Model.
Xiao et al., Adv Sci (Weinh) 2023
DOI: 10.1002/advs.202305939
Study Highlights:
- New Findings: Identification of the mediodorsal thalamic nucleus (MD) hyperactivity during fear extinction and its encoding patterns using machine learning algorithms.
- Importance: This study provides insights into the neural substrates of impaired fear memory extinction in PTSD, a symptom with limited therapeutic options.
- Contribution to Literature: The research uncovers the role of the MD-ACC parvalbumin interneurons circuit and its disruption in PTSD, as well as the involvement of decreased phosphorylation of the Kv3.2 channel in the hyperactivity of the MD.
- Therapeutic Insights: A novel RNA therapy strategy targeting the protein phosphatase 6 catalytic subunit is shown to correct channelopathy and restore fear memory extinction in PTSD mice.
Results:
The study found that the MD-ACC circuit, particularly the MD-ACC parvalbumin interneurons, is enhanced in PTSD mice, leading to an imbalance in local excitatory and inhibitory signals. This imbalance is partly due to decreased phosphorylation of the Kv3.2 channel. By employing a lipid nanoparticle-based RNA therapy, targeting the protein phosphatase 6 catalytic subunit, the researchers were able to correct the channelopathy and restore fear memory extinction in PTSD mice.