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<p>Identifying novel and accessible therapeutic targets for Parkinson’s Disease (PD) remains a pressing goal. Growing evidence implicates cortical dysfunctions in PD-related symptoms, yet the mechanisms—especially those involving parvalbumin-positive interneurons (PV-INs), key regulators of brain oscillations and plasticity—are not fully understood. In this study, we investigate how PD alters PV-IN network and cortical oscillatory dynamics using the 6-hydroxydopamine (6-OHDA) mouse model. Through an integrated approach combining electrophysiological recordings, wide-field calcium imaging, and histological analysis, we reveal a profound cascade of cortical changes. These include pathological hyperactivity above 100 Hz during movement and severe disruptions in PV-IN connectivity across the motor cortex. Synaptic imbalances and microglial activation further point to a multifaceted cortical response to dopaminergic degeneration, revealing inhibitory dysfunction, oscillatory instability, structural remodeling, and neuroinflammation. Our results link PD to cortical instability and highlight cortical plasticity as a promising target for therapeutic intervention.</p><p></p>

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Parkinsonism disrupts cortical function by dysregulating oscillatory, network and synaptic activity of parvalbumin positive interneurons

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Antea Minetti,
  • Elena Montagni,
  • Nicolò Meneghetti,
  • Francesca Macchi,
  • Éléa Coulomb,
  • Alessandra Martello,
  • Alexia Tiberi,
  • Simona Capsoni,
  • Alberto Mazzoni,
  • Anna Letizia Allegra Mascaro,
  • Cristina Spalletti

摘要

Identifying novel and accessible therapeutic targets for Parkinson’s Disease (PD) remains a pressing goal. Growing evidence implicates cortical dysfunctions in PD-related symptoms, yet the mechanisms—especially those involving parvalbumin-positive interneurons (PV-INs), key regulators of brain oscillations and plasticity—are not fully understood. In this study, we investigate how PD alters PV-IN network and cortical oscillatory dynamics using the 6-hydroxydopamine (6-OHDA) mouse model. Through an integrated approach combining electrophysiological recordings, wide-field calcium imaging, and histological analysis, we reveal a profound cascade of cortical changes. These include pathological hyperactivity above 100 Hz during movement and severe disruptions in PV-IN connectivity across the motor cortex. Synaptic imbalances and microglial activation further point to a multifaceted cortical response to dopaminergic degeneration, revealing inhibitory dysfunction, oscillatory instability, structural remodeling, and neuroinflammation. Our results link PD to cortical instability and highlight cortical plasticity as a promising target for therapeutic intervention.