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Optogenetic Activation of Striatopallidal Neurons Reveals Altered HCN Gating in DYT1 Dystonia.
Sciamanna, Giuseppe; Ponterio, Giulia; Vanni, Valentina; Laricchiuta, Daniela; Martella, Giuseppina; Bonsi, Paola; Meringolo, Maria; Tassone, Annalisa; Mercuri, Nicola Biagio; Pisani, Antonio.
Afiliación
  • Sciamanna G; Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy; Lab of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • Ponterio G; Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy.
  • Vanni V; Lab of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • Laricchiuta D; Department of Psychology, Faculty of Medicine and Psychology, University of Rome Sapienza, Rome, Italy; Lab of Behavioural and Experimental Neurophysiology, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • Martella G; Lab of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • Bonsi P; Lab of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • Meringolo M; Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy.
  • Tassone A; Lab of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • Mercuri NB; Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy; Lab of Experimental Neurology, IRCCS Fondazione Santa Lucia, Rome, Italy.
  • Pisani A; Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy; Lab of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy. Electronic address: pisani@uniroma2.it.
Cell Rep ; 31(7): 107644, 2020 05 19.
Article en En | MEDLINE | ID: mdl-32433955
Firing activity of external globus pallidus (GPe) is crucial for motor control and is severely perturbed in dystonia, a movement disorder characterized by involuntary, repetitive muscle contractions. Here, we show that GPe projection neurons exhibit a reduction of firing frequency and an irregular pattern in a DYT1 dystonia model. Optogenetic activation of the striatopallidal pathway fails to reset pacemaking activity of GPe neurons in mutant mice. Abnormal firing is paralleled by alterations in motor learning. We find that loss of dopamine D2 receptor-dependent inhibition causes increased GABA input at striatopallidal synapses, with subsequent downregulation of hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels. Accordingly, enhancing in vivo HCN channel activity or blocking GABA release restores both the ability of striatopallidal inputs to pause ongoing GPe activity and motor coordination deficits. Our findings demonstrate an impaired striatopallidal connectivity, supporting the central role of GPe in motor control and, more importantly, identifying potential pharmacological targets for dystonia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Chaperonas Moleculares / Optogenética / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización / Neuronas Límite: Animals Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Chaperonas Moleculares / Optogenética / Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización / Neuronas Límite: Animals Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos