GABAergic inhibition in dual-transmission cholinergic and GABAergic striatal interneurons is abolished in Parkinson disease
| Autor: | M. Billon-Grand, Robin Cloarec, Laurie-Anne Gouty-Colomer, N. Oumar, Amandine Dufour, Alexandre Pons-Bennaceur, Constance Hammond, Yehezkel Ben-Ari, Sanaz Eftekhari, Baptiste Riffault, Nail Burnashev, Natalia Lozovaya |
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| Přispěvatelé: | ISARA-Lyon, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), PRA, Fanny |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Patch-Clamp Techniques Vesicular Inhibitory Amino Acid Transport Proteins Dopamine striatum Parkinson's disease Cholinergic Agents Action Potentials General Physics and Astronomy Mice 0302 clinical medicine Sodium Potassium Chloride Symporter Inhibitors Solute Carrier Family 12 Member 2 lcsh:Science Bumetanide gamma-Aminobutyric Acid Neuronal Plasticity Multidisciplinary Glutamate Decarboxylase Chemistry GABA polarity Cholinergic Neurons 3. Good health Parkinson disease ACh/GABA cotransmission Excitatory postsynaptic potential GABAergic [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] medicine.drug Science LIM-Homeodomain Proteins Mice Transgenic Nerve Tissue Proteins Inhibitory postsynaptic potential General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Chlorides Interneurons medicine Animals Humans [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Patch clamp Parkinson Disease Secondary Ion Transport Antagonist General Chemistry Microreview Acetylcholine Corpus Striatum Cellular neuroscience nervous system diseases 030104 developmental biology Gene Expression Regulation Inhibitory Postsynaptic Potentials nervous system Cholinergic lcsh:Q Neuroscience 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) Nature Communications Nature Communications, Nature Publishing Group, 2018, 9 (1), ⟨10.1038/s41467-018-03802-y⟩ Cell Stress |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-03802-y⟩ |
| Popis: | The rule of one terminal and one transmitter acting on one synapse clearly fails to cover the complexity of chemical synapse operation in the brain. Compelling evidence now indicates that two transmitters can be released from the same terminal, acting in a complementary manner to generate complex electrical activity in the targets. Our laboratory now showed that a subpopulation striatal cholinergic neurons also release the classical inhibitory transmitter GABA with a balance between excitation and inhibition being provided by acetylcholine and GABA, respectively. An illustration of the importance of this dual release comes from the fact that when dopamine signals are absent such as in Parkinson disease (PD) the GABAergic inhibition in these dual cholinergic/GABAergic cells fails because of high intracellular chloride ((Cl-)I) levels rendering the cholinergic excitatory component unmet by a parallel inhibitory drive. Restoring low (Cl-)I with the NKCC1 chloride importer antagonist bumetanide attenuates the electrical and motor disturbance. In addition to illustrating the complex interactions between two transmitters acting at the same synapse, this study paves the way to novel conceptual treatment of PD based on restoration of GABAergic inhibition in keeping with our pilot clinical trial showing indeed that bumetanide together with levodopa attenuates axial motor disturbance. It is also in keeping with extensive investigations showing increased (Cl-)I levels and weakened inhibition in a wide range of pathological insults and their restoration by bumetanide. It raises fundamental issues related to the operation of the striatum and basal ganglia in health and disease. |
| Databáze: | OpenAIRE |
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