Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function
The motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects...
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2020-04-01
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author | Giuseppe Di Giovanni Laura Clara Grandi Ernesto Fedele Gergely Orban Agnese Salvadè Wei Song Eleonora Cuboni Alessandro Stefani Alain Kaelin-Lang Salvatore Galati |
author_facet | Giuseppe Di Giovanni Laura Clara Grandi Ernesto Fedele Gergely Orban Agnese Salvadè Wei Song Eleonora Cuboni Alessandro Stefani Alain Kaelin-Lang Salvatore Galati |
author_sort | Giuseppe Di Giovanni |
collection | DOAJ |
description | The motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects of acute and chronic dopamine (DA) depletion on the neuronal firing of MTh neurons, cortical/MTh interplay and MTh extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in two states of DA depletion: acute depletion induced by the tetrodotoxin (TTX) and chronic denervation obtained by 6-hydroxydopamine (6-OHDA), both infused into the medial forebrain bundle (MFB) in anesthetized rats. The acute TTX DA depletion caused a clear-cut reduction in MTh neuronal activity without changes in burst content, whereas the chronic 6-OHDA depletion did not modify the firing rate but increased the burst firing. The phase correlation analysis underscored that the 6-OHDA chronic DA depletion affected the MTh-cortical activity coupling compared to the acute TTX-induced DA depletion state. The TTX acute DA depletion caused a clear-cut increase of the MTh GABA concentration and no change of GLU levels. On the other hand, the 6-OHDA-induced chronic DA depletion led to a significant reduction of local GABA and an increase of GLU levels in the MTh. These data show that MTh is affected by DA depletion and support the hypothesis that a rebalancing of MTh in the chronic condition counterbalances the profound alteration arising after acute DA depletion state. |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-2fc19ac0c525471a9346a7cd182e1e5f2023-11-19T21:38:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218273410.3390/ijms21082734Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic FunctionGiuseppe Di Giovanni0Laura Clara Grandi1Ernesto Fedele2Gergely Orban3Agnese Salvadè4Wei Song5Eleonora Cuboni6Alessandro Stefani7Alain Kaelin-Lang8Salvatore Galati9Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida MSD 2080, MaltaLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, 6900 Taverne, SwitzerlandSection of Pharmacology and Toxicology, Department of Pharmacy, Center of Excellence for Biomedical Research, University of Genoa, 16148 Genoa, ItalyLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, 6900 Taverne, SwitzerlandLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, 6900 Taverne, SwitzerlandLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, 6900 Taverne, SwitzerlandLaboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida MSD 2080, MaltaDepartment of system medicine, Faculty of Medicine and Surgery, University of Rome “Tor Vergata”, 00133 Rome, ItalyLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, 6900 Taverne, SwitzerlandLaboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, 6900 Taverne, SwitzerlandThe motor thalamus (MTh) plays a crucial role in the basal ganglia (BG)-cortical loop in motor information codification. Despite this, there is limited evidence of MTh functionality in normal and Parkinsonian conditions. To shed light on the functional properties of the MTh, we examined the effects of acute and chronic dopamine (DA) depletion on the neuronal firing of MTh neurons, cortical/MTh interplay and MTh extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in two states of DA depletion: acute depletion induced by the tetrodotoxin (TTX) and chronic denervation obtained by 6-hydroxydopamine (6-OHDA), both infused into the medial forebrain bundle (MFB) in anesthetized rats. The acute TTX DA depletion caused a clear-cut reduction in MTh neuronal activity without changes in burst content, whereas the chronic 6-OHDA depletion did not modify the firing rate but increased the burst firing. The phase correlation analysis underscored that the 6-OHDA chronic DA depletion affected the MTh-cortical activity coupling compared to the acute TTX-induced DA depletion state. The TTX acute DA depletion caused a clear-cut increase of the MTh GABA concentration and no change of GLU levels. On the other hand, the 6-OHDA-induced chronic DA depletion led to a significant reduction of local GABA and an increase of GLU levels in the MTh. These data show that MTh is affected by DA depletion and support the hypothesis that a rebalancing of MTh in the chronic condition counterbalances the profound alteration arising after acute DA depletion state.https://www.mdpi.com/1422-0067/21/8/2734electrophysiologymicrodialysisimmunohistochemistryL-DOPAdeep brain stimulation |
spellingShingle | Giuseppe Di Giovanni Laura Clara Grandi Ernesto Fedele Gergely Orban Agnese Salvadè Wei Song Eleonora Cuboni Alessandro Stefani Alain Kaelin-Lang Salvatore Galati Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function International Journal of Molecular Sciences electrophysiology microdialysis immunohistochemistry L-DOPA deep brain stimulation |
title | Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function |
title_full | Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function |
title_fullStr | Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function |
title_full_unstemmed | Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function |
title_short | Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function |
title_sort | acute and chronic dopaminergic depletion differently affect motor thalamic function |
topic | electrophysiology microdialysis immunohistochemistry L-DOPA deep brain stimulation |
url | https://www.mdpi.com/1422-0067/21/8/2734 |
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