Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function

Giuseppe Di Giovanni, Laura Clara Grandi, Ernesto Fedele, Gergely Orban, Agnese Salvadè, Wei Song, Eleonora Cuboni, Alessandro Stefani, Alain Kaelin-Lang, Salvatore Galati

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number8
DOIs
Publication statusPublished - Apr 15 2020

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Keywords

  • deep brain stimulation
  • electrophysiology
  • immunohistochemistry
  • L-DOPA
  • microdialysis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Di Giovanni, G., Grandi, L. C., Fedele, E., Orban, G., Salvadè, A., Song, W., Cuboni, E., Stefani, A., Kaelin-Lang, A., & Galati, S. (2020). Acute and Chronic Dopaminergic Depletion Differently Affect Motor Thalamic Function. International Journal of Molecular Sciences, 21(8). https://doi.org/10.3390/ijms21082734