Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons

Giuseppe Sciamanna, Francesco Napolitano, Barbara Pelosi, Paola Bonsi, Daniela Vitucci, Tommaso Nuzzo, Daniela Punzo, Veronica Ghiglieri, Giulia Ponterio, Massimo Pasqualetti, Antonio Pisani, Alessandro Usiello

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Ras homolog enriched in striatum (Rhes) is highly expressed in striatal medium spiny neurons (MSNs) of rodents. In the present study, we characterized the expression of Rhes mRNA across species, as well as its functional role in other striatal neuron subtypes. Double in situ hybridization analysis showed that Rhes transcript is selectively localized in striatal cholinergic interneurons (ChIs), but not in GABAergic parvalbumin- or in neuropeptide Y-positive cell populations. Rhes is closely linked to dopamine-dependent signaling. Therefore, we recorded ChIs activity in basal condition and following dopamine receptor activation. Surprisingly, instead of an expected dopamine D2 receptor (D2R)-mediated inhibition, we observed an aberrant excitatory response in ChIs from Rhes knockout mice. Conversely, the effect of D1R agonist on ChIs was less robust in Rhes mutants than in controls. Although Rhes deletion in mutants occurs throughout the striatum, we demonstrate that the D2R response is altered specifically in ChIs, since it was recorded in pharmacological isolation, and prevented either by intrapipette BAPTA or by GDP-β-S. Moreover, we show that blockade of Cav2.2 calcium channels prevented the abnormal D2R response. Finally, we found that the abnormal D2R activation in ChIs was rescued by selective PI3K inhibition thus suggesting that Rhes functionally modulates PI3K/Akt signaling pathway in these neurons. Our findings reveal that, besides its expression in MSNs, Rhes is localized also in striatal ChIs and, most importantly, lack of this G-protein, significantly alters D2R modulation of striatal cholinergic excitability.

Original languageEnglish
Pages (from-to)146-161
Number of pages16
JournalNeurobiology of Disease
Volume78
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Corpus Striatum
Dopamine D2 Receptors
Interneurons
Cholinergic Agents
Neurons
Phosphatidylinositol 3-Kinases
Cholinergic Agonists
Parvalbumins
Neuropeptide Y
Dopamine Receptors
Calcium Channels
GTP-Binding Proteins
Knockout Mice
In Situ Hybridization
Rodentia
Dopamine
Pharmacology
Messenger RNA
Population

Keywords

  • Calcium
  • Cholinergic interneurons
  • D2 dopamine receptors
  • Dystonia
  • Rhes
  • Striatum

ASJC Scopus subject areas

  • Neurology

Cite this

Sciamanna, G., Napolitano, F., Pelosi, B., Bonsi, P., Vitucci, D., Nuzzo, T., ... Usiello, A. (2015). Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons. Neurobiology of Disease, 78, 146-161. https://doi.org/10.1016/j.nbd.2015.03.021

Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons. / Sciamanna, Giuseppe; Napolitano, Francesco; Pelosi, Barbara; Bonsi, Paola; Vitucci, Daniela; Nuzzo, Tommaso; Punzo, Daniela; Ghiglieri, Veronica; Ponterio, Giulia; Pasqualetti, Massimo; Pisani, Antonio; Usiello, Alessandro.

In: Neurobiology of Disease, Vol. 78, 01.06.2015, p. 146-161.

Research output: Contribution to journalArticle

Sciamanna, G, Napolitano, F, Pelosi, B, Bonsi, P, Vitucci, D, Nuzzo, T, Punzo, D, Ghiglieri, V, Ponterio, G, Pasqualetti, M, Pisani, A & Usiello, A 2015, 'Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons', Neurobiology of Disease, vol. 78, pp. 146-161. https://doi.org/10.1016/j.nbd.2015.03.021
Sciamanna, Giuseppe ; Napolitano, Francesco ; Pelosi, Barbara ; Bonsi, Paola ; Vitucci, Daniela ; Nuzzo, Tommaso ; Punzo, Daniela ; Ghiglieri, Veronica ; Ponterio, Giulia ; Pasqualetti, Massimo ; Pisani, Antonio ; Usiello, Alessandro. / Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons. In: Neurobiology of Disease. 2015 ; Vol. 78. pp. 146-161.
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AU - Punzo, Daniela

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