Corticostriatal synaptic plasticity alterations in the R6/1 transgenic mouse model of Huntington's disease

Paolo Calabresi, Veronica Ghiglieri, Federica Campanelli, Gioia Marino, Giuseppina Natale, Barbara Picconi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

3 Citazioni (Scopus)

Abstract

Huntington's disease (HD) is a genetic neurodegenerative condition characterized by abnormal dopamine (DA)–glutamate interactions, severe alterations in motor control, and reduced behavioral flexibility. Experimental models of disease show that during symptomatic phases, HD shares with other hyperkinetic disorders the loss of synaptic depotentiation in the striatal spiny projection neurons (SPNs). Here we test the hypothesis that corticostriatal long-term depression (LTD), a well-conserved synaptic scaling down response to environmental stimuli, is also altered in symptomatic male R6/1 mice, a HD model with gradual development of symptoms. In vitro patch-clamp and intracellular recordings of corticostriatal slices from R6/1 mice confirm that, similar to other models characterized by hyperkinesia and striatal DA D1 receptor pathway dysregulation, once long-term potentiation (LTP) is induced, synaptic depotentiation is lost. Our new observations show that activity-dependent LTD was abolished in SPNs of mutant mice. In an experimental condition in which N-methyl-d-aspartate (NMDA) receptors are normally not recruited, in vitro bath application of DA revealed an abnormal response of D1 receptors that caused a shift in synaptic plasticity direction resulting in an NMDA-dependent LTP. Our results demonstrate that corticostriatal LTD is lost in R6/1 mouse model and confirm the role of aberrant DA–glutamate interactions in the alterations of synaptic scaling down associated with HD symptoms.
Lingua originaleEnglish
pagine (da-a)1655-1664
Numero di pagine10
RivistaJournal of Neuroscience Research
Volume97
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • dopamine-dependent plasticity
  • dorsolateral striatum
  • polyglutamine (polyQ) diseases
  • spiny projection neurons

Fingerprint

Entra nei temi di ricerca di 'Corticostriatal synaptic plasticity alterations in the R6/1 transgenic mouse model of Huntington's disease'. Insieme formano una fingerprint unica.

Cita questo