L-DOPA reverses the impairment of Dentate Gyrus LTD in experimental parkinsonism via β-adrenergic receptors

Valentina Pendolino, Vincenza Bagetta, Veronica Ghiglieri, Carmelo Sgobio, Emanuela Morelli, Silvia Poggini, Igor Branchi, Emanuele C. Latagliata, Tiziana Pascucci, Stefano Puglisi-Allegra, Paolo Calabresi, Barbara Picconi

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson's disease (PD) patients exhibit motor and non-motor symptoms that severely affect quality of life. Cognitive alterations in PD subjects have been related to both structural and functional hippocampal changes. Here we investigated the effects of the 6-hydroxydopamine (6-OHDA) lesion in the Medial Forebrain Bundle (MFB) on the hippocampus focusing on the Dentate Gyrus (DG). In vivo microdialysis measurements revealed that the 6-OHDA injection disrupts both dopaminergic and noradrenergic transmission in rat DG. In vitro electrophysiological recordings showed that these neurochemical alterations were accompanied by impairment of long-term depression (LTD) at medial perforant path/DG synapses. Furthermore, this alteration was reversed by l-DOPA treatment. Notably, the therapeutic effect of l-DOPA on LTD was blocked by the antagonism of β-noradrenergic receptors, but not by dopamine D1 or D2 receptor antagonists. Thus, while the dopaminergic transmission does not seem to be implicated in this therapeutic effect of l-DOPA, the noradrenergic system plays a central role in the synaptic dysfunction of the DG in experimental PD. Our work provides new evidence on the role of catecholamines in DG synaptic plasticity and sheds light on the possible synaptic mechanisms underlying cognitive deficits in PD. Furthermore, our results indicate that l-DOPA exerts a therapeutic effect on the parkinsonian brain through different, coexistent, mechanisms.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalExperimental Neurology
Volume261
DOIs
Publication statusPublished - 2014

Keywords

  • Dentate Gyrus
  • Long-term depression
  • Parkinson's disease
  • Synaptic plasticity
  • Whole-cell patch clamp recordings

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Medicine(all)

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