Subtle alterations of excitatory transmission are linked to presynaptic changes in the hippocampus of PINK1-deficient mice

Marco Feligioni, Dalila Mango, Sonia Piccinin, Paola Imbriani, Filomena Iannuzzi, Alessandra Caruso, Francesca De Angelis, Fabio Blandini, Nicola B. Mercuri, Antonio Pisani, Robert Nisticò

Research output: Contribution to journalArticlepeer-review

Abstract

Homozygous or heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene have been linked to early-onset Parkinson's disease (PD). Several neurophysiological studies have demonstrated alterations in striatal synaptic plasticity along with impaired dopamine release in PINK1-deficient mice. Using electrophysiological methods, here we show that PINK1 loss of function causes a progressive increase of spontaneous glutamate-mediated synaptic events in the hippocampus, without influencing long-term potentiation. Moreover, fluorescence analysis reveals increased neurotrasmitter release although our biochemical results failed to detect which presynaptic proteins might be engaged. This study provides a novel role for PINK1 beyond the physiology of nigrostriatal dopaminergic circuit. Specifically, PINK1 might contribute to preserve synaptic function and glutamatergic homeostasis in the hippocampus, a brain region underlying cognition. The subtle changes in excitatory transmission here observed might be a pathogenic precursor to excitotoxic neurodegeneration and cognitive decline often observed in PD. Using electrophysiological and fluorescence techniques, we demonstrate that lack of PINK1 causes increased excitatory transmission and neurotransmitter release in the hippocampus, which might lead to the cognitive decline often observed in Parkinson's disease.

Original languageEnglish
JournalSynapse
DOIs
Publication statusAccepted/In press - 2016

Keywords

  • Electrophysiology
  • Hippocampus
  • Long-term potentiation
  • Neurotransmitter release
  • Parkinson's disease
  • Synaptic transmission

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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