The neurotoxin 1-methyl-4-phenylpyridinium (MPP+) alters hippocampal excitatory synaptic transmission by modulation of the GABAergic system

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson’s disease-like symptoms following administration to mice, monkeys, and humans. A common view is that MPTP is metabolized to 1-methyl-4-phenylpyridinium ion (MPP+) to induce its neurodegenerative effects on dopaminergic neurons in the substantia nigra (SN). Moreover, the hippocampus contains dopaminergic fibers, which are projecting from the ventral tegmental area, SN and pars compacta and contain the whole machinery required for dopamine synthesis making them sensitive to MPTP and MPP+. Here, we present data showing that acute bath-application of MPP+ elicited a dose-dependent facilitation followed by a depression of synaptic transmission of hippocampal Schaffer collaterals-CA1 synapses in mice. The effects of MPP+ were not mediated by D1/D5- and D2-like receptor activation. Inhibition of the dopamine transporters did not prevent but increased the depression of excitatory post-synaptic field potentials. In the search for a possible mechanism, we observed that MPP+ reduced the appearance of polyspikes in population spikes recorded in str. pyramidale and increased the frequency of miniature inhibitory post-synaptic currents. The acute effect of MPP+ on synaptic transmission was attenuated by co-application of a GABAA receptor antagonist. Taking these data together, we suggest that MPP+ affects hippocampal synaptic transmission by enhancing some aspects of the hippocampal GABAergic system.

• Publication year

  2015

• Venue

  Frontiers in Cellular Neuroscience

• Publication date

  2015-08-04

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.3389/fncel.2015.00299PMID 26300734PMCID 4523793
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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