Altered cortico-striatal synaptic plasticity and related behavioural impairments in reeler mice

Maria Cristina Marrone, Silvia Marinelli, Filippo Biamonte, Flavio Keller, Carmelo Alessio Sgobio, Martine Ammassari-Teule, Giorgio Bernardi, Nicola B. Mercuri

Research output: Contribution to journalArticle

Abstract

Reelin-deficient mice have been used to investigate the role of this extracellular protein in cortico-striatal plasticity and striatum-related behaviours. Here we show that a repetitive electrical stimulation of the cortico-striatal pathway elicited long-term potentiation (LTP) in homozygous reeler (rl/rl) mice, while causing long-term depression in their wild-type (+/+) littermates. The N-methyl-d-aspartic acid (NMDA) receptor antagonist d-(-)-2 amino-5-phosphonopentanoic acid prevented the induction of LTP in (rl/rl) mice, thus confirming that this form of synaptic plasticity was NMDA receptor-dependent. Interestingly, in the presence of tiagabine, a blocker of γ-aminobutyric acid (GABA) re-uptake system, the probability that (rl/rl) mice showed LTP decreased significantly, thus suggesting an impaired GABAergic transmission in reeler mutants. Consistent with this view, a decreased density of parvalbumin-positive GABAergic striatal interneurons was found in (rl/rl) mice in comparison to (+/+) mice. Finally, compatible with their abnormal striatal function (rl/rl) mice exhibited procedural learning deficits. Our data, showing alterations in cortico-striatal plasticity largely depending on a depressed GABAergic tone, delineate a mechanism whereby the lack of reelin may affect cognitive functions.

Original languageEnglish
Pages (from-to)2061-2070
Number of pages10
JournalEuropean Journal of Neuroscience
Volume24
Issue number7
DOIs
Publication statusPublished - Oct 2006

Keywords

  • GABA
  • Long-term depression
  • Long-term potentiation
  • Parvalbumin
  • Procedural learning
  • Reelin

ASJC Scopus subject areas

  • Neuroscience(all)

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    Marrone, M. C., Marinelli, S., Biamonte, F., Keller, F., Sgobio, C. A., Ammassari-Teule, M., Bernardi, G., & Mercuri, N. B. (2006). Altered cortico-striatal synaptic plasticity and related behavioural impairments in reeler mice. European Journal of Neuroscience, 24(7), 2061-2070. https://doi.org/10.1111/j.1460-9568.2006.05083.x