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

Authors

  • Maria Cristina Marrone,

    1. Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
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  • Silvia Marinelli,

    1. Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
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    • *

      Present address: European Brain Research Institute, Rome, Italy.

  • Filippo Biamonte,

    1. Laboratory of Developmental Neuroscience, University Campus Bio-Medico, Via Longoni 83, 00155 Rome, Italy
    2. Institute of Anatomy and Cell Biology, Catholic University, L.go F. Vito 1, 00168 Rome, Italy
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  • Flavio Keller,

    1. Laboratory of Developmental Neuroscience, University Campus Bio-Medico, Via Longoni 83, 00155 Rome, Italy
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  • Carmelo Alessio Sgobio,

    1. Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
    2. CNR Institute for Neuroscience, IRCCS Santa Lucia Foundation, Rome, Italy
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  • Martine Ammassari-Teule,

    1. Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
    2. CNR Institute for Neuroscience, IRCCS Santa Lucia Foundation, Rome, Italy
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  • Giorgio Bernardi,

    1. Department of Neuroscience, University of Tor Vergata, Rome, Italy
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  • Nicola B. Mercuri

    1. Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
    2. Department of Neuroscience, University of Tor Vergata, Rome, Italy
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Dr N. B. Mercuri, 1Department of Experimental Neurology, as above.
E-mail: mercurin@med.uniroma2.it

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.

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