Altered cortico-striatal synaptic plasticity and related behavioural impairments in reeler mice.
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 gamma-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.
Marrone
Maria Cristina
MC
Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
Marinelli
Silvia
S
Biamonte
Filippo
F
Keller
Flavio
F
Sgobio
Carmelo Alessio
CA
Ammassari-Teule
Martine
M
Bernardi
Giorgio
G
Mercuri
Nicola B
NB
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology*; D003342:Corpus Striatum / Q000166:cytology*; D004298:Dopamine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018755:GABA Agonists / Q000494:pharmacology; D007150:Immunohistochemistry / Q000592:standards; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D009557:Nipecotic Acids / Q000494:pharmacology; D010320:Parvalbumins / Q000378:metabolism; D011336:Probability; D000091042:Reelin Protein; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D009557:Nipecotic Acids; D010320:Parvalbumins; D000091042:Reelin Protein; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; C000717128:Reln protein, mouse; D004298:Dopamine; D000078308:Tiagabine