Reelin haploinsufficiency reduces the density of PV+ neurons in circumscribed regions of the striatum and selectively alters striatal-based behaviors.
BACKGROUND
Reelin, a large extracellular matrix glycoprotein, is down-regulated in the brain of schizophrenic patients and of heterozygous reeler mice (rl/+). The behavioral phenotype of rl/- mice, however, matches only partially the schizophrenia hallmarks.


OBJECTIVE
We recently reported (Marrone et al., Eur J Neurosci 24:20062-22070, 2006) that homozygous reeler mutants (rl/rl) exhibit reduced density of parvalbumin-positive (PV+) GABAergic interneurons in anatomically circumscribed regions of the neostriatum. Assuming that in rl/+ mice may also show regional reduction of striatal GABAergic interneurons, behavioral impairments should selectively emerge in tasks depending on specifically altered striatal circuits.


METHODS
We mapped the density of striatal PV+ interneurons in rl/+ and wild-type (+/+) mice and measured their performance in tasks depending on distinct striatal subregions.


RESULTS
Our findings show that, contrary to what would be expected on the basis of gene dosage criteria, the striatal regions in which rl/rl mice exhibited decreased density of PV+ interneurons were either unaltered (rostral striatum) or equally altered (dorsomedial and ventromedial intermediate striatum, caudal striatum) in rl/+ mice. The anatomical findings were paralleled by behavioral deficits in fear extinction and latent inhibition, respectively, requiring the dorsomedial and ventromedial striatal regions. Conversely, active avoidance performance, which requires the dorsolateral region, was unaffected.


CONCLUSIONS
Reelin haploinsufficiency alters the density of PV+ neurons in circumscribed regions of the striatum and selectively disrupts behaviors sensitive to dysfunction of these targeted regions. This aspect should be considered when designing experiments aimed at evaluating the impact of reelin haploinsufficiency in schizophrenia-associated cognitive disturbances in rl/+ mutants.
Ammassari-Teule
Martine
M
Department of Experimental Neurology, IRCCS Santa Lucia Foundation, Rome, Italy. martine.teule@ipsifar.rm.cnr.it
Sgobio
Carmelo
C
Biamonte
Filippo
F
Marrone
Cristina
C
Mercuri
Nicola B
NB
Keller
Flavio
F
D000161:Acoustic Stimulation; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002452:Cell Count; D005108:Extinction, Psychological / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005239:Fear / Q000502:physiology; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D007150:Immunohistochemistry; D007395:Interneurons / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D017072:Neostriatum / Q000166:cytology* / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D000091042:Reelin Protein; D005680:gamma-Aminobutyric Acid; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases