Psychopharmacology

, Volume 204, Issue 3, pp 511–521

Reelin haploinsufficiency reduces the density of PV+ neurons in circumscribed regions of the striatum and selectively alters striatal-based behaviors

  • Martine Ammassari-Teule
  • Carmelo Sgobio
  • Filippo Biamonte
  • Cristina Marrone
  • Nicola B. Mercuri
  • Flavio Keller
Original Investigation

DOI: 10.1007/s00213-009-1483-x

Cite this article as:
Ammassari-Teule, M., Sgobio, C., Biamonte, F. et al. Psychopharmacology (2009) 204: 511. doi:10.1007/s00213-009-1483-x

Abstract

Rationale

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.

Objectives

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.

Materials and 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 haploinsufficency in schizophrenia-associated cognitive disturbances in rl/+ mutants.

Keywords

Heterozygous reeler mutationParvalbumin-positive neuronsStriatal regionsStriatal-based cognitive operations

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Martine Ammassari-Teule
    • 1
    • 3
  • Carmelo Sgobio
    • 1
  • Filippo Biamonte
    • 2
  • Cristina Marrone
    • 1
  • Nicola B. Mercuri
    • 1
    • 4
  • Flavio Keller
    • 2
  1. 1.Department of Experimental NeurologyIRCCS Santa Lucia FoundationRomeItaly
  2. 2.Laboratory of Developmental Neuroscience, PRABBUniversity Campus Bio-MedicoRomeItaly
  3. 3.CNR Institute for NeuroscienceRomeItaly
  4. 4.Department of NeuroscienceUniversity of Tor VergataRomeItaly