Assessment of cognitive function in the heterozygous reeler mouse.
BACKGROUND
The heterozygous reeler mouse has been proposed as a genetic mouse model of schizophrenia based on several neuroanatomical and behavioral similarities between these mice and patients with schizophrenia. However, the effect of reelin haploinsufficiency on one of the cardinal symptoms of schizophrenia, the impairment of prefrontal-cortex-dependent cognitive function, has yet to be determined.


OBJECTIVE
Here, we investigated multiple aspects of cognitive function in heterozygous reeler mice that are known to be impaired in schizophrenic patients.


METHODS
Heterozygous reeler mice were assessed for (1) cognitive flexibility in an instrumental reversal learning task, (2) impulsivity in an inhibitory control task, (3) attentional function in a three-choice serial reaction time task, and (4) working memory in a delayed matching-to-position task.


RESULTS
No differences were found between heterozygous reeler mice and wild-type littermate controls in any prefrontal-related cognitive measures. However, heterozygous reeler mice showed deficits in the acquisition of two operant tasks, consistent with a role for reelin in certain forms of learning.


CONCLUSIONS
These findings suggest that heterozygous reeler mice may not be an appropriate model for the core prefrontal-dependent cognitive deficits observed in schizophrenia, but may model more general learning deficits that are associated with many psychiatric disorders.
Krueger
Dilja D
DD
Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, Ribicoff Research Facilities, CMHC, 34 Park Street, New Haven, CT 06508, USA.
Howell
Jessica L
JL
Hebert
Britni F
BF
Olausson
Peter
P
Taylor
Jane R
JR
Nairn
Angus C
AC
D000818:Animals; D001288:Attention; D001522:Behavior, Animal; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D003071:Cognition; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism; D007175:Impulsive Behavior / Q000235:genetics; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000523:psychology*; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D000091042:Reelin Protein; D012193:Reversal Learning; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013037:Spatial Behavior; D013997:Time Factors
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases