Reelin supplementation recovers sensorimotor gating, synaptic plasticity and associative learning deficits in the heterozygous reeler mouse

• Published in: Journal of psychopharmacology (Oxford) Vol. 27; no. 4; pp. 386 - 395
• Main Authors: Rogers, Justin T, Zhao, Lisa, Trotter, Justin H, Rusiana, Ian, Peters, Melinda M, Li, Qingyou, Donaldson, Erika, Banko, Jessica L, Keenoy, Kathleen E, Rebeck, G William, Hoe, Hyang-Sook, D’Arcangelo, Gabriella, Weeber, Edwin J
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-04-2013; Sage Publications; Sage Publications Ltd
• Subjects: Adult and adolescent clinical studies; Anatomy; Animals; Associative learning; Biological and medical sciences; Cell Adhesion Molecules, Neuronal - genetics; Cell Adhesion Molecules, Neuronal - metabolism; Child clinical studies; Crosses, Genetic; Dendritic spines; Dendritic Spines - metabolism; Dendritic Spines - pathology; Developmental disorders; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Female; Gait Disorders, Neurologic - etiology; Gait Disorders, Neurologic - metabolism; Genotype & phenotype; Glutamate Decarboxylase - metabolism; Heterozygote; Hippocampus; Hippocampus - metabolism; Learning; Learning disorders; Learning Disorders - etiology; Learning Disorders - metabolism; Ligands; lipoprotein receptors; Lipoproteins; Male; Medical sciences; Memory; Mental disorders; Mice; Mice, Neurologic Mutants; Morphogenesis; Morphology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural Inhibition; Neurochemistry; Neuronal Plasticity; Neurons - metabolism; Neuropharmacology; Neuropsychology; Pharmacology. Drug treatments; Plasticity (synaptic); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Reelin protein; Rodents; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - pathology; Schizophrenia - physiopathology; Sensorimotor gating; Sensory Gating; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; Supplementation; Synaptic density; Synaptic Transmission; low-density lipoprotein receptors; hippocampus; learning and memory; Schizophrenia; sensorimotor gating; glutamic acid decarboxylase 67; associative memory; long-term potentiation; Central nervous system; Long term potentiation; Lyases; Encephalon; Psychosis; Learning; Associative memory; Acquisition process; Learning disability; Carboxy-lyases; Synaptic plasticity; Supplementation; Gating; Enzyme; Rodentia; Associative relation; Glutamate decarboxylase; LDL receptor; Carbon-carbon lyases; Vertebrata; Mammalia; Reelin; Mouse; Animal; Hippocampus; and associative memory
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881112463468

The lipoprotein receptor ligand Reelin is important for the processes of normal synaptic plasticity, dendritic morphogenesis, and learning and memory. Heterozygous reeler mice (HRM) show many neuroanatomical, biochemical, and behavioral features that are associated with schizophrenia. HRM show subtle morphological defects including reductions in dendritic spine density, altered synaptic plasticity and behavioral deficits in associative learning and memory and pre-pulse inhibition. The present studies test the hypothesis that in vivo elevation of Reelin levels can rescue synaptic and behavioral phenotypes associated with HRM. We demonstrate that a single in vivo injection of Reelin increases GAD67 expression and alters dendritic spine morphology. In parallel we observed enhancement of hippocampal synaptic function and associative learning and memory. Reelin supplementation also increases pre-pulse inhibition. These results suggest that characteristics of HRM, similar to those observed in schizophrenia, are sensitive to Reelin levels and can be modified with Reelin supplementation in male and female adults.