title: Behavioral Resilience and Sensitivity to Locally Restricted Cortical Migration Deficits Induced by In Utero Knockdown of Disabled-1 in the Adult Rat.
abstract: Irregular neuronal migration plays a causal role in mental illnesses such as schizophrenia and autism, but the very nature of the migration deficits necessary to evoke adult behavioral changes is unknown. Here, we used in utero electroporation (IUE) in rats to induce a locally restricted, cortical migration deficit by knockdown of disabled-1 (Dab1), an intracellular converging point of the reelin pathway. After birth, selection of successfully electroporated rats by detection of in vivo bioluminescence of a simultaneously electroporated luciferase gene correlated to and was thus predictive to the number of electroporated neurons in postmortem histochemistry at 6 months of age. Rat neurons silenced for Dab1 did not migrate properly and their number surprisingly decreased after E22. Behavioral tests at adult ages (P180) revealed increased sensitivity to amphetamine as well as decreased habituation, but no deficits in memory tasks or motor functions. The data suggest that even subtle migration deficits involving only ten-thousands of cortical neurons during neurodevelopment can lead to lasting behavioral and neuronal changes into adulthood in some very specific behavioral domains. On the other hand, the lack of effects on various memory-related tasks may indicate resilience and plasticity of cognitive functions critical for survival under these specific conditions.
authors.affiliation: Department Neuropathology.
authors.forename: Sandra
authors.initials: S
authors.lastname: Vomund
authors.affiliation: Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich-Heine University Düsseldorf, Düsseldorf 40225, Germany.
authors.forename: M Angelica
authors.initials: MA
authors.lastname: de Souza Silva
authors.affiliation: Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich-Heine University Düsseldorf, Düsseldorf 40225, Germany.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Huston
authors.affiliation: Department Neuropathology.
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000254:growth & development* / Q000503:physiopathology*; D004195:Disease Models, Animal; D018274:Electroporation; D055785:Gene Knockdown Techniques; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000503:physiopathology; D065886:Neurodevelopmental Disorders / Q000209:etiology / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D055500:Resilience, Psychological
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000697:Central Nervous System Stimulants; C499786:Dab1 protein, rat; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D000661:Amphetamine; C000717127:RELN protein, human
keywords: Dab1; bioluminescence live imaging; cortical migration deficits; in utero electroporation; neurodevelopment