[en] Despite inherent difficulties to translate human cognitive phenotype into animals, a large number of animal models for psychiatric disorders, such as schizophrenia, have been developed over the last decades. To which extent they reproduce common patterns of dysfunction related to mental illness and abnormal processes of maturation is still largely unknown. While the devastating symptoms of disease are firstly detectable in adulthood, they are considered to reflect profound miswiring of brain circuitry as result of abnormal development. To reveal whether different disease models share common dysfunction early in life, we investigate the prefrontal-hippocampal communication at neonatal age in (a) mice mimicking the abnormal genetic background (22q11.2 microdeletion, DISC1 knockdown), (b) mice mimicking the challenge by environmental stressors (maternal immune activation during pregnancy), (c) mice mimicking the combination of both aetiologies (dual-hit models) and pharmacological mouse models. Simultaneous extracellular recordings in vivo from all layers of prelimbic subdivision (PL) of prefrontal cortex (PFC) and CA1 area of intermediate/ventral hippocampus (i/vHP) show that network oscillations have a more fragmented structure and decreased power mainly in neonatal mice that mimic both genetic and environmental aetiology of disease. These mice also show layer-specific firing deficits in PL. Similar early network dysfunction was present in mice with 22q11.2 microdeletion. The abnormal activity patterns are accompanied by weaker synchrony and directed interactions within prefrontal-hippocampal networks. Thus, only severe genetic defects or combined genetic environmental stressors are disruptive enough for reproducing the early network miswiring in mental disorders.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Oberlander, Victoria C; Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Xu, Xiaxia ; Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Chini, Mattia ; Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Hanganu-Opatz, Ileana L; Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Language :
English
Title :
Developmental dysfunction of prefrontal-hippocampal networks in mouse models of mental illness.
ERC - European Research Council DFG - Deutsche Forschungsgemeinschaft
Funding text :
We thank Dr. Joseph Gogos for providing the DISC1+/− and Df(16)A+/− mice and A. Marquardt, P. Putthoff, A. Dahlmann and K. Titze for excellent technical assistance. This work was funded by grants from the European Research Council (ERC-2015-CoG 681577 to I.L.H.-O.) and the German Research Foundation (Ha 4466/10-1, SPP 1665, SFB 936 B5 to I.L.H.-O.).
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