Abnormal long-range neural synchrony in a maternal immune activation animal model of schizophrenia.
The synchrony of neural firing is believed to underlie the integration of information between and within neural networks in the brain. Abnormal synchronization of neural activity between distal brain regions has been proposed to underlie the core symptomatology in schizophrenia. This study investigated whether abnormal synchronization occurs between the medial prefrontal cortex (mPFC) and the hippocampus (HPC), two brain regions implicated in schizophrenia pathophysiology, using the maternal immune activation (MIA) animal model in rats. This neurodevelopmental model of schizophrenia is induced through a single injection of the synthetic immune system activator polyriboinosinic-polyribocytidylic acid, a synthetic analog of double-stranded RNA, a molecular pattern associated with viral infection, in pregnant rat dams. It is based on epidemiological evidence of increased risk of schizophrenia in adulthood after prenatal exposure to infection. In the present study, EEG coherence and neuronal phase-locking to underlying EEG were measured in freely moving MIA and control offspring. The MIA intervention produced significant reductions in mPFC-HPC EEG coherence that correlated with decreased prepulse inhibition of startle, a measure of sensory gating and a hallmark schizotypal behavioral measure. Furthermore, changes in the synchronization of neuronal firing to the underlying EEG were evident in the theta and low-gamma frequencies. Firing within a putative population of theta-modulated, gamma-entrained mPFC neurons was also reduced in MIA animals. Thus, MIA in rats produces a fundamental disruption in long-range neuronal synchrony in the brains of the adult offspring that models the disruption of synchrony observed in schizophrenia.
Dickerson
Desiree D
DD
Psychology Department, University of Otago, Dunedin 9054, New Zealand.
Wolff
Amy R
AR
Bilkey
David K
DK
D000818:Animals; D000831:Animals, Newborn; D020805:Central Nervous System Viral Diseases / Q000196:embryology / Q000276:immunology* / Q000473:pathology; D003344:Cortical Synchronization; D004195:Disease Models, Animal; D004569:Electroencephalography; D005260:Female; D006624:Hippocampus / Q000196:embryology / Q000276:immunology / Q000821:virology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D009474:Neurons / Q000473:pathology*; D011070:Poly I-C / Q000633:toxicity; D017397:Prefrontal Cortex / Q000196:embryology / Q000276:immunology / Q000821:virology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000276:immunology* / Q000473:pathology / Q000821:virology; D055139:Sensory Gating / Q000276:immunology
D011070:Poly I-C