Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization.

Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI.

Aberrant neural synchrony in the maternal immune activation model: using translatable measures to explore targeted interventions.

Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia.

Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin.

The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINS(C96Y)) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area).

Clozapine administration ameliorates disrupted long-range synchrony in a neurodevelopmental animal model of schizophrenia.

The abnormal synchronisation of neural networks may underlie some of the deficits observed in schizophrenia. Abnormal synchronisation can be induced in animal models. We investigated whether acute clozapine treatment might function therapeutically by ameliorating the deficit in theta frequency coherence between the prefrontal cortex and the hippocampus that is induced in rats exposed to maternal immune activation (MIA)--a risk-factor for schizophrenia.

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.