Modeling increased density of D2 receptors in the striatum of the mouse

Increased striatal D2 receptor activation may account for the positive symptoms that can be treated with selective D2 receptor antagonists. Nevertheless, a causal relationship between increased D2 receptor activation and the appearance of symptoms is difficult to draw, simply because too many other factors are changed in the brain of patients with schizophrenia. To directly study the behavioral consequences of increased striatal D2 receptor density that has been observed in the imaging studies,...

Spatial aspects of SZ etiology andor pathophysiology

Mouse Brain Stereotaxic Coordinates

The precise brain regions and related neural circuits involved in SZ remain to be elucidated. In recent years, various lines of study have detected structural and functional changes in some brain areas in SZ. Postmortem studies, although many of them have conflicting results, have suggested that there is no gliosis and no cell death, but there are differing accounts of reduced grey matter volume in such regions as the right basal ganglia, right prefrontal cortex, right insular cortex, right...

Yoichi Gondo and Ryutaro Fukumura

RIKEN BioResource Center, Tsukuba, Ibaraki, Japan Abstract By the N-ethyl-N-nitrosourea (ENU)-based gene-driven mutagenesis, it is now possible to obtain allelic series of mutant mouse strains, each of which carries a different base substitution in any target gene. This new reverse genetic tool has become available based on the ENU mutant mouse library. The ENU mutant mouse library consists of dual archives of frozen sperm and corresponding genomic DNA derived from Generation-1 (G1) male mice,...

NR1KD as a representative model of NMDA receptor hypofunction

In the past decade the number of genetic mouse models of NMDA receptor hypofunction have steadily increased, which should not be surprising considering the many ways that NMDA receptors can be regulated. A recent review highlights the several examples of mice with targeted mutations in the genes encoding glutamate receptors (Inta et al., 2009) many of these have overlapping phenotypes with the NR1-KD mice or with each other that underscore the common consequences of NMDA receptor dysfunction or...

The utility of AAV vectors in modeling schizophrenia susceptibility

Understanding the pathophysiology of genetic polymorphisms that effect risk for psychiatric disease is challenging. Although simple model systems play an important role (Reinke and White, 2002 Davis, 2004), psychiatric disorders such as schizophrenia appear to involve complex changes in higher brain circuits (Lewis and Sweet, 2009), necessitating the study of higher mammalian species and NHPs in particular. Unfortunately, NHPs are not easily subject to genetic investigation due to a long...

DISC1 analyses in flies

Disrupted-In-Schizophrenia-1 (DISC1) is a promising genetic factor for a wide range of mental illnesses, including schizophrenia, bipolar disorder, major depression, and autism spectrum conditions (Harrison and Weinberger, 2005 Ishizuka et al., 2006 Chubb et al., 2008 Kilpinen et al., 2008 Jaaro-Peled et al., 2009). DISC1 was originally identified as the gene located on chromosome 1 and interrupted by a balanced translocation t(1q42.1 11q14.3) that is linked to psychopathology including...

Behavioral pharmacology of NR1KD mice

The characterization of NR1-KD behavioral pharmacology provides information on the status of neurotransmitter systems, and also lends support for the utility of the model in the discovery of novel antipsychotics. As with MK-801-treated mice, some of the behavioral abnormalities of NR1-KD mice can be ameliorated to varying degrees with antipsychotics or psychoac-tive drugs. Locomotor activity in NR1-KD mice is higher than wild-type mice this is due to a failure to habituate to novel environment...

Zebrafish as a model to study behavior

Schizophrenia is characterized by a multitude of positive and negative symptoms including hallucinations, delusions and social withdrawal as well as cognitive deficits (Lewis and Lieber-man, 2000 Harvey et al., 2002). In the field of schizophrenia research, the mouse is typically used as a model to study the behavioral abnormalities seen in schizophrenia including deficits in working memory, impaired sensory motor gating and increased activity hyperloco-motion (Lipska and Weinberger, 2000...

The greatly increased complexity of primate PFC neurons

The pyramidal cells of the PFC also have an expanded dendritic architecture to support their numerous connections, and have about 70 more spines than the pyramidal cells of the primary sensory or motor cortices (Jacobs et al., 2001). Elston et al. (2006) have written that the highly branched, spinous neurons in the human granular PFC may be a key component of human intelligence. Similarly, the pyramidal neurons in monkey dorsolateral PFC, which subserve recurrent network connections, have...