Biomedical subjects

Greg I Elmer

Publications and source records attributed to Greg I Elmer.

3 recordsLinked to original sources

PubMed2006

Combined application of behavior genetics and microarray analysis to identify regional expression themes and gene-behavior associations.

In this report we link candidate genes to complex behavioral phenotypes by using a behavior genetics approach. Gene expression signatures were generated for the prefrontal cortex, ventral striatum, temporal lobe, periaqueductal gray, and cerebellum in eight inbred strains from priority group A of the Mouse Phenome Project. Bioinformatic analysis of regionally enriched genes that were conserved across all strains revealed both functional and structural specialization of particular brain regions. For example, genes encoding proteins with demonstrated anti-apoptotic function were over-represented in the cerebellum, whereas genes coding for proteins associated with learning and memory were enriched in the ventral striatum, as defined by the Expression Analysis Systematic Explorer (EASE) application. Association of regional gene expression with behavioral phenotypes was exploited to identify candidate behavioral genes. Phenotypes that were investigated included anxiety, drug-naive and ethanol-induced distance traveled across a grid floor, and seizure susceptibility. Several genes within the glutamatergic signaling pathway (i.e., NMDA/glutamate receptor subunit 2C, calmodulin, solute carrier family 1 member 2, and glutamine synthetase) were identified in a phenotype-dependent and region-specific manner. In addition to supporting evidence in the literature, many of the genes that were identified could be mapped in silico to surrogate behavior-related quantitative trait loci. The approaches and data set described herein serve as a valuable resource to investigate the genetic underpinning of complex behaviors.

Alcoholism↗

PubMed2005

Genotype-environment interactions in mouse behavior: a way out of the problem.

In behavior genetics, behavioral patterns of mouse genotypes, such as inbred strains, crosses, and knockouts, are characterized and compared to associate them with particular gene loci. Such genotype differences, however, are usually established in single-laboratory experiments, and questions have been raised regarding the replicability of the results in other laboratories. A recent multilaboratory experiment found significant laboratory effects and genotype x laboratory interactions even after rigorous standardization, raising the concern that results are idiosyncratic to a particular laboratory. This finding may be regarded by some critics as a serious shortcoming in behavior genetics. A different strategy is offered here: (i) recognize that even after investing much effort in identifying and eliminating causes for laboratory differences, genotype x laboratory interaction is an unavoidable fact of life. (ii) Incorporate this understanding into the statistical analysis of multilaboratory experiments using the mixed model. Such a statistical approach sets a higher benchmark for finding significant genotype differences. (iii) Develop behavioral assays and endpoints that are able to discriminate genetic differences even over the background of the interaction. (iv) Use the publicly available multilaboratory results in single-laboratory experiments. We use software-based strategy for exploring exploration (see) to analyze the open-field behavior in eight genotypes across three laboratories. Our results demonstrate that replicable behavioral measures can be practically established. Even though we address the replicability problem in behavioral genetics, our strategy is also applicable in other areas where concern about replicability has been raised.

Analysis of Variance↗

PubMed2002

Failure of intravenous morphine to serve as an effective instrumental reinforcer in dopamine D2 receptor knock-out mice.

The rewarding effects of opiates are thought to be mediated through dopaminergic mechanisms in the ventral tegmental area, dopamine-independent mechanisms in the nucleus accumbens, or both. The purpose of the present study was to explore the contribution of dopamine to opiate-reinforced behavior using D2 receptor knock-out mice. Wild-type, heterozygous, and D2 knock-out mice were first trained to lever press for water reinforcement and then implanted with intravenous catheters. The ability of intravenously delivered morphine to maintain lever pressing in these mice was studied under two schedules of reinforcement: a fixed ratio 4 (FR4) schedule (saline, 0.1, 0.3, or 1.0 mg/kg, per injection) and a progressive ratio (PR) schedule (1.0 mg/kg, per injection). In the wild-type and heterozygous mice, FR4 behavior maintained by morphine injections was significantly greater than behavior maintained by vehicle injections. Response rate was inversely related to injection dose and increased significantly in the wild-type and heterozygous mice when the animals were placed on the PR schedule. In contrast, the knock-out mice did not respond more for morphine than for saline and did not respond more when increased ratios were required by the PR schedule. Thus, morphine served as a positive reinforcer in the wild-type and heterozygous mice but failed to do so in the knock-out mice. Under this range of doses and response requirements, the rewarding effects of morphine appear to depend critically on an intact D2 receptor system.

Animals↗