A Sensitive Homecage-Based Novel Object Recognition Task for Rodents

The recognition of novel objects is a common cognitive test for rodents, but current paradigms have limitations, such as low sensitivity, possible odor confounds and stress due to being performed outside of the homecage. We have developed a paradigm that takes place in the homecage and utilizes four stimuli per trial, to increase sensitivity. Odor confounds are eliminated because stimuli consist of inexpensive, machined wooden beads purchased in bulk, so each experimental animal has its own set of stimuli. This paradigm consists of three steps. In Step 1, the sampling phase, animals freely explore familiar objects (FO). Novel Objects (NO1 and NO2) are soiled with bedding from the homecage, to acquire odor cues identical to those of the FO. Steps 2 and 3 are test phases. Herein we report results of this paradigm from neurologically intact adult rats and mice of both sexes. Identical procedures were used for both species, except that the stimuli used for the mice were smaller. As expected in Step 2 (NO1 test phase), male and female rats and mice explored NO1 significantly more than FO. In Step 3 (NO2 test phase), rats of both sexes demonstrated a preference for NO2, while this was seen only in female mice. These results indicate robust novelty recognition during Steps 2 and 3 in rats. In mice, this was reliably seen only in Step 2, indicating that Step 3 was difficult for them under the given parameters. This paradigm provides flexibility in that length of the sampling phase, and the delay between test and sampling phases can be adjusted, to tailor task difficulty to the model being tested. In sum, this novel object recognition test is simple to perform, requires no expensive supplies or equipment, is conducted in the homecage (reducing stress), eliminates odor confounds, utilizes 4 stimuli to increase sensitivity, can be performed in both rats and mice, and is highly flexible, as sampling phase and the delay between steps can be adjusted to tailor task difficulty. Collectively, these results indicate that this paradigm can be used to quantify novel object recognition across sex and species

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Role of Pre-Synaptic Munc 13-1 in Voluntary Ethanol Consumption and Tolerance

In the United States alone, approximately 18 million people suffer from alcohol use disorders. The role of the munc 13-1 pre-synaptic protein in alcohol-related behaviors has been little-studied, despite being a known site for ethanol binding. Munc 13-1 is an active zone protein that is vital for vesicle maturation at the synapse. Mice that are heterozygous for the gene regulating munc 13-1 produce synapses that, while structurally sound, show an approximate 50% decrease in this protein. Ethanol binds munc 13-1, decreasing its functional ability and likely antagonizing glutamatergic targets. Exposure to NMDA receptor antagonists has long been known to increase hippocampal neurogenesis, and it is likely that mice with inherently deficient NMDA stimulation would show the same pro-neurogenic outcomes. The current study aimed to perform a thorough behavioral analysis of mice heterozygous for munc 13-1. Few phenotypes have been identified in this specific type of mouse, and genetically engineered mice may express very different phenotypes from mutation to mutation. This project also endeavored to assess how loss of munc 13-1 affects voluntary binge and chronic alcohol consumption. Separately, munc 13-1 heterozygotes were evaluated for changes to acute functional tolerance following an injection of a standardized dose alcohol, using an accelerating rotarod as a measure of motor coordination. The last goal of the current project was to compare levels of doublecortin (DCX)-positive cells in the dentate gyrus between alcohol-exposed and alcohol-naïve mice, and also compare DCX levels across wildtype and heterozygous mice. Taken together, these results will give future researchers a better understanding of the role that pre-synaptic protein munc 13-1 plays in alcohol consumption and tolerance.Psychology, Department o