A selective role for dopamine in stimulus-reward learning

Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, becoming attractive and desirable incentive stimuli. However, whether a cue acts solely as a predictor of reward, or also serves as an incentive stimulus, differs between individuals. Thus, individuals vary in the degree to which cues bias choice and potentially promote maladaptive behaviour. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of stimulus-reward learning in which incentive salience is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behaviour. This work provides insight into the neurobiology of a form of stimulus-reward learning that confers increased susceptibility to disorders of impulse control.     

Multiple neonatal deaths due to a homoplasmic mitochondrial DNA mutation.

Mutations of mitochondrial DNA (mtDNA) are an important cause of genetic disease. We describe a family with an unusual homoplasmic mutation that resulted in six neonatal deaths and one surviving child with Leigh syndrome. The mother is clinically normal, but a severe biochemical and molecular genetic defect was present in both a fatally affected child and the mother. This family highlights the role of homoplasmic mt-tRNA mutations in genetic disease.     

The identification of liquid ethane in Titan's Ontario Lacus

Titan was once thought to have global oceans of light hydrocarbons on its surface, but after 40 close flybys of Titan by the Cassini spacecraft, it has become clear that no such oceans exist. There are, however, features similar to terrestrial lakes and seas, and widespread evidence for fluvial erosion, presumably driven by precipitation of liquid methane from Titan's dense, nitrogen-dominated atmosphere. Here we report infrared spectroscopic data, obtained by the Visual and Infrared Mapping Spectrometer (VIMS) on board the Cassini spacecraft, that strongly indicate that ethane, probably in liquid solution with methane, nitrogen and other low-molecular-mass hydrocarbons, is contained within Titan's Ontario Lacus.     

HITS-CLIP yields genome-wide insights into brain alternative RNA processing

Protein-RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.     

Proportionally more deleterious genetic variation in European than in African populations

Quantifying the number of deleterious mutations per diploid human genome is of crucial concern to both evolutionary and medical geneticists. Here we combine genome-wide polymorphism data from PCR-based exon resequencing, comparative genomic data across mammalian species, and protein structure predictions to estimate the number of functionally consequential single-nucleotide polymorphisms (SNPs) carried by each of 15 African American (AA) and 20 European American (EA) individuals. We find that AAs show significantly higher levels of nucleotide heterozygosity than do EAs for all categories of functional SNPs considered, including synonymous, non-synonymous, predicted 'benign', predicted 'possibly damaging' and predicted 'probably damaging' SNPs. This result is wholly consistent with previous work showing higher overall levels of nucleotide variation in African populations than in Europeans. EA individuals, in contrast, have significantly more genotypes homozygous for the derived allele at synonymous and non-synonymous SNPs and for the damaging allele at 'probably damaging' SNPs than AAs do. For SNPs segregating only in one population or the other, the proportion of non-synonymous SNPs is significantly higher in the EA sample (55.4%) than in the AA sample (47.0%; P < 2.3 x 10(-37)). We observe a similar proportional excess of SNPs that are inferred to be 'probably damaging' (15.9% in EA; 12.1% in AA; P < 3.3 x 10(-11)). Using extensive simulations, we show that this excess proportion of segregating damaging alleles in Europeans is probably a consequence of a bottleneck that Europeans experienced at about the time of the migration out of Africa.     

Some spatial and behavioral features of the thirteen-lined ground squirrel

Some relationships between home range, agonistic behavior, and reproductive patterns in thirteen-lined ground squirrels were investigated in Laramie Plains, Wyoming (August 1966&ndash;April 1969). Population size and densities fluctuated seasonally and annually. Adult male (N = 7) home ranges averaged 0.24 ha and were smaller than those of the female (N = 9), which averaged 0.35 ha. Agonistic interactions were more frequent during the natal period (late May&ndash;June) than during the breeding-gestation period (mid April&ndash;May). Most squirrels (86 percent) shared capture sites and had overlapping home ranges. However, a certain degree of spacing existed because of agonistic behavior.     

Use of agricultural lands by San Joaquin kit foxes

Although the current range of the endangered San Joaquin kit fox ( Vulpes macrotis mutica ) borders large areas of farmland, the ecology of this species rarely has been studied within an agricultural setting. In central California, we examined habitat use, prey availability, and diet of radio-collared kit foxes inhabiting an aqueduct right-of-way (ROW) bordered by farmland. During both years of study (1998–1999), nocturnal locations of foxes occurred more often than expected (based on habitat availability) in the ROW and less often than expected within annual crops. Orchards were used disproportionately more than their availability during 1998 and were used in proportion to availability during 1999. Kit foxes traveled up to 1.1 km into annual crops and up to 1.5 km into orchards. Among diurnal locations (den sites) of foxes, 98% were within the ROW. Live-trapping revealed higher densities and greater diversity of rodents along the ROW than within farmland. Remains of murid rodents were found in 79% of kit fox scats. Our findings indicated that kit foxes ranged into orchards and annual croplands at night, but almost never occupied these areas during the day. The lack of den sites and low prey availability within farmland probably limited the ability of kit foxes to exploit and occupy these areas. Providing artificial den sites within croplands (especially within orchards) and along canals may increase use of farmland by kit foxes and facilitate their movement between isolated patches of natural lands.