Quantifying Individual Variation in the Propensity to Attribute Incentive Salience to Reward Cues

If reward-associated cues acquire the properties of incentive stimuli they can come to powerfully control behavior, and potentially promote maladaptive behavior. Pavlovian incentive stimuli are defined as stimuli that have three fundamental properties: they are attractive, they are themselves desired, and they can spur instrumental actions. We have found, however, that there is considerable individual variation in the extent to which animals attribute Pavlovian incentive motivational properties (“incentive salience”) to reward cues. The purpose of this paper was to develop criteria for identifying and classifying individuals based on their propensity to attribute incentive salience to reward cues. To do this, we conducted a meta-analysis of a large sample of rats (N = 1,878) subjected to a classic Pavlovian conditioning procedure. We then used the propensity of animals to approach a cue predictive of reward (one index of the extent to which the cue was attributed with incentive salience), to characterize two behavioral phenotypes in this population: animals that approached the cue (“sign-trackers”) vs. others that approached the location of reward delivery (“goal-trackers”). This variation in Pavlovian approach behavior predicted other behavioral indices of the propensity to attribute incentive salience to reward cues. Thus, the procedures reported here should be useful for making comparisons across studies and for assessing individual variation in incentive salience attribution in small samples of the population, or even for classifying single animals

Histone H2A (H2A.X and H2A.Z) Variants in Molluscs: Molecular Characterization and Potential Implications For Chromatin Dynamics

Histone variants are used by the cell to build specialized nucleosomes, replacing canonical histones and generating functionally specialized chromatin domains. Among many other processes, the specialization imparted by histone H2A (H2A.X and H2A.Z) variants to the nucleosome core particle constitutes the earliest response to DNA damage in the cell. Consequently, chromatin-based genotoxicity tests have been developed in those cases where enough information pertaining chromatin structure and dynamics is available (i.e., human and mouse). However, detailed chromatin knowledge is almost absent in most organisms, specially protostome animals. Molluscs (which represent sentinel organisms for the study of pollution) are not an exception to this lack of knowledge. In the present work we first identified the existence of functionally differentiated histone H2A.X and H2A.Z variants in the mussel Mytilus galloprovincialis (MgH2A.X and MgH2A.Z), a marine organism widely used in biomonitoring programs. Our results support the functional specialization of these variants based on: a) their active expression in different tissues, as revealed by the isolation of native MgH2A.X and MgH2A.Z proteins in gonad and hepatopancreas; b) the evolutionary conservation of different residues encompassing functional relevance; and c) their ability to confer specialization to nucleosomes, as revealed by nucleosome reconstitution experiments using recombinant MgH2A.X and MgH2A.Z histones. Given the seminal role of these variants in maintaining genomic integrity and regulating gene expression, their preliminary characterization opens up new potential applications for the future development of chromatin-based genotoxicity tests in pollution biomonitoring programs

The distribution of PCA Scores across each of the 5 days of Pavlovian training, using the formula given in Table 1.

<p>The number of rats are binned according to their PCA Scores, which ranges from +1 to −1, with 0.1 bin sizes. The PCA Scores range from +1 to −1. Thus, the vertical axis shows the number of rats in each bin, and the horizontal axis the PCA Score. Note that PCA Score reveals two subpopulations of animals by Days 4 and 5 of training.</p

The PCA Score is strongly correlated with lever- and food cup-directed behavior on the final day of training.

<p>Selected scatterplots of correlations reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038987#pone-0038987-t002" target="_blank">Table 2</a> are shown. Each symbol represents an individual animal. The top panels show the number of lever contacts plotted as a function of the PCA Score on Day 1 (A) and Day 5 (B) of Pavlovian training. The bottom panels show the number of head entries into the food cup, during the 8 s CS period (during which time the lever was inserted into the chamber), plotted as a function of the PCA Score on Day 1 (C) and Day 5 (D) of training.</p

Correlations between Lever Contacts, CS Food Cup Entries, Inter-trial Interval (ITI) Food Cup Entries, and the PCA Scores on Day 1 (top) and Day 5 (bottom) of Pavlovian training.

<p>Legend: Numbers indicate Pearson's correlation coefficient (r) and those that are Italicized numbers indicate statistically significant correlations (ps<0.01) are italicized. The number inside parentheses denotes the day of Pavlovian training.</p

Variation in the topography of the conditioned response from trial to trial as a function of PCA Index Score.

<p>This analysis is based on a subset (n = 370) of the total sample of animals. Behavioral responses on a given trial were classed as: (1) ONLY trials (a trial in which a rat made only one or more lever deflections or only one or more food cup entries during the CS period, but not both); (2) BOTH trials (a trial in which an animal made at least one lever deflection and one food cup entry in the same 8-s CS period); (3) NONE trials (trials in which there was neither a lever deflection nor a food cup entry). Panels A and B show the percent of ONLY and BOTH trials for each rat, respectively, plotted as a function of the animal's PCA Index Score. Based on these data we classed the animals as sign-trackers (STs; a PCA Index Score of 0.5 or above), goal-trackers (GTs; a score of −0.5 or less), or intermediates (INs; scores from −0.49 to +0.49). Panel C shows the proportion of ONLY, BOTH, and NONE trials for STs, INs, and GTs. Panel D shows a more detailed analysis of the Intermediates. The INs are subdivided into those with positive vs. negative PCA Index Scores. This does not have much effect of the percent of ONLY, BOTH or NONE trials, but the inset shows that INs with positive scores (towards sign-tracking) typically press the lever on ONLY trials, and those with negative PCA Index Scores typically make food cup entries.</p

Mean ± SEM number of lever deflections (A) or food cup entries (B), probability of approaching the lever (C) or food cup (D) during the CS period, and latency to contact the lever (E) or make a food cup entry (F) during the CS period, over 5 days of Pavlovian training in 1,878 rats classed as STs, GTs or INs, as described in Fig. 6.

<p>Note that the SEM is smaller than the symbol in most cases.</p