A novel multidimensional reinforcement task in mice elucidates sex-specific behavioral strategies

BackgroundSex is a critical biological variable in the neuropathology of psychiatric disease, and in many cases, women represent a vulnerable population. It has been hypothesized that sex differences in neuropsychiatric disorders are manifestations of differences in basic reward processing. However, preclinical models often present rewards in isolation, ignoring that ethologically, reward seeking requires the consideration of potential aversive outcomes.MethodsWe developed a Multidimensional Cue Outcome Action Task (MCOAT) to dissociate motivated action from cue learning and valence. Mice are trained in a series of operant tasks. In phase 1, mice acquire positive and negative reinforcement in the presence of discrete discriminative stimuli. In phase 2, both discriminative stimuli are presented concurrently allowing us to parse innate behavioral strategies based on reward seeking and shock avoidance. Phase 3 is punished responding where a discriminative stimulus predicts that nose-poking for sucrose occurs concurrently with footshock, allowing for the assessment of how positive and negative outcomes are relatively valued.ResultsFemales prioritize avoidance of negative outcomes over seeking positive, while males have the opposite strategy. In cases where rules are uncertain, males and females employ different strategies, with females demonstrating bias for shock avoidance.ConclusionsThe MCOAT has broad utility for neuroscience research where pairing this task with recording and manipulation techniques will allow for the definition of the discrete information encoded within cellular populations. Ultimately, we show that making conclusions from unidimensional data leads to inaccurate generalizations about sex-specific behaviors that do not accurately represent ground truth.

Hedonics and the “Selective Associations” Biological Constraint on Learning

Research concerned with visual dominance in appetitive and auditory dominance in aversive learning situations (selective associations) is reviewed. The present analysis stresses that the dominant sensory modality of stimulus control is determined by the relative affective valence acquired by a compound auditory-visual stimulus through reinforcement contingencies, rather than by whether the primary reinforcer is appetitive or aversive. For example, take two groups of rats or pigeons on exactly the same shock-avoidance contingency in a tone-light compound (TL), but with different contingencies when the compound is absent (TL). Responding came predominantly under (1) auditory control when conditions in TL were hedonically negative relative to those in (TL), and (2) visual control when conditions in (TL) made TL relatively positive. Selective associations here are a product of the relative hedonic state, positive or negative, established to the auditory-visual compound. Therefore, this constraint reflects a high level of functioning by a hedonic comparator -- with TL’s hedonic value contextually determined by the totality of the events encountered, and reinforcement contingencies, operating in its world. The physical particulars of the reinforcer in TL here, shock avoidance, clearly were not responsible for the hedonic psychological state TL produced. Weiss, Panlilio, and Schindler (1993a, 1993b) went on to show that these proclivities can be (1) reversed, and (2) overcome by a blocking design when the biologically-contingency-disadvantaged stimulus is first pretrained on its own. Relating the “hedonic model” to evolution is speculative. But, the hedonic model is scientifically integrative by relating this biological constraint to a variety of phenomena that involve incentive-motivational states. These include choice behavior, conditioned preference, behavioral contrast and appetitive-aversive interactions.