Differential processing of delay versus uncertainty in male but not female 16p11.2 hemideletion mice

Abstract

Neurodevelopmental disorders are associated with differences in learning and motivation that can influence executive function, including behavioral flexibility and decision making. 16p11.2 hemideletion is a chromosomal copy number variant that is linked to neurodevelopmental disorders. 16p11.2 hemideletion in mice has been previously found to produce male-biased changes in reward learning, but the link between this and altered flexible decision making is poorly understood. We challenged 16p11.2 hemideletion mice with two reward-guided decision making tasks assessing flexible decision making under cost, delay and probability discounting. Both tasks elicited long-term changes in flexible decision making that separated 16p11.2 hemideletion males from wildtype males. In delay discounting,16p11.2 hemideletion males had a stronger, less flexible preference for the large reward at long delays, and this effect was reduced as wildtype males adjusted their preference to match that of the hemideletion males. In probability discounting, 16p11.2 hemideletion males initially had a similar preference for seeking improbable large rewards as did wildtype males, but over time began to prefer certainty to a greater extent than did wildtype males. Female mice discounted similarly for delayed or risky rewards regardless of the presence of the copy number variant. We have previously seen that male 16p11.2 hemideletion mice commit fewer nonreinforced responses than male wildtype mice in an operant setting, which we replicate here in delay discounting, while the introduction of risky rewards eliminates genotype differences in nonreinforced responses. Overall these data suggest that 16p11.2 hemideletion in males leads to differential processing of costs of delay versus inconsistency, with greater aversion to uncertainty than delays, and greater behavioral control by cues that consistently predict an outcome.