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  1. 1. Effects of 16p11 chromosomal deletion on attention and motivation Jordan Lidsky-Everson Dr. Nicola Grissom, Dr. Teresa Reyes, Dr. Ted Abel
  2. 2. AUTISM IS SEX-SPECIFIC Autism is a sex-specific neurological disorder, affecting males much more commonly than females Multiple studies have found that males display a greater severity of autistic traits
  3. 3. 16P11.2 IS A RISK FACTOR FOR AUTISM Deletions and duplications of the 16p11.2 gene are risk factors for autism spectrum disorder. Horev et al 2011 PNAS
  4. 4. MOUSE MODEL OF 16P11 HEMIDELETION Mice bred on mixed 129/B6 background Horev et al 2011 PNAS
  5. 5. REWARD LEARNING AND MOTIVATION Could some ASD deficits be related to disrupted reward learning or motivation, not decreased preference for rewards? Social interaction deficits and restricted interests and repetitive behaviors are core symptoms of autism.
  6. 6. WHY DOES STRIATAL FUNCTION MATTER? Operant learning (When I see X, I do Y behavior, to cause Z outcome) is dependent on striatal function. DS DS NAc NAc Nucleus accumbens mediates motivation to work for reinforcement Dorsal striatum when I see X, I do Y to get Z
  7. 7. GOAL To characterize male and female 16p11 deleted mice for striatal rule learning and motivation Assess any sex differences
  8. 8. METHODS Food restrict Pavlovian Conditioned Approach Fixed Ratio 1 (center hole) Progressive Ratio 5-Choice Serial Reaction Time Task Transitioned to reversed light/dark cycle Pre-exposure to rewardPreparation Striatal Learning Tasks Attention Tasks
  9. 9. METHODS
  10. 10. METHODS: FIXED RATIO (FR1) 1 response = 1 reward Basic striatal learning action-outcome association DS DS NAc NAc Dorsal striatum when I see X, I do Y, to get Z
  11. 11. 16P11 MALES HAVE STRIATAL DYSFUNCTION Male 16p11del Fixed Ratio 1
  12. 12. METHODS: PROGRESSIVE RATIO (PR) Tests how motivated the animal is to respond DS DS NAc NAc Nucleus accumbens mediates motivation to work for reinforcement
  13. 13. 16P11 MALES HAVE IMPAIRED MOTIVATION
  14. 14. METHODS: SUCROSE PREFERENCE Deficits in operant learning and performance cannot be accounted for by a disliking for sweetened rewards.
  15. 15. RESULTS: FEMALE VULNERABILITY IN STRIATAL LEARNING Male fixed ratio training Female fixed ratio training Effect of Maternal High Fat Diet
  16. 16. CONCLUSION: 16P11 MALE MICE ARE EXTREMELY IMPAIRED DURING OPERANT BEHAVIOR TASKS 16p11.2 male deleted mice are extremely impaired during operant behavior tasks while the females showed no evidence of impairments Future directions: social behavior tasks, social operant tasks, examination of specific genes
  17. 17. ACKNOWLEDGMENTS Dr. Nicola Grissom Dr. Teresa Reyes Dr. Ted Abel Ariel Miller Kevin Hershey Sarah McKee Bob George
  18. 18. REFERENCES Horev G, Ellegood J, Lerch JP, Son YE, Muthuswamy L, Vogel H, et al. Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism. Proc Natl Acad Sci U S A.2011;108:1707617081. Canales, J. J. & Graybiel, A. M. A measure of striatal function predicts motor stereotypy. Nature Neurosci. 3, 377383 (2000)
  19. 19. PR in maternal high fat diet Figure 12: Male progressive ratio training Figure 4: Female progressive ratio task
  20. 20. fem del

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