Higher-order Cognitive Processes

The cognitive control of behavior, including the selection and execution of goal-directed actions, is a highly heritable trait and a major determinant of our health and well-being. Alterations in cognitive control are shared common features of different psychiatric and neurodevelopmental disorders such as schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and bipolar disorder. Notably, cognitive deficits in these disorders are currently considered the main source of disability, having the most critical impact on the daily life of the patients and their relatives, on public health and long-term outcomes.


Our first scientific effort is to develop effective preclinical tools to study higher-order cognitive abilities with high translational validity from/to humans, while taking advantage of the outstanding advanced molecular and mechanistic tools available for mice. Importantly, we are interested in how cognitive functions change in males and females throughout development. The domains we are most focused on: working memory, attentional control, executive functions and flexibility.


Related Papers

  1. Leggio GM, Torrisi SA, Mastrogiacomo R, Mauro D, Chisari M, Devroye C, Scheggia D, Nigro M, Geraci F, Pintori N, Giurdanella G, Costa L, Bucolo C, Ferretti V, Sortino MA, Ciranna L, De Luca MA, Mereu M, Managò F, Salomone S, Drago F, Papaleo F*. The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans. Molecular Psychiatry. 2019 Sep 6. doi: 10.1038/s41380-019-0511-4. *Corresponding author
  2. Contarini G, Ferretti V, Papaleo F*. Acute Administration of URB597 Fatty Acid Amide Hydrolase Inhibitor Prevents Attentional Impairments by Distractors in Adolescent Mice. Frontiers in Pharmacology. 2019 Jul 19;10:787. doi: 10.3389/fphar.2019.00787.
  3. Morè L, Lauterborn JC, Papaleo F*, Brambilla R. Enhancing cognition through pharmacological and environmental interventions: examples from preclinical models of neurodevelopmental disorders. Neurosci Biobehav Rev. 2019 Apr 10. doi: 10.1016/j.neubiorev.2019.02.003. [Epub ahead of print] Review. *Corresponding author.
  4. Scheggia D, Mastrogiacomo R, Mereu M, Sannino S, Straub RE, Armando M, Managò F, Guadagna S, Piras F, Zhang F, Kleinman JE, Hyde TM, Kaalund SS, Pontillo M, Orso G, Caltagirone C, Borrelli E, De Luca MA, Vicari S, Weinberger DR, Spalletta G, Papaleo F*. Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment. Nature Communications. 2018 Jun 11;9(1):2265. doi:10.1038/s41467-018-04711-w. *Corresponding author.
  5. Carr GV, Maltese F, Sibley DR, Weinberger DR, Papaleo F*. The Dopamine D5 Receptor Is Involved in Working Memory. Frontiers in Pharmacology. 2017. Oct 6;8:666. doi: 10.3389/fphar.2017.00666. *Corresponding author.
  6. Ciampoli M, Contarini G, Mereu M, Papaleo F*. Attentional Control in Adolescent Mice Assessed with a Modified Five Choice Serial Reaction Time Task. Scientific Reports. 2017 Aug 30;7(1):9936. doi: 10.1038/s41598-017-10112-8. *Corresponding author.
  7. Scheggia D, Zamberletti E, Realini N, Mereu M, Contarini G, Ferretti V, Managò F, Margiani G, Brunoro R, Rubino T, De Luca MA, Piomelli D, Parolaro D, Papaleo F*. Remote memories are enhanced by COMT activity through dysregulation of the endocannabinoid system in the prefrontal cortex. Molecular Psychiatry. 2018 Apr;23(4):1040-1050. doi:10.1038/mp.2017.126. Epub 2017 Jun20. *Corresponding author.
  8. Sannino S, Padula MC, Managò F, Schaer M, Schneider M, Armando M, Scariati E, Sloan-Bena F, Mereu M, Pontillo M, Vicari S, Contarini G, Chiabrera C, Pagani M, Gozzi A, Eliez S, Papaleo F*. Adolescence is the starting point of sex-dichotomous COMT genetic effects. Transl Psychiatry. 2017 May 30;7(5):e1141. doi: 10.1038/tp.2017.109. *Corresponding author.
  9. Mereu M, Contarini G, Buonaguro EF, Latte G, Managò F, Iasevoli F, de Bartolomeis A, Papaleo F*. Dopamine transporter (DAT) genetic hypofunction in mice produces alterations consistent with ADHD but not schizophrenia or bipolar disorder. Neuropharmacology. 2017 Jul 15;121:179-194. doi:10.1016/j.neuropharm.2017.04.037. Epub 2017 Apr 26. *Corresponding author.
  10. Huang H, Guadagna S, Mereu M, Ciampoli M, Pruzzo G, Ballard T, Papaleo F*. A schizophrenia relevant 5-Choice Serial Reaction Time Task for mice assessing broad monitoring, distractibility and impulsivity. Psychopharmacology (Berl). 2017 Jul;234(13):2047-2062. doi:10.1007/s00213-017-4611-z. Epub 2017 Apr 5. *Corresponding author.
  11. Managò F, Mereu M, Mastwal S, Mastrogiacomo R, Scheggia D, Emanuele M, De Luca MA, Weinberger DR, Wang KH, Papaleo F*. Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia. Cell Rep. 2016 Aug 23;16(8):2116-28. doi: 10.1016/j.celrep.2016.07.044. *Corresponding author.
  12. Carr GV, Chen J, Yang F, Ren M, Yuan P, Tian Q, Bebensee A, Zhang GY, Du J, Glineburg P, Xun R, Akhile O, Akuma D, Pickel J, Barrow JC, Papaleo F, Weinberger DR. KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia. Molecular Psychiatry. 2016 Nov;21(11):1517-1526. doi: 10.1038/mp.2015.219.
  13. Papaleo F, Yang F, Paterson C, Palumbo S, Carr GV, Wang Y, Floyd K, Huang W, Thomas CJ, Chen J, Weinberger DR, Law AJ. Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model. J Neurosci. 2016 Apr 27;36(17):4859-75. doi: 10.1523/JNEUROSCI.4632-15.2016.
  14. Scheggia D, Papaleo F*. An Operant Intra-/Extra-dimensional Set-shift Task for Mice. J Vis Exp. 2016 Jan 22;(107). doi: 10.3791/53503. *Corresponding author.
  15. Papaleo F*, Sannino S, Piras F, Spalletta G. Sex-dichotomous effects of functional COMT genetic variations on cognitive functions disappear after menopause in both health and schizophrenia. Eur Neuropsychopharmacol. 2015 Dec;25(12):2349-63. doi: 10.1016/j.euroneuro.2015.10.005. *Corresponding author.
  16. Sannino S, Gozzi A, Cerasa A, Piras F, Scheggia D, Manago F, Damiano M, Galbusera A, Erickson LC, Tonelli DDT, Bifone A, Tsaftaris SA, Caltagirone C, Weinberger DR, Spalletta G, Papaleo F*COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and Humans. Cerebral Cortex 2015; Sep;25(9):2529-41. doi: 10.1093/cercor/bhu053. Epub 2014 Mar 21. *Corresponding author.
  17. Papaleo F*, Burdick MC, Callicott JH, Weinberger DR. Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans. Molecular Psychiatry. 2014 Mar;19(3):311-6. doi: 10.1038/mp.2013.133. Epub 2013 Oct 22. *Corresponding author.
  18. Scheggia D, Bebensee A, Weinberger DR, Papaleo F*. The Ultimate Intra/Extradimensional Attentional Set-Shifting Task for Mice. Biol Psychiatry. 2014 Apr 15;75(8):660-70. doi: 10.1016/j.biopsych.2013.05.021. Epub 2013 Jun 28. *Corresponding author.
  19. Carr GV, Jenkins KA, Weinberger DR, Papaleo F*. Loss of dysbindin-1 in mice impairs reward-based operant learning by increasing impulsive and compulsive behavior. Behav Brain Res. 2013 Mar 15;241:173-84. doi: 10.1016/j.bbr.2012.12.021. Epub 2012 Dec 20. *Corresponding author.
  20. Papaleo F*, Erickson L, Liu G, Chen J, Weinberger DR. Effects of sex and COMT genotype on environmentally modulated cognitive control in mice. PNAS. 2012 Dec 4;109(49):20160-5. doi: 10.1073/pnas.1214397109. Epub 2012 Nov 19. *Corresponding author.
  21. Papaleo F*, Yang F, Garcia S, Chen J, Lu B, Crawley JN, Weinberger DR. Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Molecular Psychiatry 2012 Jan; 17(1):85-98. doi: 10.1038/mp.2010.106. Epub 2010 Oct 19. *Corresponding author.
  22. Papaleo F*, Silverman JL, Aney J, Tian Q, Barkan CL, Chadman KK, Crawley JN. Working memory deficits, increased anxiety-like traits and seizure susceptibility in BDNF overexpressing mice. Learning & Memory. 2011 Jul 26;18(8):534-44. Print 2011 Aug. *Corresponding author.
  23. Papaleo F*, Lipska BK, Weinberger DR. Mouse models of genetic effects on cognition: Relevance to schizophrenia. Neuropharmacology. 2012 Mar;62(3):1204-20. Epub 2011 May 5.*Corresponding author.
  24. Papaleo F, Crawley JN, Song J, Lipska BK, Pickel J, Weinberger DR, Chen J. Genetic dissection of the role of Catechol-O-Methyltransferase in cognition and stress reactivity in mice. J. Neurosci. 2008 Aug 27; 28(35):8709-23. doi: 10.1523/JNEUROSCI.2077-08.2008.