טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentHazan Yael
SubjectWhen Environment Demands Meet the Genes: Behavioral,
Molecular and Physiological Aspects of a Rat Model
for Social Cooperation
DepartmentDepartment of Medicine
Supervisor Dr. Avraham Avital
Full Thesis textFull thesis text - English Version


Abstract

Social cooperation behavior is a widespread phenomenon in pairs or large groups aimed to achieve a tangible, immediate reward, by voluntary joint action. When collaborating in such social activity, each participant needs to learn to adjust the individual actions by using cues from the presence and/or behaviors of others. Thus, cooperative behavior is a complex executive function that requires various social cognitive skills. Impairment in social cooperation was reported in several neuro- psychopathologies, including autism spectrum disorder, bipolar disorder, obsessive-compulsive disorder and schizophrenia. A suggested reason for lack of significant treatments for most of the above-mentioned pathologies, is the fact that the available therapies are not well-informed by ethological mechanisms and neurocircuitry models, which also reflect the lack of valid animal models. Thus, developing neurobiologically guided treatments of impaired social cooperation based on a well-studied mechanism, could be highly cost-effective to cope with future socially-impaired brain pathologies. Recently, our lab has established a fully automated cooperation maze, allowing us to address the question of the nature vs. nurture basis of social cooperation behavior. Implementing a selective inbreeding procedure, following 10 generations, we were able to progressively show a difference between two subpopulations of 'high' performers (HPR) and 'low' performers (LPR) in social cooperation test. We concluded that the increased frequency of cooperative behavior in the two sub populations suggest a genetic component of these two phenotypes and strengthens the predictive and face validity of our cooperation maze. Secondly, we aimed to identify the interplay between hereditary and environmental influences on social cooperation behavior. This aim was addressed by combining transgenerational selective inbreeding and in- or cross- foster mothering experiments. We found that the inheritability of social cooperation can be predictable based on parental origin rather than on environmental influences. Exploring the mechanism, we assessed protein expression profiles (by proteomics) in the two subpopulations and identified expression changes of proteins in the HPR/LPR rats in 3 different brain areas related to social cooperation. To further investigate this difference, we examined mRNA expression and found a distinct profile between the well-established extreme subpopulations that follows the inheritance along generations. Examining the ‘social hormone’ Oxytocin, we found that it is required for social cooperation but neither its circulating level nor its receptor expression did not differentiate between HPR/LPR.

The study provides evidence for the inheritance of social cooperation that is significantly explained by genetic rather than environmental factors. The inherited selection of the HPR/LPR is supported by protein profile that yielded several proteins that will serve as targets for modulating social cooperation. The behavioral, molecular and physiological findings contributed to our understanding 2


of social cooperation behavior and may also better our investigation of socially-impaired psychopathologies such as Autism spectrum disorder.