Socio-communicative and Nucleus Accumbens Core Dysfunctions in Fragile X Syndrome
Gabriele GIUA
Team “Sex differences in developmental vulnerability to neuropsychiatric diseases”
Abstract
Fragile X Syndrome (FXS), a predominant inherited intellectual disability and autism-related syndrome, results from FMR1 gene mutation and subsequent FMRP (Fragile X Messenger Ribonucleoprotein 1) deficiency. This deficiency engenders significant central nervous system anomalies, culminating in the cognitive and behavioral disorders of FXS patients. A key area of interest is the complex domain of abnormal emotional processing and socio-communicative challenges, the neurobiological underpinnings of which remain largely uncharted. The nucleus accumbens (NAc) is a pivotal player in reward-related processes that significantly impact emotion, motivation, and social behavior, making it a promising area of investigation. Although NAc spiny projection neurons (SPNs) and associated circuits’ dysfunction aligns with some FXS symptoms, the FMRP deficiency’s precise impact on them is unclear. This thesis aims to explore socio-communicative deficits in an FXS mouse model and examine the NAc’s role in the FXS phenotype. The first objective involves a thorough assessment of socio-communicative deficits in FXS, utilizing deep-learning-based approaches to evaluate both “verbal” and “non-verbal” dimensions. The second objective employs a combination of optogenetics, ex-vivo electrophysiology, and a novel Fmr1-/y::Drd1a-tdTomato mouse model to probe the functionality of accumbal SPN subtypes and their connections in FMRP’s absence. Ultimately, this research sheds light on the socio-behavioral modifications associated with FXS and unveils critical insights into the aberrant NAc functioning, potentially serving as a key neurobiological substrate for FXS symptoms manifestation.
Jury
Serge SCHIFFMAN, Rapporteur – ULB, Brussels
Elodie EY, Rapportrice – IGBMC, Illkirch
Emmanuel VALJENT, Examinateur – IGF, Montpellier
Barbara BARDONI, Présidente du jury – IPMC, Valbonne
Olivier MANZONI, Directeur de thèse – Inmed, Marseille
Tuesday, December 19, 2023 at 2pm – Inmed conference room