Purinergic interference in astrocyte-interneuron communication in social behavior

• Grant number: 22/05894-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: November 27, 2022
• End date: November 26, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Natalia Turrini
• Supervisor: Francesco Papaleo
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Istituto Italiano di Tecnologia (IIT), Italy
• Associated to the scholarship: 20/10725-6 - Evaluation of purinergic receptors in the comorbidity of bipolar disorder and Alzheimer's Disease, BP.DD

Abstract

Socio-cognitive deficits are common features present in several neurodevelopmental and psychiatric disorders, including schizophrenia. However, the brain mechanisms underlying such social dysfunctions are still poorly understood. Recently, the purinergic system has earned attention, and it is known that the role of purinergic signaling in schizophrenia is mostly related to the effects of adenosine and nucleotide receptors on dopaminergic and glutamatergic signaling. Recently, Professor Papaleo's group created novel behavioral tasks enabling to tackle previously unexplored social cognitive functions in mice, distinct from sociability (basic interaction time), social memory, and social reward. This provides an opportunity to investigate the mechanisms regulating distinct social processes, including distinct socio-cognitive processes. The copy number variants 16p11.2 and 22q11.2 hemideletions are well-defined and well-established genetic predisposition factors for neurodevelopmental and psychiatric disorders, both characterized by social deficits, but with qualitative and quantitative differences. The 16p11.2 and 22q11.2 regions are well-conserved between humans and mice, and two mouse lines with a deletion of the syntenic 16p11.2 or 22q11.2 human regions have been reported to recapitulate similar brain dysfunctions as those in human patients. By combining these well-established translational mouse models with newly developed socio-cognitive paradigms, we could disentangle the mechanisms underlying distinct social dysfunctions. We will focus our investigation on microcircuits within the prefrontal cortex (PFC), as this brain structure is suggested to orchestrate different social processes and social brain networks both in humans and mice. (AU)