Alessandro Chioino. Role of Mitofusins in neurodevelopmental trajectories of psychopathology

Motivation
Emerging evidence points to a critical role of mitochondrial dysfunctions in the pathophysiology of psychiatric disorders, including anxiety and depression, but the mechanisms mediating mitochondrial effects remain understudied. Recent findings highlight reduced brain expression of the mitochondrial GTPase Mitofusins 1 and 2 (Mfn1 and Mfn2; molecules critically involved in mitochondrial fusion and other functions) in depression and stress-related psychopathologies.

Research Challenge
The nucleus accumbens is a critical hub for motivated behavior and its function is altered in anxiety and depression. This project will use mouse genetics and gene delivery to examine the contribution of Mfn deficiency in specific accumbal medium spinal neurons for the production of motivated behaviors related to anxiety and depression. Fiber photometry will be applied to identify target brain regions involved, and optogenetic approaches to establish the causal involvement of specific projection neurons. The impact of Mfn deficiency in specific cell types for E/I balance will be monitored in vivo and its synaptic consequences in vitro. The final goal is to identify the circuitry engaged in dysfunctional behaviors produced by impaired mitochondrial dynamics in specific nucleus accumbens neurons and uncover relevant treatment targets for neuropsychiatric alterations.

Professor Carmen Sandi‘s laboratory at the Brain Mind Institute (BMI-EPFL) investigates the impact and mechanisms whereby stress and personality affect brain function and behavior, with a focus on the social domain and, particularly, on aggression and social hierarchies.

Requirements
General Requirements apply.

Supervision and Secondments
The PhD project will be carried out in Carmen Sandi’s Laboratory of Behavioral Genetics at EPFL. The ESR will enrol in the EPFL PhD program in Neuroscience (EDNE).  The project also features secondments (extended stays) at IINS-CNRS (Laurent Groc) and ICL (Thomas Knöpfel).

Supervisor(s): Carmen Sandi (carmen.sandi@epfl.ch), Simone Astori (simone.astori@epfl.ch)

Host Location: Brain Mind Institute (BMI), EPFL, Lausanne, Switzerland.

 

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