ESR13. Effect of corticotropin-releasing hormone (CRH) on a thalamic hub for neurodevelopmental disorders

Motivation
Dysfunctions in the thalamocortical system are being increasingly recognized as a circuit endophenotype for neurodevelopmental disorders, such as schizophrenia (SZ) and autism spectrum disorder (ASD), and evidence suggests that the Thalamic Reticular Nucleus (TRN) is a functional hub for thalamocortical network dysfunction.

Research Challenge
Here we will examine the impact of stress and the anxiety-related neuropeptide CRH on the development and function of the TRN, a key element of the thalamocortical system. Endogenous corticotropin-releasing hormone (CRH) inputs to the TRN and the cell-specific localization of the corresponding CRH receptors will be identified through circuit mapping. The effects of CRH on TRN cell excitability will be tested through ex vivo electrophysiology. The impact of CRH on thalamocortical rhythms will be explored through polysomnographic recordings in freely behaving animals combined with gain-/ loss-of-function experiments in which the TRN-projecting CRH-releasing cells will be activated/inhibited. The behavioural concomitants will be assessed in vivo. The expression of SZ- and ASD-related genes in the TRN will be assessed after chronic exposure to CRH or early life stress exposure, and the resulting alterations in TRN cell development and function will be studied. CRH receptor-directed pharmacology will be tested to normalize the CRH-/stress-induced phenotype.

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 (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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