Neuronal differentiation and brain aging

NRG1 signaling in cortical circuits: insights into the molecular basis of Schizophrenia   

What are the structural and molecular basis of Schizophrenia?

What alterations in neuronal circuits cause the development of this disease?

The heritability of Schizophrenia (SZ), which affects about 1% of the population, is estimated at almost 80%. Neuregulin 1 (NRG1) is a major SZ-risk gene and it controls diverse aspects of neuronal development. We and others previously showed that NRG1 controls neurite extension and regulates excitatory–inhibitory homeostasis in cortical circuits: 1) NRG1 forward signaling via ErbB4 drives the inhibitory feedback of cortical interneurons (Fazzari et al., Nature, 2010); 2) NRG1 intracellular signaling stimulates excitatory transmission and synaptic plasticity. Importantly, we found that excitatory connections depend on the translocation of NRG1 intracellular domain to the nucleus where it regulates gene expression (Fazzari et al., Elife, 2014). Notably, multiple converging evidence in humans and animal models indicates the involvement of NRG1 intracellular signaling in SZ.

Here, we aim to determine the molecular mechanisms downstream of NRG1, specifically focusing on the role of NRG1 signaling in excitatory neurons.

NOTE:

I am a Ramon y Cajal fellow recently integrated in the Lab of Carlos Dotti. This TFM project will be carried out in Dotti's lab under my supervision.