QBI Neuroscience Seminar: Glutamatergic circuits in stress susceptibility: pathway specificity and transcriptional mechanisms

Event Details

Date:

Friday, 18 December 2015

Time:

12:00 pm - 1:00 pm

Room:

QBI Level 7 Auditorium

UQ Location:

Queensland Brain Institute (St Lucia)

URL:

http://www.qbi.uq.edu.au/neuroscience-seminars

Event category(s):

Full Description:: Dr Rosemary Bagot of the Icahn School of Medicine at Mt Sinai, Fishberg Department of Neuroscience, New York, USA

Title: Glutamatergic circuits in stress susceptibility: pathway specificity and transcriptional mechanisms

Abstract:

Evidence in both humans and animals points to dysregulated circuit function in depression, but the molecular mechanisms are unknown. Recent functional studies suggest that opposing alterations in prefrontal cortex (PFC) and ventral hippocampus (VHIP) neuronal activity regulate susceptibility to chronic social defeat stress (CSDS), a highly validated mouse model of depression (Bagot et al., 2015). To probe the molecular mechanisms mediating depression-associated functional alterations in these brain circuits we performed RNA-sequencing on multiple brain regions, from control animals and those susceptible or resilient to CSDS at multiple time points. Integrative network analysis identified distinct inter-regional co-regulation signatures and transcriptional networks regulating susceptibility and resilience in distinct brain regions with opposing regulation of susceptible-specific gene networks in PFC and VHIP. In vivo manipulations of multiple key regulators confirmed the functional significance of these networks at the level of gene transcription, synaptic regulation, and social interaction behavior, suggesting potential new targets for antidepressant drugs.