PhD Scientific Days 2023

Neurosciences - Posters H

Afferents of the Paraventricular Thalamic Nucleus (PVT) and the Role of PVT in Stress Induced Behavioral Changes

Text of the abstract

Introduction
Traumatic events can lead to the emergence of acute stress disorder (ASD), which is characterized by avoidance, hyperarousal, negative mood, and occurs in the initial month after the traumatic event. The calretinin expressing neurons in the paraventricular nucleus of the thalamus (PVT/CR+) form a critical hub between brainstem and forebrain areas and play essential roles in arousal, anxiety and stress regulating circuit operations.
Aims
In this study we tested whether the post-stress activity of PVT/CR+ neurons, following exposure to a natural stressor (fox odor, 2MT), contributes to the emergence of ASD like phenotype.
Method
We examined how post-stress optogenic inhibition (SwiChR) of the PVT/CR+ neurons affects locomotion, nesting behavior, stress hormone levels and c-Fos activity at the projection areas of PVT/CR+ neurons. We also investigated, which areas send GABAergic and glutamatergic inputs to PVT/CR+ cells and to what extent do these inputs converge or segregate in the PVT. We used retrograde and anterograde virus labeling in vGLUT2-Cre, VGAT-Cre and VGLUT2-Cre/vGAT-Flp double transgenic mouse lines and analyzed the PVT projecting cells and their fibers in the PVT by fluorescence and confocal microscopy after immunohistochemical staining.
Results
We found that post-stress photoinhibition (1 hour) of PVT/CR+ cells prevented the acute stress induced changes including increased locomotor activity, disturbed nesting behavior, elevated corticosterone levels and increased c-Fos expression in the PVT/CR+ neurons and their projection areas. We also found that the origins of GABAergic and glutamatergic subcortical inputs to PVT largely segregate. Afferents from these subcortical centers selectively innervated PVT/CR+ cells and overlapped significantly in PVT. In contrast, cortical inputs segregated from subcortical inputs and they innervated the peripheral part of the nucleus.
Conclusion
Collectively, our findings indicate that PVT/CR+ neurons integrate excitatory and inhibitory information from numerous structures related to stress and salience, and the post-stress activity of PVT/CR+ neurons is critical in the emergence of ASD-like phenotype. We found, that post-stress inhibition of PVT/CR+ neurons is sufficient to prevent these changes.
Funding
Supported by European Research Council – FRONTHAL – 742595