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Reaching circuitry level of understanding of the comorbidity of chronic pain and mood disorders

Uncontrolled and persistent pain strongly associates with anxiety and depressive disorders, and is among the most common cause of disability impairing the quality of life. Over the last 10 years, our group has established and validated paradigms designed to model this comorbidity in the mouse.

 Uncontrolled and persistent pain strongly associates with anxiety and depressive disorders, and is among the most common cause of disability impairing the quality of life. Over the last 10 years, our group has established and validated paradigms designed to model this comorbidity in the mouse. We then exploited this model to uncover individual brain structures and molecular mechanisms affected by chronic pain. Among candidates, the anterior cingulate cortex (ACC), a structure common to the default mode, salience and reward networks, appears critical in pain and emotional processing. Our rodent studies further supported the implication of the ACC in mood control. Indeed, in naive mice, a short-term optogenetic activation of glutamatergic pyramidal neurons was sufficient to trigger anxiodepressive-like behaviours. Secondly, in a neuropathic pain model, our in vivo electrophysiological single unit recordings highlighted changes in ACC neuronal activity, with a long-lasting increase in spontaneous firing and bursting activity during pain-induced depressive-like behaviours.


 


 To go further, we now aim at reaching a network-level of understanding of these issues. Our resting state functional magnetic resonance imaging results clearly showed modifications in the circuitry of the Basolateral amygdala (BLA)-ACC in our rodent model of comorbid chronic pain and depression. By using optogenetic approach, we further showed that the optogenetic activation of the BLA-ACC pathway induced depressive-like behaviours in naive mice. Importantly, inhibiting this pathway was sufficient to block neuropathic pain-induced depressive-like behaviours. Altogether these data reveal the importance of BLA-ACC pathway in emotional dysregulation and highlight the need of dissecting circuits rather than single structure to deepen our understanding of the mechanisms underlying mood disorders.


 


More about the speaker and her research


Ypec Yalcin


Webseite:
https://www.bcf.uni-freiburg.de/events/bernstein-seminar/2021/20210413_Yalcin

Interne Verantwortlichkeit:
Bernstein Center Freiburg (BCF)

Kontakt:
Fiona Siegfried
0761 203 9549
siegfried@bcf.uni-freiburg.de