Assistant Professor, Memorial University of Newfoundland
Associate Scientist, Centre for Addiction and Mental Health, Toronto
The involvement of the prefrontal cortex in affective disorders such as depression is very well established. Brain imaging and post-mortem studies have revealed abnormal activity and impaired homeostasis in prefrontocortical networks that regulate executive function and stress adaptation. However, we are only beginning to uncover the precise cortical neural systems crucial to underlying stress-related pathophysiologies and to complex psycho-affective symptoms. In our lab, we employ chronic stress paradigms (chronic mild stress, early parental deprivation, chronic cannabinoid exposure and prenatal immune activation) in the rodent to better understand the neurobiological underpinnings of depression and related disorders. A growing body of evidence highlights that discrete subtypes of GABAergic interneurons are selectively affected by chronic stress and are causally linked to abnormal behavioural phenotype. In particular, we find that depressive-like behaviour is linked to decreased activity of somatostatin-expressing interneurons, and this deficiency is associated with altered expression and function of activity-regulating neuronal elements, specifically the SK-type potassium channel, as well as other inhibitory receptors such as the cannabinoid CB1 receptor. These molecular mediators appear to be essential for synaptic homeostasis in the prefrontal cortex, and targeting them pharmacologically or through therapeutic brain stimulation may convey better antidepressant response, and could represent a promising novel approach for the development of more effective therapeutics.