Dorsal midline thalamus to CeA circuit reorganization by high potency cannabinoids

Project: Research project

Project Details


The prevalence of Cannabis consumption has steadily and consistently increased in the past few years, both for recreational and medicinal use. In addition to its therapeutic effects, cannabis, especially high potency cannabinoids, have been found to cause adverse mental health outcomes, like anxiety disorders and psychotic episodes. However, little is known about the underlying mechanisms contributing to these adverse effects. We aim to test the hypothesis that high potency cannabinoid induced plasticity in afferent input strength from dorsal midline thalamus (dMT) to defined neuronal populations in the Central Amygdala (CeA) contributes to some of these pathophysiological consequences. We will utilize a combination of viral and genetic tools, along with ex vivo optogenetics to address 1) whether cannabinoid receptor agonist CP 55,940 increases synaptically driven firing in CeA SOM cells and 2) assess how fear learning alters dMT to CeA pathway, along with local circuit inhibition landscape and 3) study the effects of deleting CB1R from selective terminals on fear learning. Our preliminary data indicate that relative strength of excitatory input from dMT to CeA is biased towards SOM+ cells (in comparison to CRF+ and putative PKCd+ cells) and that CP 55,940 tilts this balance further towards even higher excitatory drive by disinhibiting this neuronal population. As SOM+ cells are the primary regulator of fear output in the CeA, overdrive in SOM excitability would lead to pathological fear states. These investigations would elucidate distinct synaptic mechanisms by which cannabinoids reorganize circuits that lead to pathological behavioral manifestations of Cannabis over use.
Effective start/end date1/15/231/14/25


  • Brain & Behavior Research Foundation (30966)


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