Kurzfassung

The project aims at identifying the critical brain regions and synaptic networks underlying the fear-alleviating effects of the endocannabinoid system via cannabinoid type (CB1) receptor activation. The mechanisms will be tackled on a molecular biological, electrophysiological and behavioral level. In a first step, mutants with CB1 receptor deficiencies in distinct brain regions and/or neuronal subpopulations will be generated using the Cre/loxP technique in combination with Cre...The project aims at identifying the critical brain regions and synaptic networks underlying the fear-alleviating effects of the endocannabinoid system via cannabinoid type (CB1) receptor activation. The mechanisms will be tackled on a molecular biological, electrophysiological and behavioral level. In a first step, mutants with CB1 receptor deficiencies in distinct brain regions and/or neuronal subpopulations will be generated using the Cre/loxP technique in combination with Cre recombinase-expressing transgenes or stereotactic injections of adeno-associated virus expressing Cre recombinase, respectively. In a second step, a novel mutation of the CB1 receptor gene will be generated that enables the conditional re-expression of CB1 receptors in specific neurons/region on a CB1 receptor deficient state. Behavioral phenotypes with regard to fear memory and extinction will be determined, and in vivo multiple site recordings will be used to assess the electrophysiological correlates in amygdala, prefrontal cortex and hippocampus in freely behaving animals. By combining the expertise of the two applicants, we thus aim at identifying the sites and functional impact of CB1 receptor expression that are both necessary and sufficient for fear memory extinction. We assume this project to reveal the mechanisms and functional impact of CB1 receptor signalling in defined populations of neurons for fear memory, in particular when it comes to extinction.» weiterlesen» einklappen