B04 will investigate the role of anandamide signaling in resilience. Anandamide is an endocannabinoid and ligand of the cannabinoid CB1 receptor, implicated in fear extinction, relief from anxiety and HPA axis down-regulation. It is expected that anandamide signaling at the time of stressor exposure facilitates stress response regulation by its effects on neuronal excitability as well as large-scale network function. B04 will genetically enhance anandamide signaling at precise time points during stressor exposure in selected neurons of the network and investigate its effect on excitability, network function, and resilience.
Hedrich J, Angamo EA, Conrad A, Lutz B, Luhmann HJ (2020) Cell type specific impact of cannabinoid receptor signaling in somatosensory barrel map formation in mice. J Comp Neurol 528(1):3-13 doi:10.1002/cne.24733
Kirkedal C, Elfving B, Müller HK, Moreira FA, Bindila L, Lutz B, Wegener G, Liebenberg N (2019) Hemisphere-dependent endocannabinoid system activity in prefrontal cortex and hippocampus of the Flinders Sensitive Line rodent model of depression. Neurochem Int 125:7-15. doi: 10.1016/j.neuint.2019.01.023.
Zimmermann T, Bartsch JC, Beer A, Lomazzo E, Guggenhuber S, Lange MD, Bindila L, Pape HC, Lutz B (2019) Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses. Neuropsychopharmacology 44(8):1377–1388 doi: 10.1038/s41386-018-0274-7.
Kalisch R, Baker DG, Basten U, Boks MP, Bonanno GA, Brummelman E, Chmitorz A, Fernàndez G, Fiebach CJ, Galatzer-Levy I, Geuze E, Groppa S, Helmreich I, Hendler T, Hermans EJ, Jovanovic T, Kubiak T, Lieb K, Lutz B, Müller MB, Murray RJ, Nievergelt CM, Reif A, Roelofs K, Rutten BPF, Sander D, Schick A, Tüscher O, Van Diest I, van Harmelen A-L, Veer IM, Vermetten E, Vinkers CH, Wager TD, Walter H, Wessa M, Wibral M, Kleim B (2017) The resilience framework as a strategy to combat stress-related disorders. Nat Hum Behav 1:784-90.