Ron Stoop Lab    

3. Comparing the circuits in animals and human subjects with specific lesions in the amygdala (collab. Sout-Africa)

Recently, selective bilateral BLA damage was shown in a group of subjects from the Northern Cape of South Africa, caused by a rare, i.e. faulty, mutation of the ECM1 gene (Urbach-Wiethe disease; UWD). Using neuroimaging techniques it was also shown that in these UWD subjects the CMA remains intact and functional. Data of the group of Prof. Jack van Honk at UCT correspond to animal models in showing that innate as well as social fear in these UWD subjects has shifted from instrumental behaviors (sub-served by the BLA) to impulsive mechanisms (sub-served by CMA). Furthermore, recent high-resolution fMRI studies using acute hormone administration in humans (testosterone and oxytocin) have indicated that the effects of these hormones are also mediated by amygdala sub regions. Indeed, these findings also agree with recent rodent research from our group Within this collaboraiton we will use a selection of paradigms measuring fear learning, fear responses to distant and nearby threat, and social fear. These will be used with neuroimaging and measurements of the physiological expression of fear in human subjects with selective BLA damage and healthy controls (at UCT), and compared to data from a project wherein similar paradigms are used in rodents (at UniL). ECM1 knock out, pharmacological and optogenetic methods for selective inactivation of neuron populations will be applied to influence amygdala sub regions (BLA and CMA) in rodents, to study the corresponding effects on the behavioral (e.g. freezing vs. fight/flight) and physiological expression of fear (parasympathetic vs. sympathetic activation). Furthermore, in both humans and rodents we will apply placebo-controlled acute hormone administration (oxytocin and testosterone) to investigate and compare effects on these same fear behaviors and the underlying brain functions. With these approaches we aim to construct a translational amygdala-centered neurobehavioral model of fear.

Funded by the South-African Swiss resarch program

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Tafelberg (Südafrika) (Südafrika)

University of Cape Town (UCT), located in the province of Wester Cape, (South-West of South-Africa) is the oldest university in South Africa and highest ranking in Africa.