In SFB 1280, all subprojects base their studies on a shared set of preassumptions on extinction learning
On this site, find the seven overarching hypotheses briefly sketched.
On the linked following, the hypotheses are explained in more detail. >>
Extinction learning includes both forgetting of the original association as well as a new learning of inhibition: this controversial assumption will be investigated in the SFB 1280 both using single cell recordings in animals, intracranial recordings in humans as well as and by conducting behavioral studies. During single cell recordings in animals with parallel optogenetic manipulation we expect (possibly in different brain regions) in the same experimental phase, some neurons stop responding to the conditioned, while other cell types may start to respond to the absence of the unconditioned stimulus. >>
Extinction learning of aversive and appetitive associations are manifested similarly in behaviour, but are partially distinct on a neurobiological level: Appetitive and aversive extinction procedures differ less at the behavioral level but still can vary substantially at the neural level: extinction learning is effectively investigated with the fear conditioning paradigm (such as in the SFB-TRR 58). However, extinction learning is not only a domain of aversive associations, but works similarly with appetitive stimuli. This could mislead to the assumption that the neurobiological mechanisms of extinction learning are identical for aversive and appetitive associations. Probably, this is not the case. For example, the endocannabinoid system primarily plays a role in the extinction learning for aversive, but not appetitive associations. Also the dopaminergic system and parts of projections to amygdala neurons show clear differences between the processing of aversive and appetitive stimuli and conditionings. Especially for therapy of drug addiction a greater detailed knowledge of neurobiological mechanisms of the extinction of appetitive stimuli is urgently required. >>
The neural extinction network is considerably larger than the triad of amygdala, hippocampus and prefrontal cortex: already in hypothesis 4 we argued that probably wide parts of the corticostriatal system are involved in extinction. Another important structure is the cerebellum, which is probably involved in both learning of context as well as extinction of the conditioned response. It has long been known that the cerebellum is also the place where learned associations are stored. Its role in extinction, especially of conditioned fear, has however not yet been well studied. There are some pieces of evidence indicating that the cerebellar cortex is especially important for the deletion of associations. In the SFB 1280 these considerations will be investigated using high resolution imaging techniques with healthy controls and patients with diseases affecting the cerebellum, as well as non-invasive brain stimultion paradigms. Additionally, the SFB focus group “Neuroimaging” will analyze cerebellar activation patterns for different extinction studies across imaging projects. >>
Context stimuli are only weakly associated with the unconditioned stimulus and control behaviour through the interaction of the prefrontal cortex and the hippocampus: Context stimuli are only weakly associated with the unconditioned stimulus and control behavior through the interaction between the prefrontal cortex and the hippocampus: it is often assumed that context stimuli (e.g. traffic) are of a different sort in comparison to conditioned stimuli (e.g. screeching tyres before an accident). We think this is wrong and assume that the differences between these stimuli categories are manifested in the strength of association and temporal structure. Because of the latter the hippocampus is primarily involved in our hypothesis. To support this, it is planned to employ single cell recordings in animals with optogenetic manipulation during extinction processes, also taylored behavioral experiments in humans and theoretical and neuroscientific investigations in learning robots. >>
Neuroendocrine and immunological processes are part of the extinction process: it is known that different transmitter systems such as dopamine, noradrenaline and serotonin play an important role in extinction learning. Therefore, these transmitter systems are part of this SFB, in which especially the serotonergic system will be investigated using complex optogenetic methods. One focus of the SFB 1280 is the investigation of the stress induced activation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system. These systems have differential effects on consolidation and retrieval of memory and will be explored further in several behavioral as well as neuroimaging experiments. Additionally, the immune system is subject to conditioning and thereby an essential component of learning processes, that form the basis for extinction learning. This aspect will also be tested in humans and animals. >>
Structure specific brain maturation as well as individual variability in extinction learning create different conditioning and pathological patterns: The amygdala develops faster than the hippocampus. This could contribute to the fact that extinction in very young children primarily consists of deletion of old associations, later complemented with learned inhibition. Also, the investigation of interindividual variability in conditioning can possibly predict differences in the extinction process, e.g. in pain conditioning. Several groups within the SFB which are specialized in developmental psychological, neurological and clinical therapeutic approaches, will test this hypothesis. Additionally, in one project exposure therapy will be performed in a scanner to find neural correlates of extinction learning during behavioral therapy. >>
Hadamitzky, M., Engler, H., and Schedlowski, M. (2013). Learned immunosuppression: extinction, renewal, and the challenge of reconsolidation. J. Neuroimmune Pharm. 8: 180–188.
Marsicano, G., Wotjak, C.T., Azad, S.C., Bisogno, T., Rammes, G., Cascio, M.G., Hermann, H., Tang, J., Hofmann, C., Zieglgänsberger, W., Di Marzo, V., and Lutz, B. (2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature, 418: 530–534.
Medina, J.F., Nores, W.L., and Mauk, M.D. (2002). Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses. Nature, 416: 330–333.
Swanson, L.W. and Petrovich, G.D. (1998). What is the amygdala? Trends Neurosci. 21: 323–331.
Wolf, O.T. (2017). Stress and Memory Retrieval: Mechanisms and Consequences. Curr. Opin. Behav. Sci. 14: 40–46.