Optogenetics has proven to be a highly useful tool to delineate the function of distinct proteins. Here, this approach was combined with fMRI to activate in-vivo selectively two interacting, but supposedly opposing, neuronal circuits of the central lateral amygdala (CEl). A classical fMRI paradigm was chosen to study the influence of the activation of either PKCδ- or somatostatin-expressing neurons on central pain processing, and to identify involved brain networks or areas. PKCδ was found to act preferentially anti-nociceptive by controlling via thalamus higher-order brain regions. Somatostatin on the other hand was shown to interact very closely with brainstem regions, controlling in a “bottom-up”-fashion thalamus, limbic system and cortex.