Neuronal populations mediating the effects of endocannabinoids on stress and emotionality

An adequate emotional response to stress is essential for survival and requires the fine-tuned regulation of several distinct neuronal circuits. Therefore, a precise control of these circuits is necessary to prevent behavioral imbalances. During the last decade, numerous investigations have evidenced that the endocannabinoid (eCB) system is able to crucially control stress coping. Its central component, the cannabinoid type 1 receptor (CB1 receptor), is located at the presynapse, where it is able to attenuate neurotransmitter release after its activation by postsynaptically produced and released eCBs. To date, the eCB system has been found to control the neurotransmitter release from several neuron populations (e.g. GABA, glutamate, catecholamines and monoamines), suggesting a general mechanism for tuning neuronal activity, and thereby regulating emotion and stress responses. In this review, we aim at summarizing the anatomical and functional relation of the eCB system to an adequate response to stressful situations. Of special interest will be neuronal connections to the hypothalamic-pituitary-adrenal axis, but also circuits between cortical structures, such as prefrontal cortex, amygdala and hippocampus, and subcortical regions, such as raphe nuclei and locus coeruleus. We further like to step toward allocating eCB system functions to distinct cellular subpopulations in the brain. It has emerged that the eCB system is spatially well defined, and its detailed knowledge is a prerequisite for understanding the eCB system in the context of controlling behavior. Thus, advanced approaches combining different genetic and pharmacological tools to dissect specific eCB system functions are of particular interest.