Effects of acute and chronic restraint stress during adolescence on endocannabinoid-mediated synaptic plasticity in the mouse hippocampal dentate gyrus

Abstract

Our society lives embedded in stress. This causes numerous environmental factors that precipitate and exacerbate psychiatric disorders, such as anxiety and depression. In all organisms, stress is recognized as an adaptive response and is essential for survival to re-establish homeostasis. The brain is the most sensitive organ to stress and responsible for generating an adaptation to stressors, both social and physical. In mammals, multiple brain areas, such as the hippocampus, amygdala, prefrontal cortex and hypothalamus are activated in response to the threat of homeostasis disruption. In particular, the hippocampus is critically involved in many forms of learning and memory, as well as emotional processing and stress. Despite adolescence being a vital stage where numerous changes occur, research on changes in stress-related synaptic plasticity and the brain has been focused more on childhood and adulthood. The endocannabinoid (eCB) system is widely distributed in the central nervous system and participates in many brain functions. To better understand the role of the eCB system in the context of anxiety and how to cope stress is necessary an integrated view of the endocannabinoid-mediated control in brain regions involved in stress processing and regulation. In this Doctoral Thesis, adolescent Swiss male mice were used to investigate the localization and function of the CB1 receptor at the excitatory medial perforant path (MPP) synapses in the dentate molecular layer of the hippocampus in control, acute and chronic restraint stress condition. The rational behind is that these synapses show high efficiency in neuronal activation and contribute to the excitatory tri-synaptic circuit related to learning and memory in the hippocampus. Furthermore, restraint stress damages the entorhinal cortex and dentate gyrus affecting the entorhino-dentate (perforant) pathway. We studied in the Thesis the effect of acute and chronic restraint stress to adolescent mice on synaptic transmission and in particular on CB1 receptor dependent long-term depression at the excitatory MPP-granule cell synapses.