ALBERT

Description: Publication date: Available online 21 July 2016 Source: Cell Reports Author(s): Clémentine Bosch-Bouju, Thomas Larrieu, Louisa Linders, Olivier J. Manzoni, Sophie Layé Chronic social defeat stress (CSDS) is a clinically relevant model of mood disorders. The relationship between the CSDS model and a physiologically pertinent paradigm of synaptic plasticity is not known. Here, we found that cluster analysis of the emotional behavior states of mice exposed to CSDS allowed their segregation into anxious and non-anxious groups. Endocannabinoid-mediated spike-timing dependent plasticity (STDP) in the nucleus accumbens was attenuated in non-anxious mice and abolished in anxious mice. Anxiety-like behavior in stressed animals was specifically correlated with their ability to produce STDP. Pharmacological enhancement of 2-arachidonoyl glycerol (2-AG) signaling in the nucleus accumbens normalized the anxious phenotype and STDP in anxious mice. These data reveal that endocannabinoid modulation of synaptic efficacy in response to a naturalistic activity pattern is both a molecular correlate of behavioral adaptability and a crucial factor in the adaptive response to chronic stress. Graphical abstract Teaser Bosch-Bouju et al. used cluster analysis to segregate mice into anxious and non-anxious populations following social defeat. Endocannabinoid spike-timing-dependent plasticity is abolished in anxious mice only. Enhancement of endocannabinoid signaling in the nucleus accumbens restores anxiety-like behaviors and synaptic plasticity. Endocannabinoid plasticity is thus a synaptic marker of anxiety following social defeat.