| Autor: |
Franco LO; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.; PhD Program in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, Coimbra, Portugal., Carvalho MJ; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; MIT-Portugal Bioengineering Systems Doctoral Program, Coimbra, Portugal., Costa J; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; PhD Program in Experimental Biology and Biomedicine (PDBEB), University of Coimbra, Coimbra, Portugal., Ferreira PA; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal., Guedes JR; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal., Sousa R; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal., Edfawy M; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal., Seabra CM; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal., Cardoso AL; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal., Peça J; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. jpeca@cnc.uc.pt.; Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal. jpeca@cnc.uc.pt.; Department of Life Sciences, University of Coimbra, Coimbra, Portugal. jpeca@cnc.uc.pt. |
| Abstrakt: |
Social hierarchies are present in most mammalian species. In nature, hierarchies offer a tradeoff between reduction of in-group fighting between males, at the expense of an asymmetric sharing of resources. Early life experiences and stress are known to influence the rank an individual attains in adulthood, but the associated cellular and synaptic alterations are poorly understood. Using a maternal separation protocol, we show that care-deprived mice display a long-lasting submissive phenotype, increased social recognition, and enhanced explorative behavior. These alterations are consistent with an adaptation that favors exploration rather than confrontation within a group setting. At the neuronal level, these animals display dendritic atrophy and enhanced inhibitory synaptic inputs in medial prefrontal cortex (mPFC) neurons. To determine what could underlie this synaptic modification, we first assessed global gene expression changes via RNAseq, and next focused on a smaller subset of putatively altered synaptic receptors that could explain the changes in synaptic inhibition. Using different cohorts of maternally deprived mice, we validated a significant increase in the expression of Npy1r, a receptor known to play a role in maternal care, anxiety, foraging, and regulation of group behavior. Using electrophysiological recordings in adult mice while blocking NPY1R signaling, we determined that this receptor plays a key role in enhancing GABAergic currents in mice that experience maternal deprivation. Taken together, our work highlights the potential of regulating NPY1R in social anxiety disorders and the alterations induced in brain circuitry as a consequence of early life stress and adversity. |
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