Changes at glutamate tripartite synapses in the prefrontal cortex of a new animal model of resilience/vulnerability to acute stress

Author:

Musazzi Laura1ORCID,Bonifacino Tiziana,Mingardi Jessica,Facchinetti RobertaORCID,Sala Nathalie,Frumento Giulia,Ndoj Elona,Valenza Marta,Paoli CaterinaORCID,Ieraci Alessandro,Torazza Carola,Balbi Matilde,Muhammad Nadeem,Guerinoni Michele,Russo Isabella,Milanese Marco,Scuderi Caterina2ORCID,Barbon Alessandro,Steardo Luca,Bonanno Giambattista,Popoli Maurizio3ORCID

Affiliation:

1. University of Milano-Bicocca

2. SAPIENZA University of Rome

3. University of Milan

Abstract

Abstract Stress represents a main risk factor for psychiatric disorders. Whereas it is known that even a single trauma may induce psychiatric disorders in humans, the mechanisms of vulnerability to acute stressors have been little investigated. In this study, we generated a new animal model of resilience/vulnerability to acute footshock (FS) stress in rats and analyzed early functional, molecular, and morphological determinants of stress vulnerability at tripartite glutamate synapses in the prefrontal cortex (PFC). We found that adult male rats subjected to FS can be deemed resilient (FS-R) or vulnerable (FS-V), based on their anhedonic phenotype 24 h after stress exposure, and that these two populations are phenotypically distinguishable up to two weeks afterwards. Basal presynaptic glutamate release was increased in the PFC of FS-V rats, while depolarization-evoked glutamate release and synapsin I phosphorylation at Ser9 were increased in both FS-R and FS-V. In FS-R and FS-V rats the synaptic expression of GluN2A and apical dendritic length of prelimbic PFC layers II–III pyramidal neurons were decreased, while BDNF expression was selectively reduced in FS-V. Depolarization-evoked (carrier-mediated) glutamate release from astroglia perisynaptic processes (gliosomes) was selectively increased in the PFC of FS-V rats, while GLT1 and xCt levels were higher and GS expression reduced in purified PFC gliosomes from FS-R. Overall, we show for the first time that the application of the sucrose intake test to rats exposed to acute FS led to the generation of a novel animal model of resilience/vulnerability to acute stress, which we used to identify early determinants of maladaptive response related to behavioral vulnerability to stress.

Publisher

Research Square Platform LLC

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