PhD Graduate

PhD program:: XXXIV

Thesis title: Communication breakdown: investigation of brain networks alterations across time in a mouse model of traumatic stress

The stress response comprises a set of behavioral and physiological reactions, aimed at coping with the challenges encountered by the individual. However, traumatic events, which represent threats to the subject’s life, could alter the circuits involved in the reaction to stress, eventually leading to pathological conditions, such as post-traumatic stress disorder (PTSD). Although several structures are reported to suffer from functional and structural alterations following traumatic stress, the dynamics of the neural circuit involved are not completely understood. The predator exposure model of traumatic stress, which has proven to induce long-lasting anxiogenic effects in mice, was used to dissect traumatic stress-induced neural activity alterations of structures involved in stress response and reciprocally interconnected, namely prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC), dorsal and ventral hippocampus, basolateral amygdala (BLA) and the paraventricular nucleus of the thalamus (PVT). CD1 mice were placed in a safe enclosure to prevent direct attack and injuries and then subjected to a single 10-minutes exposure to a rat in a familiar context. Then, we assessed both acute and long-lasting anxiogenic effects of predator stress by elevated plus-maze (EPM). Using the immediate early gene Fos as a marker of neural activity, we evaluated neural activation after rat exposure and re-exposure to the stress context, 14 days following the traumatic stress. After predator exposure, Fos expression analysis showed hyperactivation of BLA and vCA1 in exposed mice compared to controls. Conversely, 14 days later, stressed mice showed reduced Fos expression in the PL cortex. To investigate whether BLA hyperactivation after rat exposure could account for mPFC hypoactivity at a later time point, resulting in more anxious behavior, we performed chemogenetic inhibition of BLA-mPFC projections right after the traumatic stress. However, the assessment of anxiety by EPM did not reveal any effect of the manipulation at an early time point. To explore how functional connections among structures of the circuit were altered by traumatic stress across time, we applied inter-regional correlation analysis and created network connectivity graphs. Analysis of topological properties of the network revealed that exposed mice showed a more integrated circuit at an early time point compared to controls. Conversely, 14 days after exposure, the stress network showed higher segregation than control, with structures of the circuit organized in clusters communicating by the PVT, which thus could play the role of the hub region of the circuit. The results presented in this study contribute to elucidating the dynamic of network alterations triggered by traumatic stress. Moreover, we show that, across time, the PVT plays a pivotal role in modulating the connectivity of the structures composing the network. This will provide an important key structure to manipulate the circuit in order to elucidate the causal involvement of specific projections in pathological reactions to stress and to investigate how stress-induced alterations of specific pathways may affect the network functionality. This may contribute to both the refinement of existing therapies and to the development of new therapeutic targets for stress-related disorder, such as the PTSD.

Research products

11573/1668215 - 2023 - Adult hippocampal neurogenesis and social behavioural deficits in the R451C Neuroligin3 mouse model of autism are reverted by the antidepressant Fluoxetine
Gioia, Roberta; Seri, Tommaso; Diamanti, Tamara; Fimmanò, Stefania; Vitale, Marina; Ahlenius, Henrik; Kokaia, Zaal; Tirone, Felice; Micheli, Laura; Biagioni, Stefano; Lupo, Giuseppe; Rinaldi, Arianna; De Jaco, Antonella; Cacci, Emanuele - 01a Articolo in rivista
paper: JOURNAL OF NEUROCHEMISTRY (Editore attuale:BLACKWELL PUBLISHING LTD, 9600 GARSINGTON RD, OXFORD, ENGLAND, OXON, OX4 2DG Lippincott, Williams & Wilkins:530 Walnut Street:Philadelphia, PA 19106:(800)638-3030, (301)223-2300, EMAIL:, INTERNET:, Fax: (301)223-2320, (301)223-2320) pp. - - issn: 0022-3042 - wos: WOS:000911198900001 (5) - scopus: 2-s2.0-85146133893 (7)

11573/1603150 - 2021 - Neural network alterations across time in a mouse model of traumatic stress
Seri, Tommaso; De Cicco, Greta; Mele, Andrea; Rinaldi, Arianna - 04f Poster
conference: 49th EBBS Meeting (Lausanne)
book: 49th EBBS Meeting - ()

11573/1496217 - 2020 - Time-dependent alterations in the medial prefrontal cortex after exposure to a traumatic stress in mice
Seri, Tommaso; De Cicco, Greta; Mele, Andrea; Rinaldi, Arianna - 04f Poster
conference: XII FENS Virtual Forum (Glasgow)
book: XII FENS Virtual Forum - ()

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma