Ayash Lab
Neural Basis of Resilience to Social Stress
Sie befinden sich hier:
Research
Our group focuses on understanding resilience and the mechanisms that differentiate individuals who recover from overwhelming stress from those who develop chronic illness. In particular, our research centers on the chronic social defeat (CSD) stress model in mice. Our studies have refined the CSD model, revealing that defeat-induced social avoidance behavior is shaped by conditioned learning. Specifically, we developed a social threat-safety test (STST), which demonstrated that some mice exhibit discrimination by avoiding only conspecifics from the aggressors' strain (discriminating-avoiders, DA), while others generalize their fear, avoiding even safe conspecifics (indiscriminate-avoiders, IA).
To further distinguish these behavioral phenotypes, we developed extinction training of social avoidance, which demonstrated that DAs alone exhibit extinction responsiveness when encountering aggressors from a safe distance, whereas IAs do not. This approach enhances the model's face validity by capturing discrimination and extinction—key features of resilience in humans. We substantiated our findings by identifying unique transcriptional signatures and brain connectivity between the groups.
Preliminary findings from our lab suggest that mesolimbic dopamine, particularly the ventral tegmental area (VTA) to nucleus accumbens (NAc) projection, plays a significant role in promoting discrimination and extinction within our model. Our research also shows that resilience can be fostered through a process termed stress inoculation, where mild stress exposure followed by adequate consolidation time appears to build resilience to future stressors in different contexts (social and physical), likely via an increase in NAc dopamine levels.
We hypothesize that dopamine within the NAc is critical for the learning and memory processes underlying resilience. Our future work aims to rigorously test this hypothesis across both sexes, with the ultimate goal of elucidating the neurobiological mechanisms that support resilience to stress.
Ayash S, Lingner T, Ramisch A, Ryu S, Kalisch R, Schmitt U, Müller MB. Fear circuit-based neurobehavioral signatures mirror resilience to chronic social stress in mouse. Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2205576120. doi: 10.1073/pnas.2205576120. Epub 2023 Apr 17. PMID: 37068238; PMCID: PMC10151471.
Ayash S, Schmitt U, Müller MB. Chronic social defeat-induced social avoidance as a proxy of stress resilience in mice involves conditioned learning. J Psychiatr Res. 2020 Jan;120:64-71. doi: 10.1016/j.jpsychires.2019.10.001. Epub 2019 Oct 9. PMID: 31634751.
Ayash S, Müller M, Schmitt U. Social Threat-Safety Test Uncovers Psychosocial Stress-Related Phenotypes. J Vis Exp. 2023 Dec 15;(202). doi: 10.3791/65640. PMID: 38163277.
Ayash S, Schmitt U, Lyons DM, Müller MB. Stress inoculation in mice induces global resilience. Transl Psychiatry. 2020 Jun 19;10(1):200. doi: 10.1038/s41398-020-00889-0. PMID: 32561821; PMCID: PMC7305209.
Lyons DM*, Ayash S*, Schatzberg AF, Müller MB. Ecological validity of social defeat stressors in mouse models of vulnerability and resilience. Neurosci Biobehav Rev. 2023 Feb;145:105032. doi: 10.1016/j.neubiorev.2023.105032. Epub 2023 Jan 4. PMID: 36608919.
Yuan R, Nechvatal JM, Buckmaster CL, Ayash S, Parker KJ, Schatzberg AF, Lyons DM, Menon V. Long-term effects of intermittent early life stress on primate prefrontal-subcortical functional connectivity. Neuropsychopharmacology. 2021 Jun;46(7):1348-1356. doi: 10.1038/s41386-021-00956-0. Epub 2021 Jan 25. PMID: 33495547; PMCID: PMC8134590.
Veer IM, Riepenhausen A, Zerban M, Wackerhagen C, Puhlmann LMC, Engen H, Köber G, Bögemann SA, Weermeijer J, Uściłko A, Mor N, Marciniak MA, Askelund AD, Al-Kamel A, Ayash S, Barsuola G, Bartkute-Norkuniene V, Battaglia S, Bobko Y, Bölte S, Cardone P, Chvojková E, Damnjanović K, De Calheiros Velozo J, de Thurah L, Deza-Araujo YI, Dimitrov A, Farkas K, Feller C, Gazea M, Gilan D, Gnjidić V, Hajduk M, Hiekkaranta AP, Hofgaard LS, Ilen L, Kasanova Z, Khanpour M, Lau BHP, Lenferink DB, Lindhardt TB, Magas DÁ, Mituniewicz J, Moreno-López L, Muzychka S, Ntafouli M, O'Leary A, Paparella I, Põldver N, Rintala A, Robak N, Rosická AM, Røysamb E, Sadeghi S, Schneider M, Siugzdaite R, Stantić M, Teixeira A, Todorovic A, Wan WWN, van Dick R, Lieb K, Kleim B, Hermans EJ, Kobylińska D, Hendler T, Binder H, Myin-Germeys I, van Leeuwen JMC, Tüscher O, Yuen KSL, Walter H, Kalisch R. Psycho-social factors associated with mental resilience in the Corona lockdown. Transl Psychiatry. 2021 Jan 21;11(1):67. doi: 10.1038/s41398-020-01150-4. PMID: 33479211; PMCID: PMC7817958.
Sarah Ayash | group leader | Einstein Independent Researcher | email
Haiyang Jing | PhD student | email
Alai Muheyati | PhD student | email
Dejiao Xu | PhD student | email
Contact
Sarah Ayash
Charité-Universitätsmedizin Berlin
Neuroscience Research Center / Charité CrossOver
Email: sarah.ayash(at)charite.de