Parvalbumin interneuron activity in autism underlies susceptibility to PTSD-like memory formation
Alice Shaam Al Abed,
Tiarne Vickie Allen,
Noorya Yasmin Ahmed,
Azza Sellami,
Yovina Sontani,
Elise Caitlin Rawlinson,
Aline Marighetto,
Aline Desmedt,
Nathalie Dehorter
Affiliations
Alice Shaam Al Abed
Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia; The Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Corresponding author
Tiarne Vickie Allen
Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
Noorya Yasmin Ahmed
Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia; The Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia
Azza Sellami
Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U1215, INSERM, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France
Yovina Sontani
Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
Elise Caitlin Rawlinson
Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
Aline Marighetto
Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U1215, INSERM, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France
Aline Desmedt
Neurocentre Magendie, Physiopathologie de la plasticité neuronale, U1215, INSERM, F-33000 Bordeaux, France; Université de Bordeaux, F-33000 Bordeaux, France
Nathalie Dehorter
Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia; The Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Corresponding author
Summary: A rising concern in autism spectrum disorder (ASD) is the heightened sensitivity to trauma, the potential consequences of which have been overlooked, particularly upon the severity of the ASD traits. We first demonstrate a reciprocal relationship between ASD and post-traumatic stress disorder (PTSD) and reveal that exposure to a mildly stressful event induces PTSD-like memory in four mouse models of ASD. We also establish an unanticipated consequence of stress, as the formation of PTSD-like memory leads to the aggravation of core autistic traits. Such a susceptibility to developing PTSD-like memory in ASD stems from hyperactivation of the prefrontal cortex and altered fine-tuning of parvalbumin interneuron firing. Traumatic memory can be treated by recontextualization, reducing the deleterious effects on the core symptoms of ASD in the Cntnap2 KO mouse model. This study provides a neurobiological and psychological framework for future examination of the impact of PTSD-like memory in autism.
