A non-canonical GABAergic pathway to the VTA promotes unconditioned freezing

Author:

Broussot Loïc,Contesse Thomas,Costa-Campos Renan,Glangetas Christelle,Royon Léa,Fofo Hugo,Lorivel ThomasORCID,Georges FrançoisORCID,Fernandez Sebastian P.ORCID,Barik JacquesORCID

Abstract

AbstractFreezing is a conserved defensive behaviour that constitutes a major stress-coping mechanism. Decades of research have demonstrated a role of the amygdala, periaqueductal grey and hypothalamus as core actuators of the control of fear responses, including freezing. However, the role that other modulatory sites provide to this hardwired scaffold is not known. Here, we show that freezing elicited by exposure to electrical foot shocks activates laterodorsal tegmentum (LDTg) GABAergic neurons projecting to the VTA, without altering the excitability of cholinergic and glutamatergic LDTg neurons. Selective chemogenetic silencing of this inhibitory projection, but not other LDTg neuronal subtypes, dampens freezing responses but does not prevent the formation of conditioned fear memories. Conversely, optogenetic-activation of LDTg GABA terminals within the VTA drives freezing responses and elicits bradycardia, a common hallmark of freezing. Notably, this aversive information is subsequently conveyed from the VTA to the amygdala via a discrete GABAergic pathway. Hence, we unveiled a circuit mechanism linking LDTg-VTA-amygdala regions, which holds potential translational relevance for pathological freezing states such as post-traumatic stress disorders, panic attacks and social phobias.

Funder

Fondation pour la Recherche Médicale

Publisher

Springer Science and Business Media LLC

Subject

Cellular and Molecular Neuroscience,Psychiatry and Mental health,Molecular Biology

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