ArticleMolecular psychiatry2022
A non-canonical GABAergic pathway to the VTA promotes unconditioned freezing.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- A Non-Mitophagy Activity of BNIP3L/NIX in Amygdala Glutamatergic Neurons is Essential for Contextual Fear Memory Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Stress induces oxytocin-Gαi-dependent remodeling of astrocytes to shape neuronal response in the amygdala.Nature communications · 2025Article
- Review
- Interpeduncular GABAergic neuron function controls threat processing and innate defensive adaptive learning.Molecular psychiatry · 2025Article
- Nicotine Withdrawal Drives Aversive Behaviors by Recruiting Inhibitory Interpeduncular Nucleus Inputs to the Laterodorsal Tegmentum in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The neural pathway from the superior subpart of the medial habenula to the interpeduncular nucleus suppresses anxiety.Molecular psychiatry · 2025Article
- Involvement of Matrix Metalloproteinases (MMP-2 and MMP-9), Inflammasome NLRP3, and Gamma-Aminobutyric Acid (GABA) Pathway in Cellular Mechanisms of Neuroinflammation in PTSD.International journal of molecular sciences · 2025Article
- Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Freezing 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.
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