A subiculum-hypothalamic pathway functions in dynamic threat detection and memory updating
Current Biology. 2024-05-01; :
DOI: 10.1016/j.cub.2024.05.006
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1. Curr Biol. 2024 May 17:S0960-9822(24)00604-3. doi: 10.1016/j.cub.2024.05.006.
Online ahead of print.
A subiculum-hypothalamic pathway functions in dynamic threat detection and
memory updating.
Viellard JMA(1), Melleu FF(2), Tamais AM(2), de Almeida AP(2), Zerbini C(2),
Ikebara JM(2), Domingues K(2), de Lima MAX(2), Oliveira FA(3), Motta SC(2),
Canteras NS(4).
Author information:
(1)Department of Anatomy, Institute of Biomedical Sciences, University of São
Paulo, São Paulo, SP 05508-000, Brazil; Institut des Maladies
Neurodégénératives, Université de Bordeaux, CNRS UMR 5293, Bordeaux, France.
(2)Department of Anatomy, Institute of Biomedical Sciences, University of São
Paulo, São Paulo, SP 05508-000, Brazil.
(3)Cellular and Molecular Neurobiology Laboratory (LaNeC)-Center for
Mathematics, Computing and Cognition (CMCC), Federal University of ABC, São
Bernardo do Campo, SP 09606-045, Brazil.
(4)Department of Anatomy, Institute of Biomedical Sciences, University of São
Paulo, São Paulo, SP 05508-000, Brazil. Electronic address: .
Animals need to detect threats, initiate defensive responses, and, in parallel,
remember where the threat occurred to avoid the possibility of re-encountering
it. By probing animals capable of detecting and avoiding a shock-related
threatening location, we were able to reveal a septo-hippocampal-hypothalamic
circuit that is also engaged in ethological threats, including predatory and
social threats. Photometry analysis focusing on the dorsal premammillary nucleus
(PMd), a critical interface of this circuit, showed that in freely tested
animals, the nucleus appears ideal to work as a threat detector to sense dynamic
changes under threatening conditions as the animal approaches and avoids the
threatening source. We also found that PMd chemogenetic silencing impaired
defensive responses by causing a failure of threat detection rather than a
direct influence on any behavioral responses and, at the same time, updated fear
memory to a low-threat condition. Optogenetic silencing of the main PMd targets,
namely the periaqueductal gray and anterior medial thalamus, showed that the
projection to the periaqueductal gray influences both defensive responses and,
to a lesser degree, contextual memory, whereas the projection to the anterior
medial thalamus has a stronger influence on memory processes. Our results are
important for understanding how animals deal with the threat imminence
continuum, revealing a circuit that is engaged in threat detection and that, at
the same time, serves to update the memory process to accommodate changes under
threatening conditions.
Copyright © 2024 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.cub.2024.05.006
PMID: 38810639
Conflict of interest statement: Declaration of interests The authors declare no
competing interests.