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Peer-reviewedCC BYNeuron

Amygdalostriatal transition zone neurons encode sustained cue responses to guide defensive behaviors

  • Fergil Mills1
  • Christopher R. Lee2
  • James R. Howe3
  • Hao Li4
  • Maria N. Keisler5
  • Shan Shao6
  • Felix Taschbach7
  • Mackenzie Lemieux4
  • Faith Aloboudi8
  • Jesse White8
  • May G. Chan8
  • Matilde Borio4
20 more authors
  • Laurel R. Keyes8
  • Hannah S. Chen9
  • Fabiha Bushra10
  • Gates P. Schneider8
  • Dani P. Lemmon10
  • Kyung J. Lee10
  • Alexa L. Gross11
  • Kanha Batra7
  • Reesha R. Patel4
  • Meenakshi M. Asokan4
  • Jeremy Delahanty8
  • Christian Cazares4
  • Christopher R Heyman10
  • Nicholas B Poll10
  • Liezl Maree4
  • Romy Wichmann8
  • Talmo Pereira4
  • Marcus K. Benna3
  • Cory M. Root3
  • Kay M. Tye12
12 affiliations
  1. 1Salk Institute for Biological Studies, La Jolla, CA, USA; University of Utah, Salt Lake City, UT, USA. Electronic address: [email protected]
  2. 2Salk Institute for Biological Studies, La Jolla, CA, USA; University of California, San Diego, La Jolla, CA, USA; Howard Hughes Medical Institute, La Jolla, CA, USA
  3. 3University of California, San Diego, La Jolla, CA, USA
  4. 4Salk Institute for Biological Studies, La Jolla, CA, USA
  5. 5University of California, San Diego, La Jolla, CA, USA; Howard Hughes Medical Institute, La Jolla, CA, USA
  6. 6Peking University, Beijing, China
  7. 7Salk Institute for Biological Studies, La Jolla, CA, USA; University of California, San Diego, La Jolla, CA, USA
  8. 8Salk Institute for Biological Studies, La Jolla, CA, USA; Howard Hughes Medical Institute, La Jolla, CA, USA
  9. 9Massachusetts Institute of Technology, Cambridge, MA, USA
  10. 10University of Utah, Salt Lake City, UT, USA
  11. 11Wellesley College, Wellesley, MA, USA
  12. 12Salk Institute for Biological Studies, La Jolla, CA, USA; University of California, San Diego, La Jolla, CA, USA; Howard Hughes Medical Institute, La Jolla, CA, USA; Kavli Institute for the Brain and Mind, La Jolla, CA, USA. Electronic address: [email protected]
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Abstract

Here, we present the amygdalostriatal transition zone (ASt) as a missing piece of a highly conserved process of paramount importance for survival, which represents an internal state (e.g. fear) that can be expressed in multiple motor outputs (e.g. freezing or escape). From in vivo cellular resolution recordings that include both electrophysiology and calcium imaging, we find that ASt neurons are sparse coding, extremely high signal-to-noise, and maintain a sustained response for negative valence stimuli for the duration of the defensive behavior. Photostimulation of the ASt is sufficient to drive freezing and avoidance behaviors. Using single-nucleus RNA sequencing and in situ RNA labelling we find the ASt is genetically distinct from adjacent striatal and amygdalar structures. Using in vivo calcium imaging, we find that the Drd2+ population encodes negative valence, and find that optogenetic inhibition of Drd2+ ASt neurons reduces cue-conditioned fear responses. Funding Information: K.M.T. is an HHMI Investigator and the Wylie Vale chair at the Salk Institute for Biological Studies and this work was supported by funding from the JPB Foundation, the PIIF, PNDRF, JFDP, New York Stem Cell Foundation, Klingenstein Foundation, McKnight Foundation, The Salk Institute, Howard Hughes Medical Institute, Clayton Foundation, Kavli Foundation, Dolby Family Fund, R01-MH115920 (NIMH), R37-MH102441 (NIMH), the NIH Director’s New Innovator Award DP2- DK102256 (NIDDK) and Pioneer Award DP1-AT009925 (NCCIH). F.M. was supported by a CIHR Postdoctoral Fellowship and a K99/R00 NIH Pathways to Independence Award (K99 MH121563). H.L. was supported by a K99/R00 NIH Pathways to Independence Award (K99 DA055111-01). R.R.P. was supported by a K99/R00 NIH Pathways to Independence Award (K99 AA029180). S.S. was supported by China Scholarship Council grant 201806010370. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All experimental procedures were carried out in accordance with NIH guidelines and approval of the Salk Institutional Animal Care and Use Committee.

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Cite

BibTeXRIS
BibTeX
@article{mills2026amygdalostriatal,
  title = {{Amygdalostriatal transition zone neurons encode sustained cue responses to guide defensive behaviors}},
  author = {Fergil Mills and Christopher R. Lee and James R. Howe and Hao Li and Maria N. Keisler and Shan Shao and Felix Taschbach and Mackenzie Lemieux and Faith Aloboudi and Jesse White and May G. Chan and Matilde Borio and Laurel R. Keyes and Hannah S. Chen and Fabiha Bushra and Gates P. Schneider and Dani P. Lemmon and Kyung J. Lee and Alexa L. Gross and Kanha Batra and Reesha R. Patel and Meenakshi M. Asokan and Jeremy Delahanty and Christian Cazares and Christopher R Heyman and Nicholas B Poll and Liezl Maree and Romy Wichmann and Talmo Pereira and Marcus K. Benna and Cory M. Root and Kay M. Tye},
  journal = {Neuron},
  year = {2026},
  month = sep,
  doi = {10.1016/j.neuron.2026.08.012},
  url = {https://doi.org/10.1016/j.neuron.2026.08.012},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Amygdalostriatal transition zone neurons encode sustained cue responses to guide defensive behaviors
AU  - Fergil Mills
AU  - Christopher R. Lee
AU  - James R. Howe
AU  - Hao Li
AU  - Maria N. Keisler
AU  - Shan Shao
AU  - Felix Taschbach
AU  - Mackenzie Lemieux
AU  - Faith Aloboudi
AU  - Jesse White
AU  - May G. Chan
AU  - Matilde Borio
AU  - Laurel R. Keyes
AU  - Hannah S. Chen
AU  - Fabiha Bushra
AU  - Gates P. Schneider
AU  - Dani P. Lemmon
AU  - Kyung J. Lee
AU  - Alexa L. Gross
AU  - Kanha Batra
AU  - Reesha R. Patel
AU  - Meenakshi M. Asokan
AU  - Jeremy Delahanty
AU  - Christian Cazares
AU  - Christopher R Heyman
AU  - Nicholas B Poll
AU  - Liezl Maree
AU  - Romy Wichmann
AU  - Talmo Pereira
AU  - Marcus K. Benna
AU  - Cory M. Root
AU  - Kay M. Tye
PY  - 2026
DA  - 2026/09/01
JO  - Neuron
DO  - 10.1016/j.neuron.2026.08.012
UR  - https://doi.org/10.1016/j.neuron.2026.08.012
AB  - Here, we present the amygdalostriatal transition zone (ASt) as a missing piece of a highly conserved process of paramount importance for survival, which represents an internal state (e.g. fear) that can be expressed in multiple motor outputs (e.g. freezing or escape). From in vivo cellular resolution recordings that include both electrophysiology and calcium imaging, we find that ASt neurons are sparse coding, extremely high signal-to-noise, and maintain a sustained response for negative valence stimuli for the duration of the defensive behavior. Photostimulation of the ASt is sufficient to drive freezing and avoidance behaviors. Using single-nucleus RNA sequencing and in situ RNA labelling we find the ASt is genetically distinct from adjacent striatal and amygdalar structures. Using in vivo calcium imaging, we find that the Drd2+ population encodes negative valence, and find that optogenetic inhibition of Drd2+ ASt neurons reduces cue-conditioned fear responses. Funding Information: K.M.T. is an HHMI Investigator and the Wylie Vale chair at the Salk Institute for Biological Studies and this work was supported by funding from the JPB Foundation, the PIIF, PNDRF, JFDP, New York Stem Cell Foundation, Klingenstein Foundation, McKnight Foundation, The Salk Institute, Howard Hughes Medical Institute, Clayton Foundation, Kavli Foundation, Dolby Family Fund, R01-MH115920 (NIMH), R37-MH102441 (NIMH), the NIH Director’s New Innovator Award DP2- DK102256 (NIDDK) and Pioneer Award DP1-AT009925 (NCCIH). F.M. was supported by a CIHR Postdoctoral Fellowship and a K99/R00 NIH Pathways to Independence Award (K99 MH121563). H.L. was supported by a K99/R00 NIH Pathways to Independence Award (K99 DA055111-01). R.R.P. was supported by a K99/R00 NIH Pathways to Independence Award (K99 AA029180). S.S. was supported by China Scholarship Council grant 201806010370. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All experimental procedures were carried out in accordance with NIH guidelines and approval of the Salk Institutional Animal Care and Use Committee.
SN  - 0896-6273
SN  - 1097-4199
ER  -