Partial or Complete Loss of Norepinephrine Differentially Alters Contextual Fear and Catecholamine Release Dynamics in Hippocampal CA1

by Leslie R. Wilson*, Nicholas W. Plummer*, Irina Y. Evsyukova, Daniela Patino, Casey L. Stewart, Kathleen G. Smith, Kathryn S. Konrad, Sydney A. Fry, Alex L. Deal, Victor W. Kilonzo, Sambit Panda, Natale R. Sciolino, Jesse D. Cushman, and Patricia Jensen
in Biological Psychiatry Global Open Science on January, 2024
*Equal Contribution


Background: Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning.

Methods: We generated 2 new mouse models of altered locus coeruleus–norepinephrine (NE) synthesis and utilized them together with GRABNE and GRABDA sensors and in vivo fiber photometry to investigate NE and dopamine (DA) release dynamics in the dorsal hippocampal CA1 during contextual fear conditioning.

Results: Aversive foot shock increased both NE and DA release in the dorsal CA1, while freezing behavior associated with recall of fear memory was accompanied by decreased release. Moreover, we found that freezing at the recent time point was sensitive to both partial and complete loss of locus coeruleus–NE synthesis throughout prenatal and postnatal development, similar to previous observations of mice with global loss of NE synthesis beginning postnatally. In contrast, freezing at the remote time point was compromised only by complete loss of locus coeruleus–NE synthesis beginning prenatally.

Conclusions: Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior and highlight complex relationships between genotype, sex, and NE signaling.


  title = {Partial or {{Complete Loss}} of {{Norepinephrine Differentially Alters Contextual Fear}} and {{Catecholamine Release Dynamics}} in {{Hippocampal CA1}}},
  author = {Wilson*, Leslie R. and Plummer*, Nicholas W. and Evsyukova, Irina Y. and Patino, Daniela and Stewart, Casey L. and Smith, Kathleen G. and Konrad, Kathryn S. and Fry, Sydney A. and Deal, Alex L. and Kilonzo, Victor W. and Panda, Sambit and Sciolino, Natale R. and Cushman, Jesse D. and Jensen, Patricia},
  year = {2024},
  month = jan,
  journal = {Biological Psychiatry Global Open Science},
  volume = {4},
  number = {1},
  pages = {51--60},
  issn = {2667-1743},
  doi = {10.1016/j.bpsgos.2023.10.001}