Dopamine Release from the Locus Coeruleus Enables Temporal Binding in the Hippocampus
- 1University of California, Davis
Abstract
The hippocampus forms memories by associating events that are separated in time. These associations can be studied using trace conditioning, a procedure where a temporal gap is inserted between a conditional stimulus and an unconditional stimulus. Here, we examined how dopaminergic projections to CA1 support trace fear conditioning. Using fiber photometry and genetic lesions, we demonstrate that locus coeruleus (LC)-derived dopamine, rather than VTA input, is the primary source of dopamine in CA1 and is essential for trace learning. LC lesions reduced CA1 principal neuron activity and c-Fos expression. In-vivo imaging revealed that successful learning requires post-shock reactivation of stimulus-specific ensembles, a process compromised by LC lesions or long trace intervals. Finally, optogenetic stimulation of LC-CA1 projections during the post-shock period was sufficient to rescue learning in long-trace protocols. These findings identify LC-CA1 dopamine as a critical regulator of temporal binding via the facilitation of hippocampal memory trace reactivation.
Related
- Spatially confined dopamine from locus coeruleus axons selectively shapes hippocampal dynamics and action timing
- Stimulus-dependent dopamine dynamics from locus coeruleus axons
- Seizures in a Dravet Syndrome mouse model inhibit the locus coeruleus but locally evoke supraphysiologic norepinephrine release
- Nicotinic control of dopamine release shapes striatal output and engages adaptive action selection.
- Acute fentanyl induces opposing directions of changes in tonic and phasic dopamine release patterns and impairs Pavlovian task performance
BibTeX
@misc{crestani2026dopamine,
title = {{Dopamine Release from the Locus Coeruleus Enables Temporal Binding in the Hippocampus}},
author = {A. P. Crestani and C. R. A. F. Diniz and D. Carda and S. Maw and B. Wiltgen},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758657},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758657v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Dopamine Release from the Locus Coeruleus Enables Temporal Binding in the Hippocampus
AU - A. P. Crestani
AU - C. R. A. F. Diniz
AU - D. Carda
AU - S. Maw
AU - B. Wiltgen
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758657
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758657v1
AB - The hippocampus forms memories by associating events that are separated in time. These associations can be studied using trace conditioning, a procedure where a temporal gap is inserted between a conditional stimulus and an unconditional stimulus. Here, we examined how dopaminergic projections to CA1 support trace fear conditioning. Using fiber photometry and genetic lesions, we demonstrate that locus coeruleus (LC)-derived dopamine, rather than VTA input, is the primary source of dopamine in CA1 and is essential for trace learning. LC lesions reduced CA1 principal neuron activity and c-Fos expression. In-vivo imaging revealed that successful learning requires post-shock reactivation of stimulus-specific ensembles, a process compromised by LC lesions or long trace intervals. Finally, optogenetic stimulation of LC-CA1 projections during the post-shock period was sufficient to rescue learning in long-trace protocols. These findings identify LC-CA1 dopamine as a critical regulator of temporal binding via the facilitation of hippocampal memory trace reactivation.
ER -