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Status |
Public on Apr 01, 2024 |
Title |
Amygdalostriatal transition zone neurons encode sustained valence to direct conditioned behaviors |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The amygdalostriatal transition zone (ASt) is anatomically poised to provide a shortcut between corticolimbic and basal ganglia circuitry, and mediate behavioral responses to stimuli in parallel with the amygdala. Like the amygdala, the ASt receives converging sensory input from thalamic and cortical pathways. However, the projections of the ASt are distinct from canonical outputs of the amygdala complex, and are integrated with striatal circuits involved in action selection. Despite this intriguing circuit connectivity, the function of the ASt is almost completely unknown. In the present study, we collected cellular resolution recordings of genetically-defined neurons during a valence discrimination task to interrogate the functional role of ASt circuitry, and characterized the transcriptomic profile of the ASt in comparison to neighboring regions. We find that ASt neurons, and specifically, ASt neurons expressing dopamine receptor 2 (D2+), robustly encode sustained conditioned responses to cues of negative valence. Selective inhibition of D2+ ASt neurons was found to cause a striking reduction in conditioned fear responses. We also used single-nucleus RNA sequencing to generate a comprehensive profile of gene expression in ASt neurons, and found that the ASt is genetically distinct from adjacent GABAergic brain regions. RNAscope labelling also confirmed there is a greater proportion of D2+ neurons than D1+ neurons in the ASt, a unique feature compared to other regions of the striatum. Together, our findings provide the first evidence the ASt is a critical structure for encoding learned associations to direct motivated behavior.
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Overall design |
Comparative single-cell gene expression profiling of pooled amygdalostriatal transition area, central amygdala, dorsal striatum, and tail of striatum samples using snRNA-seq
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Contributor(s) |
Mills F, Lee C, Howe J |
Citation missing |
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NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
DP1 AT009925 |
Neural Circuit Mechanisms of Social Homeostasis in Individuals and Supraorganismal Social Groups |
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES |
Kay Maxine Tye |
DP2 DK102256 |
A Novel Strategy for Combating Obesity: Reprogramming Neural Circuits |
MASSACHUSETTS INSTITUTE OF TECHNOLOGY |
Kay Maxine Tye |
R01 MH102441 |
Dissecting the Neural Circuits Encoding Positive and Negative Valence |
MASSACHUSETTS INSTITUTE OF TECHNOLOGY |
Kay Maxine Tye |
R01 MH115920 |
Exploring neural circuit mechanisms of social contact and social isolation |
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES |
Kay Maxine Tye |
K99 MH121563 |
Determining the role of amygdalostriatal transition zone circuits in associative learning and motivated behaviors |
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES |
Fergil Mills |
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Submission date |
Aug 17, 2022 |
Last update date |
Apr 01, 2024 |
Contact name |
Kay Tye |
E-mail(s) |
tye@salk.edu
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Organization name |
Salk Institute
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Department |
Systems Neurobiology Laboratory
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Lab |
Tye Lab
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Street address |
10010 N Torrey Pines Rd
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City |
La Jolla |
State/province |
CA |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (12)
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GSM6470102 |
Amygdalostriatal transition area biological replicate 1 |
GSM6470103 |
Amygdalostriatal transition area biological replicate 2 |
GSM6470104 |
Central amygdala biological replicate 1 |
GSM6470105 |
Central amygdala biological replicate 2 |
GSM6470106 |
Central amygdala biological replicate 3 |
GSM6470107 |
Dorsal striatum biological replicate 1 |
GSM6470108 |
Dorsal striatum biological replicate 2 |
GSM6470109 |
Dorsal striatum biological replicate 3 |
GSM6470110 |
Dorsal striatum biological replicate 4 |
GSM6470111 |
Tail of striatum biological replicate 1 |
GSM6470112 |
Tail of striatum biological replicate 2 |
GSM6470113 |
Tail of striatum biological replicate 3 |
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Relations |
BioProject |
PRJNA870402 |
Supplementary file |
Size |
Download |
File type/resource |
GSE211437_RAW.tar |
2.5 Gb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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