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Parallel circuits from the bed nuclei of stria terminalis to the lateral hypothalamus drive opposing emotional states

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Giardino, William J., Eban-Rothschild, Ada, Christoffel, Daniel J., Li, Shi-Bin, Malenka, Robert C., de Lecea, Luis·2018·Nature Neuroscience
DOI 10.1038/s41593-018-0198-xPMC PMC6095688
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Abstract

Lateral hypothalamus (LH) neurons containing the neuropeptide hypocretin (HCRT; orexin) modulate affective components of arousal, but their relevant synaptic inputs remain poorly defined. Here we identified inputs onto LH neurons that originate from neuronal populations in the bed nuclei of stria terminalis (BNST; a heterogeneous region of extended amygdala). We characterized two non-overlapping LH-projecting GABAergic BNST subpopulations that express distinct neuropeptides (corticotropin-releasing factor, CRF, and cholecystokinin, CCK). To functionally interrogate BNST→LH circuitry, we used tools for monitoring and manipulating neural activity with cell-type-specific resolution in freely behaving mice. We found that Crf-BNST and Cck-BNST neurons respectively provide abundant and sparse inputs onto Hcrt-LH neurons, display discrete physiological responses to salient stimuli, drive opposite emotionally valenced behaviors, and receive different proportions of inputs from upstream networks. Together, our data provide an advanced model for how parallel BNST→LH pathways promote divergent emotional states via connectivity patterns of genetically defined, circuit-specific neuronal subpopulations.

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Authors
Giardino, W. J., Eban-Rothschild, A., Christoffel, D. J., Li, S.-B., Malenka, R. C., & de Lecea, L.
Affiliations
  • Stanford University (US)
  • University of Michigan (US)
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2018-07-23
Volume
21
Issue
8
Pages
1084-1095
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-018-0198-x
PMC
PMC6095688
OpenAlex
W2883542372
Cited by
252
References
7
Citations by year
2026: 24 · 2025: 31 · 2024: 30 · 2023: 39 · 2022: 29 · 2021: 37 · 2020: 36 · 2019: 20 · 2018: 6
FWCI
14.74
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Nature
  • National Institutes of Health
  • National Institute on Alcohol Abuse and Alcoholism (K99AA025677, F32AA022832)
  • National Institute of Mental Health (R01MH102638, F32MH106206, R01MH087592)
  • National Institute of Neurological Disorders and Stroke (P30NS069375)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
lateral hypothalamus, orexin, corticotropin-releasing factor, cholecystokinin, extended amygdala, emotional arousal, emotional valence, GABAergic neurons, neural circuits, parallel pathways, emotional behavior
MeSH terms
Orexins, Animals, Cholecystokinin, Conditioning, Operant, Emotions, gamma-Aminobutyric Acid, Hypothalamic Area, Lateral, Male, Mice, Inbred C57BL, Nerve Net, Neural Pathways, Neurons, Neuropeptides, Photic Stimulation, Self Stimulation, Septal Nuclei, Mice

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