The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats
Open accessAbstract
Summary Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing.
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Cites
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444
Ultrasensitive fluorescent proteins for imaging neuronal activity
Chen, T.-W., Wardill, T. J., Sun, Y., Pulver, S. R., Renninger, S. L., Baohan, A., Schreiter, E. R., Kerr, R. A., Orger, M. B., Jayaraman, V., et al. (2013) · Nature · doi:10.1038/nature12354 · Cited by 6,474
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572
A mesoscale connectome of the mouse brain
Oh, S. W., Harris, J. A., Ng, L., Winslow, B., Cain, N., Mihalas, S., Wang, Q., Lau, C., Kuan, L., Henry, A. M., et al. (2014) · Nature · doi:10.1038/nature13186 · Cited by 2,612
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588
From circuits to behaviour in the amygdala
Janak, P. H., & Tye, K. M. (2015) · Nature · doi:10.1038/nature14188 · Cited by 2,011 · cited 2×
“Within the amygdala, information processing and behavioral output occur through highly interconnected subdivisions defined by distinct cell types (Janak and Tye, 2015).”
Neuronal circuits for fear and anxiety
Tovote, P., Fadok, J. P., & Lüthi, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3945 · Cited by 1,786
Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety
Davis, M., Walker, D. L., Miles, L., & Grillon, C. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.109 · Cited by 1,513 · cited 1×
“Many of these peptides have been shown to modulate threat-related behaviors and are thought to allow for complex bidirectional control over a variety of defensive responses (Davis et al., 2010; Bowers et al., 2012).”
Encoding of conditioned fear in central amygdala inhibitory circuits
Ciocchi, S., Herry, C., Grenier, F., Wolff, S. B. E., Letzkus, J. J., Vlachos, I., Ehrlich, I., Sprengel, R., Deisseroth, K., Stadler, M. B., et al. (2010) · Nature · doi:10.1038/nature09559 · Cited by 924
Genetic dissection of an amygdala microcircuit that gates conditioned fear
Haubensak, W., Kunwar, P. S., Cai, H., Ciocchi, S., Wall, N. R., Ponnusamy, R., Biag, J., Dong, H.-W., Deisseroth, K., Callaway, E. M., et al. (2010) · Nature · doi:10.1038/nature09553 · Cited by 840 · cited 6×
“CRF Neurons Are Largely Distinct from Other Populations within the CeAL Electrophysiological recordings in the CeAL during presentations of threat-associated stimuli have revealed two primary response profiles: ‘‘fear-on’’ and ‘‘fear-off’’ neurons (Haubensak et al., 2010).”
InfluentialFear conditioning induces a lasting potentiation of synaptic currents in vitro
McKernan, M. G., & Shinnick-Gallagher, P. (1997) · Nature · doi:10.1038/37605 · Cited by 771
The paraventricular thalamus controls a central amygdala fear circuit
Penzo, M. A., Robert, V., Tucciarone, J., De Bundel, D., Wang, M., Van Aelst, L., Darvas, M., Parada, L. F., Palmiter, R. D., He, M., et al. (2015) · Nature · doi:10.1038/nature13978 · Cited by 506
Self-citationExperience-dependent modification of a central amygdala fear circuit
Li, H., Penzo, M. A., Taniguchi, H., Kopec, C. D., Huang, Z. J., & Li, B. (2013) · Nature Neuroscience · doi:10.1038/nn.3322 · Cited by 497 · cited 14×
“Why do CRF neurons in the CeA undergo synaptic plasticity and selectively respond to fear-predictive stimuli, but not regulate conditioned fear expression? One potential explanation for this observation is that CRF neurons facilitate acquisition through themodulation of Sst neurons, and likely other cell types in the…”
MethodInfluentialCassell, M. D., Gray, T. S., & Kiss, J. Z. (1986) · Journal of Comparative Neurology · doi:10.1002/cne.902460406 · Cited by 297
Regulating anxiety with extrasynaptic inhibition
Botta, P., Demmou, L., Kasugai, Y., Markovic, M., Xu, C., Fadok, J. P., Lu, T., Poe, M. M., Xu, L., Cook, J. M., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4102 · Cited by 192 · cited 2×
“12 Neuron 93, 1–15, January 4, 2017 synaptic GABA release onto PKCd neurons in the CeAL protects against fear generalization (Botta et al., 2015).”
Penzo, M. A., Robert, V., & Li, B. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4166-13.2014 · Cited by 187
Lamsa, K., Heeroma, J. H., & Kullmann, D. M. (2005) · Nature Neuroscience · doi:10.1038/nn1486 · Cited by 158
Micevych, P., Akesson, T., & Elde, R. (1988) · Journal of Comparative Neurology · doi:10.1002/cne.902690306 · Cited by 104
Regev, L., Tsoory, M., Gil, S., & Chen, A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.05.036 · Cited by 93
de Jongh, R., Groenink, L., van der Gugten, J., & Olivier, B. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00468-2 · Cited by 54
Cited by
Basolateral to Central Amygdala Neural Circuits for Appetitive Behaviors
Kim, J., Zhang, X., Muralidhar, S., LeBlanc, S. A., & Tonegawa, S. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.034 · Cited by 458
Organization of valence-encoding and projection-defined neurons in the basolateral amygdala
Beyeler, A., Chang, C.-J., Silvestre, M., Lévêque, C., Namburi, P., Wildes, C. P., & Tye, K. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.097 · Cited by 306
“This may synthesize apparently conflicting studies reporting the role of the CeA in freezing and avoidance (Ciocchi et al., 2010; Davis and Shi, 1999; Duvarci and Pare, 2014; Fadok et al., 2017; Goosens and Maren, 2001; Haubensak et al., 2010; Jimenez and Maren, 2009; Li et al., 2013; Maren and Quirk, 2004; Penzo et a…”
BackgroundReward Inhibits Paraventricular CRH Neurons to Relieve Stress
Yuan, Y., Wu, W., Chen, M., Cai, F., Fan, C., Shen, W., Sun, W., & Hu, J. (2019) · Current Biology · doi:10.1016/j.cub.2019.02.048 · Cited by 151
de Guglielmo, G., Kallupi, M., Pomrenze, M. B., Crawford, E., Simpson, S., Schweitzer, P., Koob, G. F., Messing, R. O., & George, O. (2019) · Nature Communications · doi:10.1038/s41467-019-09183-0 · Cited by 127
Moscarello, J. M., & Penzo, M. A. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01130-5 · Cited by 112
Metadata
- Authors
- Sanford, C. A., Soden, M. E., Baird, M. A., Miller, S. M., Schulkin, J., Palmiter, R. D., Clark, M., & Zweifel, L. S.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 93
- Issue
- 1
- Pages
- 164-178
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2563744755
- Cited by
- 198
- References
- 20
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- bronze
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