CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation
Open accessAbstract
The basolateral nucleus (BLA) of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF). Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatments for stress-related illnesses such as post-traumatic stress disorder.
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The BLA is generally hyperactive following chronic stress.
“The stress-induced attenuation of BLA→DMS activity was surprising because the BLA is, generally, hyperactive following chronic stress54–61 (c.f.62).”
From A dual-pathway architecture for stress to disrupt agency and promote habit (2025) · cites this paper as [54]
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Cites
Contributions of the Amygdala to Emotion Processing: From Animal Models to Human Behavior
Phelps, E. A., & LeDoux, J. E. (2005) · Neuron · doi:10.1016/j.neuron.2005.09.025 · Cited by 3,203 · cited 1× · see citing works
“The amygdala plays a key role in the central processing of stressful or emotionally charged stimuli (Davis, 1992; Phelps and LeDoux, 2005), and in particular, the basolateral complex of the amygdala (BLA) has been shown to mediate emotional arousal (Roozendaal et al.”
BackgroundThe role of the amygdala in fear and anxiety
Davis, M. (1992) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.15.030192.002033 · Cited by 2,357 · see citing works
THE AMYGDALA MODULATES THE CONSOLIDATION OF MEMORIES OF EMOTIONALLY AROUSING EXPERIENCES
McGaugh, J. L. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144157 · Cited by 2,296 · see citing works
Pitkänen, A., Savander, V., & LeDoux, J. E. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01125-9 · Cited by 980 · see citing works
Chalmers, D., Lovenberg, T. W., & Souza, E. D. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-10-06340.1995 · Cited by 925 · see citing works
Reyes, T. M., Lewis, K., Perrin, M. H., Kunitake, K. S., Vaughan, J., Arias, C. A., Hogenesch, J. B., Gulyas, J., Rivier, J., Vale, W. W., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051626398 · Cited by 887 · see citing works
A role for corticotropin releasing factor and urocortin in behavioral responses to stressors
Koob, G. F., & Heinrichs, S. C. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01991-5 · Cited by 530 · see citing works
Thalamoamygdaloid projections in the rat: A test of the amygdala's role in sensory processing
Turner, B. H., & Herkenham, M. (1991) · The Journal of comparative neurology · doi:10.1002/cne.903130208 · Cited by 437 · see citing works
Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders
Holmes, A., Heilig, M. A., Rupniak, N. M. J., Steckler, T., & Griebel, G. (2003) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2003.09.011 · Cited by 401 · see citing works
Muller, J., Corodimas, K. P., Fridel, Z., & LeDoux, J. E. (1997) · Behavioral Neuroscience · doi:10.1037/0735-7044.111.4.683 · Cited by 382 · cited 1× · see citing works
“The BLA receives excitatory input from diverse regions of the CNS, including the thalamus (Blair et al., 2003; Muller et al., 1997; Turner and Herkenham, 1991), lateral entorhinal cortex (Mcdonald and Mascagni, 1997), hippocampus, frontal cortex (Pitkanen et al.”
BackgroundMuller, J., Corodimas, K. P., Fridel, Z., & LeDoux, J. E. (1997) · Behavioral Neuroscience · doi:10.1037//0735-7044.111.4.683 · Cited by 382 · see citing works
Rainnie, D. G., Bergeron, R., Sajdyk, T. J., Patil, M. M., Gehlert, D. R., & Shekhar, A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5740-03.2004 · Cited by 293 · see citing works
Role of the basolateral amygdala in memory consolidation
Paré, D. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00104-7 · Cited by 288 · see citing works
Makino, S., Hashimoto, K., & Gold, P. W. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00791-8 · Cited by 260 · see citing works
Roozendaal, B., Brunson, K. L., Holloway, B. L., McGaugh, J. L., & Baram, T. Z. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212504599 · Cited by 258 · see citing works
Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety
Shekhar, A., Truitt, W., Rainnie, D., & Sajdyk, T. (2005) · Stress · doi:10.1080/10253890500504557 · Cited by 237 · see citing works
Blank, T., Nijholt, I. M., Grammatopoulos, D. K., Randeva, H. S., Hillhouse, E. W., & Spiess, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-02-00700.2003 · Cited by 203 · see citing works
Mascagni, F., McDonald, A. J., & Coleman, J. R. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90016-9 · Cited by 186 · see citing works
Liang, K., & Lee, E. H. Y. (1988) · Psychopharmacology · doi:10.1007/bf00177566 · Cited by 174 · see citing works
Korotkova, T. M., Brown, R. E., Sergeeva, O. A., Ponomarenko, A. A., & Haas, H. L. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04792.x · Cited by 162 · see citing works
Rivier, J., Gulyás, J., Kirby, D., Low, W., Perrin, M. H., Kunitake, K. S., DiGruccio, M. R., Vaughan, J. M., Reubi, J. C., Waser, B., et al. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm0202122 · Cited by 160 · see citing works
Adrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences
Roozendaal, B., Barsegyan, A., & Lee, S. (2007) · Progress in Brain Research · doi:10.1016/s0079-6123(07)67006-x · Cited by 154 · see citing works
Role of the Basolateral Amygdala in Memory Consolidation
McINTYRE, C. K., POWER, A. E., ROOZENDAAL, B., & McGAUGH, J. L. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07088.x · Cited by 147 · see citing works
McDonald, A., & Mascagni, F. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00478-2 · Cited by 142 · see citing works
Presynaptic receptors and the control of glutamate exocytosis
Sánchez‐Prieto, J., Budd, D. C., Herrero, I., Vázquez, E., & Nicholls, D. G. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10031-x · Cited by 134 · see citing works
Liu, J., Yu, B., Neugebauer, V., Grigoriadis, D. E., Rivier, J., Vale, W., Shinnick‐Gallagher, P., & Gallagher, J. P. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5531-03.2004 · Cited by 134 · see citing works
Chapman, P. F., & Bellavance, L. L. (1992) · Synapse · doi:10.1002/syn.890110406 · Cited by 117 · see citing works
Tan, H., Zhong, P., & Yan, Z. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0143-04.2004 · Cited by 112 · see citing works
Rainnie, D. G., Fernhout, B. J. H., & Shinnick‐Gallagher, P. (1992) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)10424-2 · Cited by 108 · see citing works
Electrophysiological actions of corticotropin-releasing factor in the central nervous system.
Siggins, G. R., Gruol, D. L., Aldenhoff, J. B., & Pittman, Q. J. (1985) · PubMed · Cited by 100 · see citing works
McDonald, A., & Mascagni, F. (1996) · Neuroscience · doi:10.1016/0306-4522(95)00416-5 · Cited by 94 · see citing works
Hubbard, D. T., Nakashima, B. R., Lee, I., & Takahashi, L. K. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.10.001 · Cited by 85 · see citing works
Croiset, G., Nijsen, M., & Kamphuis, P. J. G. H. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00556-2 · Cited by 84 · see citing works
A novel mechanism of action of corticotropin releasing factor in rat Leydig cells.
Ulisse, S., Fabbri, A., Tinajero, J. C., & Dufau, M. L. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39926-0 · Cited by 73 · see citing works
Pharmacology and Biology of Corticotropin-Releasing Factor (CRF) Receptors
Eckart, K., Jahn, O., Radulović, J., Radulović, M., Blank, T., Stiedl, O., Brauns, O., Tezval, H., Zeyda, T., & Spiess, J. (2002) · Receptors and Channels · doi:10.1080/10606820213678 · Cited by 67 · see citing works
Wang, H. L., Tsai, L. Y., & Lee, E. H. Y. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.83.1.343 · Cited by 66 · see citing works
Sajdyk, T. J., & Gehlert, D. R. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02638-x · Cited by 52 · see citing works
Isoardi, N. A., Martijena, I. D., Carrer, H. F., & Molina, V. A. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300478 · Cited by 39 · see citing works
Yu, B., & Shinnick‐Gallagher, P. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37223-4 · Cited by 39 · see citing works
Input-specific LTP and depotentiation in the basolateral amygdala
Aroniadou‐Anderjaska, V., Post, R. M., Rogawski, M. A., & Li, H. (2001) · Neuroreport · doi:10.1097/00001756-200103050-00041 · Cited by 34 · see citing works
Associative Plasticity in Neurons of the Lateral Amygdala during Auditory Fear Conditioning
Blair, H. T., Tinkelman, A., Moita, M. A. P., & LeDoux, J. E. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07106.x · Cited by 30 · see citing works
Singewald, N., Zhou, G., Chen, F., & Philippu, A. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12312-0 · Cited by 30 · see citing works
Reisine, T., & Guild, S. (1987) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13028-9 · Cited by 28 · see citing works
Guo, Z., Tellew, J. E., Gross, R. S., Dyck, B. P., Grey, J., Haddach, M., Kiankarimi, M., Lanier, M. C., Li, B.-F., Luo, Z., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050384+ · Cited by 27 · see citing works
Chen, C., & Grigoriadis, D. E. (2005) · Drug Development Research · doi:10.1002/ddr.20025 · Cited by 24 · see citing works
Korotkova, T. M., Brown, R. E., Sergeeva, O. A., Ponomarenko, A. A., & Haas, H. L. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04977.x · Cited by 9 · see citing works
Pharmacology and Biology of Corticotropin-Releasing Factor (CRF) Receptors
Eckart, K., Jahn, O., Radulović, J., et al. (2002) · Receptors and Channels · doi:10.3109/10606820213678 · Cited by 8 · see citing works
Chen, C., & Grigoriadis, D. E. (2006) · ChemInform · doi:10.1002/chin.200636256 · Cited by 3 · see citing works
Bayraktar (2000) · doi:10.1002/(sici)1096-9861(20000508)420:3
Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse
Van Pett, K., Viau, V., Bittencourt, J. C., Chan, R. K. W., Li, H.-Y., Arias, C., Prins, G. S., Perrin, M., Vale, W., & Sawchenko, P. E. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20001211)428:2
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Sandi, C., & Richter‐Levin, G. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.02.004 · Cited by 227 · see citing works
Bruchas, M. R., Land, B. B., Lemos, J. C., & Chavkin, C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008528 · Cited by 204 · see citing works
Kirby, L. G., Freeman-Daniels, E., Lemos, J. C., Nunan, J. D., Lamy, C. M., Akanwa, A. C., & Beck, S. G. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2887-08.2008 · Cited by 107 · see citing works
Bravo, J. A., Dinan, T. G., & Cryan, J. F. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710000994 · Cited by 103 · see citing works
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McCool, B. A. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.12.028 · Cited by 96 · see citing works
Sandi, C., Cordero, M. I., Ugolini, A., Varea, E., Caberlotto, L., & Large, C. H. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06451.x · Cited by 85 · see citing works
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Panguluri, S. K., Saggu, S., & Lundy, R. F. (2009) · Brain Research · doi:10.1016/j.brainres.2009.08.038 · Cited by 30 · see citing works
Kupferschmidt, D., Klas, P., & Erb, S. M. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01983.x · Cited by 29 · see citing works
Donatti, A. F., & Leite‐Panissi, C. R. A. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.06.027 · Cited by 28 · see citing works
Chen, L., Song, L., Cai, J., Wei, T., Liu, L., Zhao, H., Liu, B.-H., Jing, H., Jin, Z., Liu, M., et al. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.10.027 · Cited by 26 · see citing works
Bouchez, G., Millan, M. J., Rivet, J., Billiras, R., Boulanger, R., & Gobert, A. (2012) · Brain Research · doi:10.1016/j.brainres.2012.01.010 · Cited by 24 · see citing works
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Kasahara, M., Groenink, L., Kas, M. J., Bijlsma, E. Y., Olivier, B., & Sarnyai, Z. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.12.029 · Cited by 23 · see citing works
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Ahnaou, A., Raeyemaekers, L., Huysmans, H., & Drinkenburg, W. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.05.035 · Cited by 13 · see citing works
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Tóth, M., Gresack, J. E., Hauger, R. L., Halberstadt, A. L., & Risbrough, V. B. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3114-9 · Cited by 14 · see citing works
Agoglia, A. E., Zhu, M., Ying, R., Sidhu, H., Natividad, L. A., Wolfe, S. A., Buczynski, M. W., Contet, C., Parsons, L. H., Roberto, M., et al. (2020) · eNeuro · doi:10.1523/eneuro.0420-19.2020 · Cited by 13 · see citing works
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A dual-pathway architecture enables chronic stress to disrupt agency and promote habit formationPreprint
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Characterizing the neuropeptide pathways between the forebrain and the pons.
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Hladky, F. (2014) · Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.16956
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Romero, J. M., Stafford-Trujillo, S.-M., Mendoza, M., Chin, P.-S., Srivastava, S., Kochukov, M. Y., Tong, Q., & Arenkiel, B. R. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1876369
- Authors
- Ugolini, A.
- Affiliations
- GlaxoSmithKline (Italy) (IT)
- Corresponding author
- Ugolini, Annarosa
- Venue
- Frontiers in Behavioral Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2008
- Volume
- 2
- Pages
- 2-2
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC2525866
- OpenAlex
- W2081812019
- Cited by
- 32
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 3
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Neurocrine Biosciences
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- CRF1 receptor, corticotropin-releasing factor, basolateral amygdala, neuronal excitability, afferent stimulation, field potentials, urocortin II, protein kinase C, post-traumatic stress disorder, CRF1 receptor antagonist
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