Independent Hypothalamic Circuits for Social and Predator Fear

Overview

Journal Nat Neurosci

Date 2013 Nov 12

PMID 24212674

Citations 114

Authors

Bianca A Silva

Camilla Mattucci

Piotr Krzywkowski

Emanuele Murana

Anna Illarionova

Valery Grinevich

Newton S Canteras

Davide Ragozzino

Cornelius T Gross

Affiliations

Soon will be listed here.

Abstract

The neural circuits mediating fear to naturalistic threats are poorly understood. We found that functionally independent populations of neurons in the ventromedial hypothalamus (VMH), a region that has been implicated in feeding, sex and aggression, are essential for predator and social fear in mice. Our results establish a critical role for VMH in fear and have implications for selective intervention in pathological fear in humans.

Citing Articles

Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats.

Hinds N, Wojtas I, Pulley D, McDonald S, Spencer C, Sudarikov M bioRxiv. 2025; .

PMID: 39896664 PMC: 11785129. DOI: 10.1101/2025.01.22.634146.

Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice.

Nguyen Q, Rocha A, Chhor R, Yamashita Y, Stadler C, Pontrello C Elife. 2024; 12.

PMID: 39412856 PMC: 11483128. DOI: 10.7554/eLife.92982.

How can ethology inform the neuroscience of fear, aggression and dominance?.

Battivelli D, Fan Z, Hu H, Gross C Nat Rev Neurosci. 2024; 25(12):809-819.

PMID: 39402310 DOI: 10.1038/s41583-024-00858-2.

Hypothalamus-sympathetic-liver axis mediates the early phase of stress-induced hyperglycemia in the male mice.

Liu L, Huang Z, Zhang J, Wang M, Yue T, Wang W Nat Commun. 2024; 15(1):8632.

PMID: 39366937 PMC: 11452707. DOI: 10.1038/s41467-024-52815-3.

Periaqueductal gray activates antipredatory neural responses in the amygdala of foraging rats.

Kim E, Kong M, Park S, Cho J, Kim J Elife. 2024; 12.

PMID: 39133827 PMC: 11318971. DOI: 10.7554/eLife.88733.

References

Knobloch H, Charlet A, Hoffmann L, Eliava M, Khrulev S, Cetin A . Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron. 2012; 73(3):553-66. DOI: 10.1016/j.neuron.2011.11.030. View

Ribeiro-Barbosa E, Canteras N, Cezario A, Blanchard R, Blanchard D . An alternative experimental procedure for studying predator-related defensive responses. Neurosci Biobehav Rev. 2005; 29(8):1255-63. DOI: 10.1016/j.neubiorev.2005.04.006. View

Lin D, Boyle M, Dollar P, Lee H, Lein E, Perona P . Functional identification of an aggression locus in the mouse hypothalamus. Nature. 2011; 470(7333):221-6. PMC: 3075820. DOI: 10.1038/nature09736. View

Hsu S, RAINE L . Protein A, avidin, and biotin in immunohistochemistry. J Histochem Cytochem. 1981; 29(11):1349-53. DOI: 10.1177/29.11.6172466. View

Armbruster B, Li X, Pausch M, Herlitze S, Roth B . Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci U S A. 2007; 104(12):5163-8. PMC: 1829280. DOI: 10.1073/pnas.0700293104. View

Kruk M, van der Poel A, Meelis W, Hermans J, Mostert P, Mos J . Discriminant analysis of the localization of aggression-inducing electrode placements in the hypothalamus of male rats. Brain Res. 1983; 260(1):61-79. DOI: 10.1016/0006-8993(83)90764-3. View

Kurrasch D, Cheung C, Lee F, Tran P, Hata K, Ingraham H . The neonatal ventromedial hypothalamus transcriptome reveals novel markers with spatially distinct patterning. J Neurosci. 2007; 27(50):13624-34. PMC: 6673626. DOI: 10.1523/JNEUROSCI.2858-07.2007. View

Wilent W, Oh M, Buetefisch C, Bailes J, Cantella D, Angle C . Induction of panic attack by stimulation of the ventromedial hypothalamus. J Neurosurg. 2009; 112(6):1295-8. DOI: 10.3171/2009.9.JNS09577. View

Pilpel N, Landeck N, Klugmann M, Seeburg P, Schwarz M . Rapid, reproducible transduction of select forebrain regions by targeted recombinant virus injection into the neonatal mouse brain. J Neurosci Methods. 2009; 182(1):55-63. DOI: 10.1016/j.jneumeth.2009.05.020. View

10.

Hancock J, Cadwallader K, PATERSON H, Marshall C . A CAAX or a CAAL motif and a second signal are sufficient for plasma membrane targeting of ras proteins. EMBO J. 1991; 10(13):4033-9. PMC: 453151. DOI: 10.1002/j.1460-2075.1991.tb04979.x. View

11.

Brandao M, Zanoveli J, Ruiz-Martinez R, Oliveira L, Landeira-Fernandez J . Different patterns of freezing behavior organized in the periaqueductal gray of rats: association with different types of anxiety. Behav Brain Res. 2007; 188(1):1-13. DOI: 10.1016/j.bbr.2007.10.018. View

12.

Canteras N . The medial hypothalamic defensive system: hodological organization and functional implications. Pharmacol Biochem Behav. 2002; 71(3):481-91. DOI: 10.1016/s0091-3057(01)00685-2. View

13.

Szymczak A, Workman C, Wang Y, Vignali K, Dilioglou S, Vanin E . Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nat Biotechnol. 2004; 22(5):589-94. DOI: 10.1038/nbt957. View

14.

Canteras N, Simerly R, Swanson L . Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol. 1994; 348(1):41-79. DOI: 10.1002/cne.903480103. View

15.

Berton O, McClung C, DiLeone R, Krishnan V, Renthal W, Russo S . Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science. 2006; 311(5762):864-8. DOI: 10.1126/science.1120972. View

16.

Gross C, Canteras N . The many paths to fear. Nat Rev Neurosci. 2012; 13(9):651-8. DOI: 10.1038/nrn3301. View

17.

Simerly R . Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci. 2002; 25:507-36. DOI: 10.1146/annurev.neuro.25.112701.142745. View

18.

Dhillon H, Zigman J, Ye C, Lee C, McGovern R, Tang V . Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron. 2006; 49(2):191-203. DOI: 10.1016/j.neuron.2005.12.021. View

19.

Motta S, Goto M, Gouveia F, Baldo M, Canteras N, Swanson L . Dissecting the brain's fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders. Proc Natl Acad Sci U S A. 2009; 106(12):4870-5. PMC: 2660765. DOI: 10.1073/pnas.0900939106. View

20.

Alexander G, Rogan S, Abbas A, Armbruster B, Pei Y, Allen J . Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron. 2009; 63(1):27-39. PMC: 2751885. DOI: 10.1016/j.neuron.2009.06.014. View