Mapping the Neural Circuitry of Predator Fear in the Nonhuman Primate

Overview

Journal Brain Struct Funct

Specialty Neurology

Date 2020 Dec 2

PMID 33263778

Citations 10

Authors

Quentin Montardy

William C Kwan

Inaki C Mundinano

Dylan M Fox

Liping Wang

Cornelius T Gross

James A Bourne

Affiliations

Soon will be listed here.

Abstract

In rodents, innate and learned fear of predators depends on the medial hypothalamic defensive system, a conserved brain network that lies downstream of the amygdala and promotes avoidance via projections to the periaqueductal gray. Whether this network is involved in primate fear remains unknown. To address this, we provoked flight responses to a predator (moving snake) in the marmoset monkey under laboratory conditions. We combined c-Fos immunolabeling and anterograde/retrograde tracing to map the functional connectivity of the ventromedial hypothalamus, a core node in the medial hypothalamic defensive system. Our findings demonstrate that the ventromedial hypothalamus is recruited by predator exposure in primates and that anatomical connectivity of the rodent and primate medial hypothalamic defensive system are highly conserved.

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References

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

Koutsikou S, Apps R, Lumb B . Top down control of spinal sensorimotor circuits essential for survival. J Physiol. 2017; 595(13):4151-4158. PMC: 5491858. DOI: 10.1113/JP273360. View

Kunwar P, Zelikowsky M, Remedios R, Cai H, Yilmaz M, Meister M . Ventromedial hypothalamic neurons control a defensive emotion state. Elife. 2015; 4. PMC: 4379496. DOI: 10.7554/eLife.06633. View

LeDoux J . Rethinking the emotional brain. Neuron. 2012; 73(4):653-76. PMC: 3625946. DOI: 10.1016/j.neuron.2012.02.004. 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

Rufino R, Mota-Ortiz S, de Lima M, Baldo M, Canteras N . The rostrodorsal periaqueductal gray influences both innate fear responses and acquisition of fear memory in animals exposed to a live predator. Brain Struct Funct. 2019; 224(4):1537-1551. DOI: 10.1007/s00429-019-01852-6. View

Barros M, Boere V, Huston J, Tomaz C . Measuring fear and anxiety in the marmoset (Callithrix penicillata) with a novel predator confrontation model: effects of diazepam. Behav Brain Res. 2000; 108(2):205-11. DOI: 10.1016/s0166-4328(99)00153-9. View

Kim E, Horovitz O, Pellman B, Tan L, Li Q, Richter-Levin G . Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear responses in rats. Proc Natl Acad Sci U S A. 2013; 110(36):14795-800. PMC: 3767534. DOI: 10.1073/pnas.1310845110. View

Pessoa L, Adolphs R . Emotion processing and the amygdala: from a 'low road' to 'many roads' of evaluating biological significance. Nat Rev Neurosci. 2010; 11(11):773-83. PMC: 3025529. DOI: 10.1038/nrn2920. View

10.

Paul C, Beltz B, Berger-Sweeney J . Staining for acetylcholinesterase in brain sections. Cold Spring Harb Protoc. 2010; 2010(8):pdb.prot4806. DOI: 10.1101/pdb.prot4806. View

11.

Carr J . I'll take the low road: the evolutionary underpinnings of visually triggered fear. Front Neurosci. 2015; 9:414. PMC: 4624861. DOI: 10.3389/fnins.2015.00414. View

12.

Miller C, Freiwald W, Leopold D, Mitchell J, Silva A, Wang X . Marmosets: A Neuroscientific Model of Human Social Behavior. Neuron. 2016; 90(2):219-33. PMC: 4840471. DOI: 10.1016/j.neuron.2016.03.018. View

13.

Feinstein J, Adolphs R, Damasio A, Tranel D . The human amygdala and the induction and experience of fear. Curr Biol. 2010; 21(1):34-8. PMC: 3030206. DOI: 10.1016/j.cub.2010.11.042. View

14.

Maior R, Hori E, Barros M, Teixeira D, Tavares M, Ono T . Superior colliculus lesions impair threat responsiveness in infant capuchin monkeys. Neurosci Lett. 2011; 504(3):257-60. DOI: 10.1016/j.neulet.2011.09.042. View

15.

Martinez R, Carvalho-Netto E, Ribeiro-Barbosa E, Baldo M, Canteras N . Amygdalar roles during exposure to a live predator and to a predator-associated context. Neuroscience. 2010; 172:314-28. DOI: 10.1016/j.neuroscience.2010.10.033. View

16.

Wei P, Liu N, Zhang Z, Liu X, Tang Y, He X . Processing of visually evoked innate fear by a non-canonical thalamic pathway. Nat Commun. 2015; 6:6756. PMC: 4403372. DOI: 10.1038/ncomms7756. View

17.

Silva B, Mattucci C, Krzywkowski P, Cuozzo R, Carbonari L, Gross C . The ventromedial hypothalamus mediates predator fear memory. Eur J Neurosci. 2016; 43(11):1431-9. PMC: 4899089. DOI: 10.1111/ejn.13239. View

18.

Krieger M, Conrad L, Pfaff D . An autoradiographic study of the efferent connections of the ventromedial nucleus of the hypothalamus. J Comp Neurol. 1979; 183(4):785-815. DOI: 10.1002/cne.901830408. View

19.

Feinstein J, Buzza C, Hurlemann R, Follmer R, Dahdaleh N, Coryell W . Fear and panic in humans with bilateral amygdala damage. Nat Neurosci. 2013; 16(3):270-2. PMC: 3739474. DOI: 10.1038/nn.3323. View

20.

Faul L, Stjepanovic D, Stivers J, Stewart G, Graner J, Morey R . Proximal threats promote enhanced acquisition and persistence of reactive fear-learning circuits. Proc Natl Acad Sci U S A. 2020; 117(28):16678-16689. PMC: 7369317. DOI: 10.1073/pnas.2004258117. View