Ventromedial hypothalamic neurons control a defensive emotion state

eLife

Volumn 2015, Issue 4, 2015, Pages

  Kunwar, Prabliat S ^a   Zelikowsky, Moriel ^a   Remedios, Ryan ^a   Cai, Haijiang ^a   Yilmaz, Melis ^a   Meister, Markus ^a   Anderson, David J ^a,b  

^a California Institute of Technology HHMI   (United States)

^b CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOSTERONE; STEROIDOGENIC FACTOR 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AVOIDANCE BEHAVIOR; BEHAVIOR CONTROL; BRAIN ELECTROPHYSIOLOGY; CELL COUNTING; CONTROLLED STUDY; EMOTION; EXPERIMENTAL ANXIETY TEST; EXPERIMENTAL SOCIAL BEHAVIOR TEST; FEEDING BEHAVIOR; HYPOTHALAMUS VENTROMEDIAL NUCLEUS; IMMUNOHISTOLOGY; MALE; MOUSE; NONHUMAN; OPTOGENETICS; PHOTOSTIMULATION; PLACE PREFERENCE; PREDATOR AVOIDANCE; SCORING SYSTEM; STEREOTAXIC SURGERY; VISUAL STIMULATION; ANIMAL; ANIMAL BEHAVIOR; ANXIETY; C57BL MOUSE; CATALEPSY; CONDITIONED REFLEX; CYTOLOGY; FEAR; GENETICS; IMMUNOHISTOCHEMISTRY; LONG EVANS RAT; MEMORY; METABOLISM; NERVE CELL; NERVE TRACT; PHOTOACOUSTICS; PHYSIOLOGY; PREDATION; PSYCHOLOGY; TRANSGENIC MOUSE;

ANIMALS; ANXIETY; AVOIDANCE LEARNING; BEHAVIOR, ANIMAL; CONDITIONING, CLASSICAL; EMOTIONS; FEAR; FREEZING REACTION, CATALEPTIC; IMMUNOHISTOCHEMISTRY; MEMORY; MICE, INBRED C57BL; MICE, TRANSGENIC; NEURAL PATHWAYS; NEURONS; PHOTOACOUSTIC TECHNIQUES; PREDATORY BEHAVIOR; RATS, LONG-EVANS; STEROIDOGENIC FACTOR 1; VENTROMEDIAL HYPOTHALAMIC NUCLEUS;

EID: 84924308700     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.06633     Document Type: Article

References (123)

1. Adamec, R, Walling, S, and Burton, P. 2004. Long-lasting, selective, anxiogenic effects of feline predator stress in mice. Physiology & behavior 83, 401-410. doi: 10.1016/j.physbeh.2004.08.029.
2. Adolphs, R. 2010. Emotion. Curr Biol 20, R549-552. doi: 10.1016/j.cub.2010.05.046.
3. Adolphs, R. 2013. Thebiology offear. Curr Biol 23, R79-93. doi: 10.1016/j.cub.2012.11.055.
4. Allen, MJ, Godenschwege, TA, Tanouye, MA, and Phelan, P. 2006. Making an escape: development and function of the Drosophila giant fibre system. Semin Cell Dev Biol 77, 31-41. doi: 10.1016/j.semcdb.2005.11.011.
5. Amano, K, Tanikawa, T, Kawamura, H, Iseki, H, Notani, M, Kawabatake, H, Shiwaku, T, Suda, T, Demura, H, and Kitamura, K. 1982. Endorphins and pain relief. Further observations on electrical stimulation of the lateral part of the periaqueductal gray matter during rostral mesencephalic reticulotomy for pain relief. Appl Neurophysiol 45, 123-135. doi
6. Anderson, DJ, and Adolphs, R. 2014. A framework for studying emotions across species. Cell 157, 187-200. doi: 10.1016/j.cell.2014.03.003.
7. Anisman, H, and Waller, TG. 1973. Footshock-produced excitation and inhibition of activity in rats. Animal Learning & Behavior 1, 93-95. doi
8. Anthony, TE, Dee, N, Bernard, A, Lerchner, W, Heintz, N, and Anderson, DJ. 2014. Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit. Cell 156, 522-536. doi: 10.1016/j.cell.2013.12.040.
9. Aravanis, AM, Wang, LP, Zhang, F, Meltzer, LA, Mogri, MZ, Schneider, MB, and Deisseroth, K. 2007. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetictechnology. JNeural Eng 4, S143-156. doi: 10.1088/1741- 2560/4/3/S02.
10. Aschauer, DF, Kreuz, S, and Rumpel, S.2013. Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain. PLoS One 8, e76310. doi: 10.1371/joumal.pone.0076310.
11. Bergan, JF, Ben-Shaul, Y, and Dulac, C. 2014. Sex-specific processing of social cues in the medial amygdala. Elife 3, e02743. doi: 10.7554/eLife.02743.
12. Bester, H, Besson, JM, and Bernard, JF. 1997. Organization of efferent projections from the parabrachial area to the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol 383, 245-281. doi
13. Bittencourt, AS, Nakamura-Palacios, EM, Mauad, H, Tufik, S, and Schenberg, LC. 2005. Organization of electrically and chemically evoked defensive behaviors within the deeper collicular layers as compared to the periaqueductal gray matter of the rat. Neuroscience 133, 873-892. doi: 10.1016/j.neuroscience.2005.03.012.
14. Blanchard, DC, Blanchard, RJ, and Griebel, G. 2005. Defensive responses to predator threat in the rat and mouse. Curr Protoc Neurosci Chapter 8, Unit 8 19. doi: 10.1002/0471142301.ns0819s30.
15. Blanchard, DC, Griebel, G, and Blanchard, RJ. 2001. Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic. Neuroscience & Biobehavioral Reviews 25, 205-218. doi
16. Blanchard, DC, Griebel, G, and Blanchard, RJ. 2003a. The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic. Europeanjoumal of pharmacology 463, 97-116. doi
17. Blanchard, DC, Li, Cl, Hubbard, D, Markham, CM, Yang, M, Takahashi, LK, and Blanchard, RJ. 2003b. Dorsal premammillary nucleus differentially modulates defensive behaviors induced by different threat stimuli in rats. Neurosci Lett 345, 145-148. doi
18. Blanchard, RJ, and Blanchard, DC (1989a). Antipredator defensive behaviors in a visible burrow system. In J Comp Psychol, pp. 70-82.
19. Blanchard, RJ, and Blanchard, DC (1989b). Attack and defense in rodents as ethoexperimental models for the study of emotion. In Prog Neuropsychopharmacol Biol Psychiatry, pp. S3-14.
20. Blanchard, RJ, Blanchard, DC, Rodgers, J, and Weiss, SM. 1990. The characterization and modelling of antipredator defensive behavior. Neurosci Biobehav Rev 14, 463-472. doi
21. Blanchard, RJ, Hebert, MA, Ferrari, PF, Ferrari, P, Palanza, P, Figueira, R, Blanchard, DC, and Parmigiani, S. 1998. Defensive behaviors in wild and laboratory (Swiss) mice: the mouse defense test battery. Physiology & Behavior 65, 201-209. doi
22. Bolles, RC. 1970. Species-specific defense reactions and avoidance learning. Psychological Review 77, 32-48. doi
23. Bolles, RC, and Riley, AL. 1973. Freezing as an Avoidance Response: Another Look at the Operant-Respondent Distinction. Learning and Motivation 4, 268-275. doi
24. Boyden, ES, Zhang, F, Bamberg, E, Nagel, G, and Deisseroth, K. 2005. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8, 1263-1268. doi
25. Brandao, ML, de Aguiar, JC, and Graeff, FG. 1982. GABA mediation of the anti-aversive action of minor tranquilizers. Pharmacol Biochem Behav 16, 397-402. doi
26. Brandao, ML, Di Scala, G, Bouchet, MJ, and Schmitt, P. 1986. Escape behavior produced by the blockade of glutamic acid decarboxylase (GAD) in mesencephalic central gray or medial hypothalamus. Pharmacol Biochem Behav 24, 497-501. doi
27. Cai, H, Haubensak, W, Anthony, TE, and Anderson, DJ. 2014. Central amygdala PKC-delta(+) neurons mediate the influence of multiple anorexigenic signals. Nat Neurosci 17, 1240-1248. doi: 10.1038/nn.3767.
28. Cannon, WB. 1927. The James-Lange theory of emotions: a critical examination and an alternative theory. Am J Psychol 39, 106-124. doi
29. Canteras, NS. 2002. The medial hypothalamic defensive system: hodological organization and functional implications. Pharmacol Biochem Behav 71, 481-491. doi
30. Canteras, NS, Chiavegatto, S, Ribeiro do Valle, LE, and Swanson, LW. 1997. Severe reduction of rat defensive behavior to a predator by discrete hypothalamic chemical lesions. Brain Res Bull 44, 297-305. doi
31. Canteras, NS, Simerly, RB, and Swanson, LW. 1994. Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol 348, 41-79. doi: 10.1002/cne.903480103.
32. Cezario, AF, Ribeiro-Barbosa, ER, Baldo, MV, and Canteras, NS. 2008. Hypothalamic sites responding to predator threats-the role of the dorsal premammillary nucleus in unconditioned and conditioned antipredatory defensive behavior. Eur J Neurosci 28, 1003-1015. doi: 10.1111/j.l460-9568.2008.06392.x.
33. Cohen, BD, Brown, GW, and Brown, ML. 1957. Avoidance learning motivated by hypothalamic stimulation. J Exp Psychol 53, 228-233. doi
34. Colpaert, FC. 1975. The ventromedial hypothalamus and the control of avoidance behavior and aggression: fear hypothesis versus response-suppression theory oflimbic system function. Behavioral Biology 15, 27-44. doi
35. Colpaert, FC, and Wiepkema, PR. 1976. Brief communication ventromedial hypothalamus: fear conditioning and passive avoidance in rats. Physiology & behavior 16, 91-95. doi
36. Darwin, C (1872). The Expression of the Emotions in Man and Animals, 3rd edn (Oxford: Oxford University Press).
37. Davis, M. 1992. The role of the amygdala in fear and anxiety. Annu Rev Neurosci 15, 353-375. doi:10.1146/annurev.ne.l5.030192.002033.
38. Davis, M, Walker, DL, Miles, L, and Grillon, C. 2010. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105-135. doi: 10.1038/npp.2009.109.
39. Dhillon, H, Zigman, JM, Ye, C, Lee, CE, McGovern, RA, Tang, V, Kenny, CD, Christiansen, LM, White, RD, Edelstein, EA, et al. 2006. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49, 191-203. doi: S0896-6273(05)01134-7 [pii] 10.1016/j.neuron.2005.12.021.
40. Di Scala, G, Mana, MJ, Jacobs, WJ, and Phillips, AG. 1987. Evidence of Pavlovian conditioned fear following electrical stimulation of the periaqueductal grey in the rat. Physiology & behavior 40, 55-63. doi
41. Di Scala, G, and Sandner, G. 1989. Conditioned place aversion produced by microinjections of semicarbazide into the periaqueductal gray of the rat. Brain Res 483, 91-97. doi
42. Dielenberg, RA, Hunt, GE, and McGregor, IS. 2001. "When a rat smells a cat": the distribution of Fos immunoreactivity in rat brain following exposure to a predatory odor. Neuroscience 104, 1085-1097. doi
43. Dong, HW, and Swanson, LW. 2004. Projections from bed nuclei of the stria terminalis, posterior division: implications for cerebral hemisphere regulation of defensive and reproductive behaviors. J Comp Neurol 471, 396-433. doi: 10.1002/cne.20002.
44. Estes, WK, and Skinner, BF. 1941. Some quantitative properties of anxiety. Journal of Experimental Psychology 29, 390-400. doi
45. Fanselow, MS (1982). The postshock activity burst. In Animal Learning & Behavior (Springer), pp. 448-454.
46. Fanselow, MS. 1994. Neural organization of the defensive behavior system responsible for fear. Psychonomic Bulletin & Review 1, 429-438. doi
47. Fanselow, MS, and LeDoux, JE. 1999. Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron 23, 229-232. doi
48. Fanselow, MS, and Lester, LS (1988). functional behavioristic approach to aversively motivated behavior: Predatory imminence as a determinant of the topography of defensive behavior. In In Evolution and Learning, R.C. Bolles, and M.D. Beecher, eds. (Earlbaum), pp. 185-211.
49. Freitas, RL, Uribe-Mariño, A, Castiblanco-Urbina, MA, Elias-Filho, DH, and Coimbra, NC. 2009. GABA(A) receptor blockade in dorsomedial and ventromedial nuclei of the hypothalamus evokes panic-like elaborated defensive behaviour followed by innate fear-induced antinociception. Brain Research 1305, 118-131. doi: 10.1016/j.brainres.2009.09.096.
50. Gallagher, M, and Chiba, AA. 1996. The amygdala and emotion. Curr Opin Neurobiol 6,221227. doi
51. Goldman, M, Compte, A, and Wang, X-J. 2007. Neural Integrators: recurrent mechanisms and models.New Encyclopedia of Neuroscience, 1-26. doi
52. Gomes, FV, Kakihata, AM, Semedo, AC, Hott, SC, Uliana, DL, Guimaraes, FS, and Resstel, LB. 2014. D-cycloserine injected into the dorsolateral periaqueductal gray induces anxiolytic-like effectsinrats. Behav Brain Res 271, 374-379. doi: 10.1016/j.bbr.2014.06.009.
53. Gordon, JA, and Hen, R. 2004. Genetic approaches to the study of anxiety. Annu Rev Neurosci 27, 193-222. doi: 10.1146/annurev.neuro.27.070203.144212.
54. Gross, CT, and Canteras, NS. 2012. The many paths to fear. Nat Rev Neurosci 13, 651-658. doi: 10.1038/nrn3301.
55. Grossman, SP (1970). Avoidance behavior and aggression in rats with transections of the lateral connections of the medial or lateral hypothalamus. In Physiology & behavior (Elsevier), pp. 1103-1108.
56. Grossman, SP. 1972. Aggression, avoidance, and reaction to novel environments in female rats with ventromedial hypothalamic lesions. Journal of comparative and physiological psychology 78, 274-283. doi
57. Haubensak, W, Kunwar, PS, Cai, H, Ciocchi, S, Wall, NR, Ponnusamy, R, Biag, J, Dong, HW, Deisseroth, K, Callaway, EM, et al. 2010. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468, 270-276. doi: nature09553 [pii] 10.1038/nature09553.
58. Hong, W, Kim, DW, and Anderson, DJ. 2014. Antagonistic control of social versus repetitive self-grooming behaviors by separable amygdala neuronal subsets. Cell 158, 1348-1361. doi: 10.1016/j.cell.2014.07.049.
59. Kandel, ER, Schwarts, JH, Jessell, TM, Siegelbaum, SA, and Hudspeth, AJ (2013). Principles of Neural Science, 5th edn (New York: McGraw-Hill).
60. Kiernan, MJ, Westbrook, RF, and Cranney, J. 1995. Immediate shock, passive avoidance, and potentiated startle: Implications for the unconditioned response to shock. Animal Learning & Behavior 23, 22-30. doi
61. Kim, SY, Adhikari, A, Lee, SY, Marshel, JH, Kim, CK, Mallory, CS, Lo, M, Pak, S, Mattis, J, Lim, BK, et al. 2013. Diverging neural pathways assemble a behavioural state from separable features in anxiety. Nature 496, 219-223. doi: 10.1038/naturel2018.
62. Kincheski, GC, Mota-Ortiz, SR, Pavesi, E, Canteras, NS, and Carobrez, AP. 2012. The dorsolateral periaqueductal gray and its role in mediating fear learning to life threatening events. PLoS One 7, e50361. doi: 10.1371/journal.pone.0050361.
63. Kvitsiani, D, Ranade, S, Hangya, B, Taniguchi, H, Huang, JZ, and Kepecs, A. 2013. Distinct behavioural and network correlates of two interneuron types in prefrontal cortex. Nature 498, 363-366. doi: 10.1038/naturel2176.
64. Lammers, JHCM, Kruk, MR, Meelis, W, and van der Poel, AM (1988). Hypothalamic substrates for brain stimulation-induced patterns oflocomotion and escape jumps in the rat. In Brain Research, pp. 294-310.
65. LeDoux, J. 2003. The emotional brain, fear, and the amygdala. Cell Mol Neurobiol 23, 727-738. doi
66. LeDoux, J. 2012. Rethinking the emotional brain. Neuron 73, 653-676. doi: 10.1016/j.neuron.2012.02.004.
67. LeDoux, JE. 1995. Emotion: clues from the brain. Annu Rev Psychol 46, 209-235. doi: 10.1146/annurev.ps.46.020195.001233.
68. LeDoux, JE (1996). The Emotional Brain (New York: Simon and Schuster).
69. LeDoux, JE. 2000. Emotion circuits in the brain. Annu Rev Neurosci 23, 155-184. doi
70. LeDoux, JE. 2014. Coming to terms with fear. Proceedings of the National Academy of Sciences ofthe United States of America 111, 2871-2878. doi: 10.1073/pnas.l400335111.
71. LeDoux, JE, and Damasio, AR (2013). Emotions and Feelings. In Principles of Neural Science, E.R. Kandel, J.H. Schwartz, T.M. Jessell, S.A. Siegelbaum, and A.J. Hudspeth, eds. (New York: McGraw-Hill), pp. 1079-1094.
72. Lee, H, Kim, DW, Remedios, R, Anthony, TE, Chang, A, Madisen, L, Zeng, H, and Anderson, DJ. 2014. Scalable control of mounting and attack by Esrl+ neurons in the ventromedial hypothalamus. Nature 509, 627-632. doi: 10.1038/naturel3169.
73. Lin, D, Boyle, MP, Dollar, P, Lee, H, Lein, ES, Perona, P, and Anderson, DJ. 2012. Functional identification of an aggression locus in the mouse hypothalamus. Nature 470, 221-226. doi: 10.1038/nature09736.
74. Lipp, HP, and Hunsperger, RW. 1978. Threat, attack and flight elicited by electrical stimulation of the ventromedial hypothalamus of the marmoset monkey Callithrixjacchus. Brain Behav Evol 15, 260-293. doi
75. Luo, L, Callaway, EM, and Svoboda, K. 2008. Genetic dissection of neural circuits. Neuron 57, 634-660. doi: 10.1016/j.neuron.2008.01.002.
76. Maier, SF, and Watkins, LR. 2005. Stressor controllability and learned helplessness: the roles oí the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neuroscience & Biobehavioral Reviews 29, 829-841. doi: 10.1016/j.neubiorev.2005.03.021.
77. Major, G, and Tank, D. 2004. Persistent neural activity: prevalence and mechanisms. Curr Opin Neurobiol 14, 675-684. doi: 10.1016/j.conb.2004.10.017.
78. Maren, S, and Fanselow, MS. 1996. The amygdala and fear conditioning: has the nut been cracked? Neuron 16, 237-240. doi
79. Martinez, R, Carvalho-Netto, E, Amaral, V, Nunes-de-Souza, R, and Canteras, N (2008). Investigation of the hypothalamic defensive system in the mouse. In Behav Brain Res, pp. 185-190.
80. Martinez, RC, Carvalho-Netto, EF, Ribeiro-Barbosa, ER, Baldo, MV, and Canteras, NS. 2011. Amygdalar roles during exposure to a live predator and to a predator-associated context. Neuroscience 172, 314-328. doi: 10.1016/j.neuroscience.2010.10.033.
81. Masserman, JH (1941). Is the hypothalamus a center of emotion? In Psychosomatic Medicine.
82. McNaughton, N, and Corr, PJ. 2004. A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance. Neurosci Biobehav Rev 28, 285-305. doi: 10.1016/j.neubiorev.2004.03.005.
83. Mobbs, D, Petrovic, P, Marchant, JL, Hassabis, D, Weiskopf, N, Seymour, B, Dolan, RJ, and Frith, CD (2007). When Fear Is Near: Threat Imminence Elicits Prefrontal-Periaqueductal Gray Shifts in Humans. In Science, pp. 1079-1083.
84. Oh, SW, Harris, JA, Ng, L, Winslow, B, Cain, N, Mihalas, S, Wang, Q, Lau, C, Kuan, L, Henry AM, et al. 2014. A mesoscale connectome of the mouse brain. Nature 508, 207-214. doi: 10.1038/naturel3186.
85. Pagani, JH, and Rosen, JB. 2009. The medial hypothalamic defensive circuit and 2,5-dihydro- 2,4,5-trimethylthiazoline (TMT) induced fear: comparison of electrolytic and neurotoxic lesions Brain Res 1286, 133-146. doi: 10.1016/j.brainres.2009.06.062.
86. Panksepp, J (1998). Affective Neuroscience (New York: Oxford University Press).
87. Panksepp, J. 2011a. The basic emotional circuits of mammalian brains: Do animals have affective lives? Neuroscience & Biobehavioral Reviews 35, 1791-1804. doi: 10.1016/j.neubiorev.2011.08.003.
88. Panksepp, J. 2011b. Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals. PLoS ONE 6, e21236. doi: 10.1371/journal.pone.0021236.g005.
89. Papes, F, Logan, DW, and Stowers, L. 2010. The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141, 692-703. doi: 10.1016/j.cell.2010.03.037.
90. Pavesi, E, Canteras, NS, and Carobrez, AP. 2011. Acquisition of Pavlovian fear conditioning using beta-adrenoceptor activation of the dorsal premammillary nucleus as an unconditioned stimulus to mimic live predator-threat exposure. Neuropsychopharmacology 36, 926-939. doi: 10.1038/npp.2010.231.
91. Pessoa, L, and Adolphs, R. 2010. Emotion processing and the amygdala: from a 'low road' to 'many roads' of evaluating biological significance. Nat Rev Neurosci 11, 773-783. doi: 10.1038/nrn2920.
92. Petrovich, GD, Canteras, NS, and Swanson, LW. 2001. Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems. Brain Res Brain Res Rev 38, 247289. doi
93. Petrovich, GD, Ross, CA, Mody, P, Holland, PC, and Gallagher, M. 2009. Central, but not basolateral, amygdala is critical for control of feeding by aversive learned cues. J Neurosci 29, 15205-15212. doi: 10.1523/JNEUROSCI.3656-09.2009.
94. Phelps, EA, and LeDoux, JE. 2005. Contributions of the amygdala to emotion processing: from animalmodelstohumanbehavior. Neuron 48, 175-187. doi: 10.1016/j.neuron.2005.09.025.
95. Posner, J, Russell, JA, and Peterson, BS. 2005. The circumplex model of affect: an integrative approach to affective neuroscience, cognitive development, and psychopathology. Dev Psychopathol 17, 715-734. doi: 10.1017/S0954579405050340.
96. Ragan, T, Kadiri, LR, Venkataraju, KU, Bahlmann, K, Sutin, J, Taranda, J, Arganda-Carreras, I, Kim, Y, Seung, HS, and Osten, P. 2012. Serial two-photon tomography for automated ex vivo mouse brain imaging. Nature methods 9, 255-258. doi: 10.1038/nmeth.l854.
97. Risold, PY, Canteras, NS, and Swanson, LW. 1994. Organization of projections from the anterior hypothalamic nucleus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol 348, 1-40. doi: 10.1002/cne.903480102.
98. Roberts, WW. 1958. Rapid escape learning without avoidance learning motivated by hypothalamic stimulation in cats. J Comp Physiol Psychol 51, 391-399. doi
99. Rosen, JB. 2004. The neurobiology of conditioned and unconditioned fear: a neurobehavioral system analysis of the amygdala. Behavioral and cognitive neuroscience reviews 3, 23-41. doi: 10.1177/1534582304265945.
100. Russell, JA. 2003. Core affect and the psychological construction of emotion. Psychol Rev 110, 145-172. doi
101. Santos, J, and Brandao, M.2011. GABAergic mechanisms of anterior and ventromedial hypothalamic nuclei in the expression of freezing in response to a light-conditioned stimulus. Psychology and Neuroscience 4, 211-217. doi: 10.3922/j.psns.2011.2.006.
102. Santos, JM, Macedo, CE, and Brandao, ML. 2008. Gabaergic mechanisms ofhypothalamic nuclei in the expression of conditioned fear. Neurobiology of learning and memory 90, 560-568. doi: 10.1016/j.nlm.2008.06.007.
103. Saper, CB, and Lowell, BB. 2014. The hypothalamus. Curr Biol 24, R1111-1116. doi: 10.1016/j.cub.2014.10.023.
104. Silva, BA, Mattucci, C, Krzywkowski, P, Murana, E, Illarionova, A, Grinevich, V, Canteras, NS, Ragozzino, D, and Gross, CT. 2013. Independent hypothalamic circuits for social and predator fear.Natureneuro science 16, 1731-1733. doi: 10.1038/nn.3573.
105. Silveira, MC, and Graeff, FG. 1992. Defense reaction elicited by microinjection ofkainic acid into the medial hypothalamus of the rat: antagonism by a GABAA receptor agonist. Behav Neural Biol 57, 226-232. doi
106. Simon, P, Dupuis, R, and Costentin, J. 1994. Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions. Behav Brain Res 61, 59-64. doi
107. Stamatakis, AM, and Stuber, GD. 2012. Optogenetic strategies to dissectthe neural circuits that underlie reward and addiction. Cold Spring Harb Perspect Med 2. doi: 10.1101/cshperspect.a011924.
108. Sternson, SM. 2013. Hypothalamic survival circuits: blueprints for purposive behaviors. Neuron 77, 810-824. doi: 10.1016/j.neuron.2013.02.018.
109. Stowers, L, Cameron, P, and Keller, JA. 2013. Ominous odors: olfactory control ofinstinctive fear and aggression in mice. Curr Opin Neurobiol 23, 339-345. doi: 10.1016/j.conb.2013.01.007.
110. Sukikara, MH, Mota-Ortiz, SR, Baldo, MV, Felicio, LF, and Canteras, NS. 2010. The periaqueductal gray and its potential role in maternal behavior inhibition in response to predatory threats. Behav Brain Res 209, 226-233. doi: 10.1016/j.bbr.2010.01.048.
111. Swanson, LW. 2005. Anatomy of the soul as reflected in the cerebral hemispheres: neural circuits underlying voluntary control ofbasic motivated behaviors. J Comp Neurol 493, 122-131. doi
112. Turner, SG, Sechzer, JA, and Liebelt, RA. 1967. Sensitivity to electric shock after ventromedial hypothalamic lesions. Experimental neurology 19, 236-244. doi
113. Tye, KM, and Deisseroth, K. 2012. Optogenetic investigation of neural circuits underlying brain disease in animal models. Nature reviews Neuroscience 13, 251-266. doi: 10.1038/nrn3171.
114. Vianna, DM, Graeff, FG, Brandao, ML, and Landeira-Fernandez, J. 2001. Defensive freezing evoked by electrical stimulation of the periaqueductal gray: comparison between dorsolateral and ventrolateral regions. Neuroreport 12, 4109-4112. doi
115. Wada, JA, and Matsuda, M. 1970. Can hypothalamically induced escape behavior be conditioned? Exp Neurol 28, 507-512. doi
116. Wehner, JM, and Radcliffe, RA. 2004. Cued and contextual fear conditioning in mice. Curr Protoc Neurosci Chapter 8, Unit 8 5C. doi: 10.1002/0471142301.ns0805cs27.
117. Weisman, RN, and Hamilton, LW. 1972. Two-way avoidance responding following VMH lesions: effects of varying shock intensity. Physiology & behavior 9, 243-246. doi
118. Wilent, WB, Oh, MY, Buetefisch, C, Bailes, JE, Cantella, D, Angle, C, and Whiting, DM. 2011. Mapping of microstimulation evoked responses and unit activity patterns in the lateral hypothalamic area recorded in awake humans. Technical note. J Neurosurg 115, 295-300. doi: 10.3171/2011.3.JNS101574.
119. Wilent, WB, Oh, MY, Buetefisch, CM, Bailes, JE, Cantella, D, Angle, C, and Whiting, DM. 2010. Induction of panic attack by stimulation of the ventromedial hypothalamus. J Neurosurg 112, 1295-1298. doi: 10.3171/2009.9.JNS09577.
120. Yang, CF, Chiang, MC, Gray, DC, Prabhakaran, M, Alvarado, M, Juntti, SA, Unger, EK, Wells, JA, and Shah, NM. 2013. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153, 896-909. doi: 10.1016/j.cell.2013.04.017.
121. Yang, M, Augustsson, H, Markham, CM, Hubbard, DT, Webster, D, Wall, PM, Blanchard, RJ, and Blanchard, DC. 2004. The rat exposure test: a model of mouse defensive behaviors. Physiology & behavior 81, 465-473. doi: 10.1016/j.physbeh.2004.02.010 S003193840400054X [pii]
122. Yilmaz, M, and Meister, M (2013). Rapid Innate Defensive Responses of Mice to Looming Visual Stimuli. In Curr Biol (Elsevier Ltd), pp. 2011-2015.
123. Yizhar, O, Fenno, LE, Davidson, TJ, Mogri, M, and Deisseroth, K. 2011. Optogenetics in neural systems. Neuron 71, 9-34. doi: 10.1016/j.neuron.2011.06.004.