Ascending Control of Arousal and Motivation: Role of Nucleus Incertus and its Peptide Neuromodulators in Behavioural Responses to Stress

Journal of Neuroendocrinology

Volumn 27, Issue 6, 2015, Pages 457-467

  Ma, S ^a,b   Gundlach, A L ^a,b,c  

^a FLOREY INSTITUTE OF NEUROSCIENCE AND MENTAL HEALTH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Arousal; Corticotrophin releasing factor; Motivation; Nucleus incertus; Orexin; Oxytocin; Relaxin 3; Stress

Indexed keywords

CORTICOTROPIN RELEASING FACTOR; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; RELAXIN 3; SEROTONIN 1A RECEPTOR; STRESS HORMONE; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS;

AMYGDALOID NUCLEUS; AROUSAL; BEHAVIORAL STRESS; BRAIN REGION; COGNITION; CORTICOSTERONE BLOOD LEVEL; ELECTROENCEPHALOGRAM; EMOTION; GABAERGIC TRANSMISSION; HABENULA; HIPPOCAMPUS THETA RHYTHM; HYPOTHALAMUS; LOCOMOTION; MOTIVATION; NERVE CELL; NERVE CELL NETWORK; NONHUMAN; NUCLEUS INCERTUS; PREFRONTAL CORTEX; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; THALAMUS NUCLEUS; ADAPTATION; ANIMAL; HUMAN; PHYSIOLOGICAL STRESS; PHYSIOLOGY;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; AROUSAL; HUMANS; MOTIVATION; NEUROTRANSMITTER AGENTS; STRESS, PHYSIOLOGICAL;

EID: 84929731163     PISSN: 09538194     EISSN: 13652826     Source Type: Journal    
DOI: 10.1111/jne.12259     Document Type: Review

References (102)

1. Streeter GL. Anatomy of the floor of the fourth ventricle. Am J Anat 1903; 2: 299-313.
2. Ma S, Sang Q, Lanciego JL, Gundlach AL. Localization of relaxin-3 in brain of Macaca fascicularis: identification of a nucleus incertus in primate. J Comp Neurol 2009; 517: 856-872.
3. Ryan PJ, Ma S, Olucha-Bordonau FE, Gundlach AL. Nucleus incertus - an emerging modulatory role in arousal, stress and memory. Neurosci Biobehav Rev 2011; 35: 1326-1341.
4. Goto M, Swanson LW, Canteras NS. Connections of the nucleus incertus. J Comp Neurol 2001; 438: 86-122.
5. Olucha-Bordonau FE, Teruel V, Barcia-Gonzalez J, Ruiz-Torner A, Valverde-Navarro AA, Martinez-Soriano F. Cytoarchitecture and efferent projections of the nucleus incertus of the rat. J Comp Neurol 2003; 464: 62-97.
6. Smith CM, Shen P-J, Banerjee A, Bonaventure P, Ma S, Bathgate RAD, Sutton SW, Gundlach AL. Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain. J Comp Neurol 2010; 518: 4016-4045.
7. Hayakawa T, Zyo K. Comparative cytoarchitectonic study of Gudden's tegmental nuclei in some mammals. J Comp Neurol 1983; 216: 233-244.
8. Fuchs E, Wasmuth JC, Flugge G, Huether G, Troost R, Beyer J. Diurnal variation of corticotropin-releasing factor binding sites in the rat brain and pituitary. Cell Mol Neurobiol 1996; 16: 21-37.
9. Quina LA, Tempest L, Ng L, Harris JA, Ferguson S, Jhou TC, Turner EE. Efferent pathways of the mouse lateral habenula. J Comp Neurol 2015; 523: 32-60.
10. Jennes L, Stumpf WE, Kalivas PW. Neurotensin: topographical distribution in rat brain by immunohistochemistry. J Comp Neurol 1982; 210: 211-224.
11. Phillipson OT, Pycock CJ. Dopamine neurones of the ventral tegmentum project to both medial and lateral habenula. Some implications for habenular function. Exp Brain Res 1982; 45: 89-94.
12. Aizawa H, Kobayashi M, Tanaka S, Fukai T, Okamoto H. Molecular characterization of the subnuclei in rat habenula. J Comp Neurol 2012; 520: 4051-4066.
13. Kim U. Topographic commissural and descending projections of the habenula in the rat. J Comp Neurol 2009; 513: 173-187.
14. Aizawa H, Cui W, Tanaka K, Okamoto H. Hyperactivation of the habenula as a link between depression and sleep disturbance. Front Hum Neurosci 2013; 7: 826.
15. Sanchez-Perez AM, Arnal-Vicente I, Santos FN, Pereira CW, ElMlili N, Sanjuan J, Ma S, Gundlach AL, Olucha-Bordonau FE. Septal projections to the nucleus incertus in the rat: bidirectional pathways for modulation of hippocampal function. J Comp Neurol 2015; 523: 565-588.
16. Vertes RP, Kocsis B. Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 1997; 81: 893-926.
17. Goto M, Canteras NS, Burns G, Swanson LW. Projections from the subfornical region of the lateral hypothalamic area. J Comp Neurol 2005; 493: 412-438.
18. Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, Deisseroth K, Malenka RC. Input-specific control of reward and aversion in the ventral tegmental area. Nature 2012; 491: 212-217.
19. Olucha-Bordonau FE, Otero-Garcia M, Sanchez-Perez AM, Nunez A, Ma S, Gundlach AL. Distribution and targets of the relaxin-3 innervation of the septal area in the rat. J Comp Neurol 2012; 520: 1903-1939.
20. Allen Institute for Brain Science. Allen Brain Atlas [Internet]. Available from: http://www.brain-map.org.
21. Paxinos G, Franklin BJ. The Mouse Brain in Stereotaxic Coordinates. Boston, MA: Elsevier Academic Press, 2004.
22. Yoshida M, Takayanagi Y, Inoue K, Kimura T, Young LJ, Onaka T, Nishimori K. Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci 2009; 29: 2259-2271.
23. Taylor SR, Badurek S, Dileone RJ, Nashmi R, Minichiello L, Picciotto MR. GABAergic and glutamatergic efferents of the mouse ventral tegmental area. J Comp Neurol 2014; 522: 3308-3334.
24. Weissbourd B, Ren J, DeLoach KE, Guenthner CJ, Miyamichi K, Luo L. Presynaptic partners of dorsal raphe serotonergic and GABAergic neurons. Neuron 2014; 83: 645-662.
25. Ford B, Holmes CJ, Mainville L, Jones BE. GABAergic neurons in the rat pontomesencephalic tegmentum: codistribution with cholinergic and other tegmental neurons projecting to the posterior lateral hypothalamus. J Comp Neurol 1995; 363: 177-196.
26. Ma S, Bonaventure P, Ferraro T, Shen P-J, Burazin TCD, Bathgate RAD, Liu C, Tregear GW, Sutton SW, Gundlach AL. Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat. Neuroscience 2007; 144: 165-190.
27. Chronwall BM, Pisano JJ, Bishop JF, Moody TW, O'Donohue TL. Biochemical and histochemical characterization of ranatensin immunoreactive peptides in rat brain: lack of coexistence with bombesin/GRP. Brain Res 1985; 338: 97-113.
28. Moody TW, Korman LY, O'Donohue TL. Neuromedin B-like peptides in rat brain: biochemical characterization, mechanism of release and localization in synaptosomes. Peptides 1986; 7: 815-820.
29. Smith CM, Ryan PJ, Hosken IT, Ma S, Gundlach AL. Relaxin-3 systems in the brain - the first 10 years. J Chem Neuroanat 2011; 42: 262-275.
30. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf KR, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Yuan XF, Zhang B, Zwingman TA, Jones AR. Genome-wide atlas of gene expression in the adult mouse brain. Nature 2007; 445: 168-176.
31. Paxinos G, Carrive P, Wang H, Wang P-Y. Chemoarchitectonic Atlas of the Rat Brainstem. San Diego, CA: Academic Press, 1999.
32. Bathgate RAD, Samuel CS, Burazin TCD, Layfield S, Claasz AA, Reytomas IG, Dawson NF, Zhao C, Bond C, Summers RJ, Parry LJ, Wade JD, Tregear GW. Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family. J Biol Chem 2002; 277: 1148-1157.
33. Burazin TCD, Bathgate RAD, Macris M, Layfield S, Gundlach AL, Tregear GW. Restricted, but abundant, expression of the novel rat gene-3 (R3) relaxin in the dorsal tegmental region of brain. J Neurochem 2002; 82: 1553-1557.
34. Tanaka M, Iijima N, Miyamoto Y, Fukusumi S, Itoh Y, Ozawa H, Ibata Y. Neurons expressing relaxin 3/INSL 7 in the nucleus incertus respond to stress. Eur J Neurosci 2005; 21: 1659-1670.
35. Liu C, Eriste E, Sutton S, Chen J, Roland B, Kuei C, Farmer N, Jornvall H, Sillard R, Lovenberg TW. Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein coupled receptor GPCR135. J Biol Chem 2003; 278: 50754-50764.
36. Bathgate RAD, Ivell R, Sanborn BM, Sherwood OD, Summers RJ. International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. Pharmacol Rev 2006; 58: 7-31.
37. van der Westhuizen ET, Werry TD, Sexton PM, Summers RJ. The relaxin family peptide receptor 3 activates extracellular signal-regulated kinase 1/2 through a protein kinase C-dependent mechanism. Mol Pharmacol 2007; 71: 1618-1629.
38. Sutton SW, Bonaventure P, Kuei C, Roland B, Chen J, Nepomuceno D, Lovenberg TW, Liu C. Distribution of G-protein-coupled receptor (GPCR)135 binding sites and receptor mRNA in the rat brain suggests a role for relaxin-3 in neuroendocrine and sensory processing. Neuroendocrinology 2004; 80: 298-307.
39. Potter E, Sutton S, Donaldson C, Chen R, Perrin M, Lewis K, Sawchenko PE, Vale W. Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Proc Natl Acad Sci USA 1994; 91: 8777-8781.
40. Bittencourt JC, Sawchenko PE. Do centrally administered neuropeptides access cognate receptors? An analysis in the central corticotropin-releasing factor system. J Neurosci 2000; 20: 1142-1156.
41. Ma S, Blasiak A, Olucha-Bordonau FE, Verberne AJ, Gundlach AL. Heterogeneous responses of nucleus incertus neurons to corticotrophin-releasing factor and coherent activity with hippocampal theta rhythm in the rat. J Physiol 2013; 591: 3981-4001.
42. Justice NJ, Yuan ZF, Sawchenko PE, Vale W. Type 1 corticotropin-releasing factor receptor expression reported in BAC transgenic mice: implications for reconciling ligand-receptor mismatch in the central corticotropin-releasing factor system. J Comp Neurol 2008; 511: 479-496.
43. Potter E, Behan DP, Linton EA, Lowry PJ, Sawchenko PE, Vale WW. The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF. Proc Natl Acad Sci USA 1992; 89: 4192-4196.
44. Greco MA, Shiromani PJ. Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats. Brain Res Mol Brain Res 2001; 88: 176-182.
45. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M, Elmquist JK. Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol 2001; 435: 6-25.
46. Saito Y, Cheng M, Leslie FM, Civelli O. Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. J Comp Neurol 2001; 435: 26-40.
47. Wada E, Way J, Lebacq-Verheyden AM, Battey JF. Neuromedin B and gastrin-releasing peptide mRNAs are differentially distributed in the rat nervous system. J Neurosci 1990; 10: 2917-2930.
48. Merali Z, Graitson S, Mackay JC, Kent P. Stress and eating: a dual role for bombesin-like peptides. Front Neurosci 2013; 7: 193.
49. Boughton CK, Patel SA, Thompson EL, Patterson M, Curtis AE, Amin A, Chen K, Ghatei MA, Bloom SR, Murphy KG. Neuromedin B stimulates the hypothalamic-pituitary-gonadal axis in male rats. Regul Pept 2013; 187: 6-11.
50. Vaccari C, Lolait SJ, Ostrowski NL. Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain. Endocrinology 1998; 139: 5015-5033.
51. Mani BK, Walker AK, Lopez Soto EJ, Raingo J, Lee CE, Perello M, Andrews ZB, Zigman JM. Neuroanatomical characterization of a growth hormone secretagogue receptor-green fluorescent protein reporter mouse. J Comp Neurol 2014; 522: 3644-3666.
52. Miyamoto Y, Watanabe Y, Tanaka M. Developmental expression and serotonergic regulation of relaxin 3/INSL7 in the nucleus incertus of rat brain. Regul Pept 2008; 145: 54-59.
53. Banerjee A, Shen PJ, Ma S, Bathgate RAD, Gundlach AL. Swim stress excitation of nucleus incertus and rapid induction of relaxin-3 expression via CRF1 activation. Neuropharmacology 2010; 58: 145-155.
54. Huang Q, Timofeeva E, Richard D. Regulation of corticotropin-releasing factor and its types 1 and 2 receptors by leptin in rats subjected to treadmill running-induced stress. J Endocrinol 2006; 191: 179-188.
55. Kirby LG, Freeman-Daniels E, Lemos JC, Nunan JD, Lamy C, Akanwa A, Beck SG. Corticotropin-releasing factor increases GABA synaptic activity and induces inward current in 5-hydroxytryptamine dorsal raphe neurons. J Neurosci 2008; 28: 12927-12937.
56. Van Pett K, Viau V, Bittencourt JC, Chan RK, Li HY, Arias C, Prins GS, Perrin M, Vale W, Sawchenko PE. Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J Comp Neurol 2000; 428: 191-212.
57. Watanabe Y, Miyamoto Y, Matsuda T, Tanaka M. Relaxin-3/INSL7 regulates the stress-response system in the rat hypothalamus. J Mol Neurosci 2010; 43: 169-174.
58. McGowan BM, Minnion JS, Murphy KG, Roy D, Stanley SA, Dhillo WS, Gardiner JV, Ghatei MA, Bloom SR. Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing hormone. J Endocrinol 2014; 221: 337-346.
59. Ribeiro-Barbosa ER, Canteras NS, Cezario AF, Blanchard RJ, Blanchard DC. An alternative experimental procedure for studying predator-related defensive responses. Neurosci Biobehav Rev 2005; 29: 1255-1263.
60. Cullinan WE, Herman JP, Battaglia DF, Akil H, Watson SJ. Pattern and time course of immediate early gene expression in rat brain following acute stress. Neuroscience 1995; 64: 477-505.
61. Senba E, Matsunaga K, Tohyama M, Noguchi K. Stress-induced c-fos expression in the rat brain: activation mechanism of sympathetic pathway. Brain Res Bull 1993; 31: 329-344.
62. Lee LC, Rajkumar R, Dawe GS. Selective lesioning of nucleus incertus with corticotropin releasing factor-saporin conjugate. Brain Res 2014; 1543: 179-190.
63. Pereira CW, Santos FN, Sanchez-Perez AM, Otero-Garcia M, Marchioro M, Ma S, Gundlach AL, Olucha-Bordonau FE. Electrolytic lesion of the nucleus incertus retards extinction of auditory conditioned fear. Behav Brain Res 2013; 247: 201-210.
64. Quirk GJ, Mueller D. Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 2008; 33: 56-72.
65. Lenglos C, Mitra A, Guevremont G, Timofeeva E. Sex differences in the effects of chronic stress and food restriction on body weight gain and brain expression of CRF and relaxin-3 in rats. Genes Brain Behav 2013; 12: 370-387.
66. Lenglos C, Mitra A, Guevremont G, Timofeeva E. Regulation of expression of relaxin-3 and its receptor RXFP3 in the brain of diet-induced obese rats. Neuropeptides 2014; 48: 119-132.
67. McGowan BM, Stanley SA, Smith KL, White NE, Connolly MM, Thompson EL, Gardiner JV, Murphy KG, Ghatei MA, Bloom SR. Central relaxin-3 administration causes hyperphagia in male Wistar rats. Endocrinology 2005; 146: 3295-3300.
68. Shabanpoor F, Akhter Hossain M, Ryan PJ, Belgi A, Layfield S, Kocan M, Zhang S, Samuel CS, Gundlach AL, Bathgate RA, Separovic F, Wade JD. Minimization of human relaxin-3 leading to high-affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1. J Med Chem 2012; 55: 1671-1681.
69. Haugaard-Kedstrom LM, Shabanpoor F, Hossain MA, Clark RJ, Ryan PJ, Craik DJ, Gundlach AL, Wade JD, Bathgate RA, Rosengren KJ. Design, synthesis, and characterization of a single-chain peptide antagonist for the relaxin-3 receptor RXFP3. J Am Chem Soc 2011; 133: 4965-4974.
70. Kuei C, Sutton S, Bonaventure P, Pudiak C, Shelton J, Zhu J, Nepomuceno D, Wu J, Chen J, Kamme F, Seierstad M, Hack MD, Bathgate RA, Hossain MA, Wade JD, Atack J, Lovenberg TW, Liu C. R3(BDelta23 27)R/I5 chimeric peptide, a selective antagonist for GPCR135 and GPCR142 over relaxin receptor LGR7: in vitro and in vivo characterization. J Biol Chem 2007; 282: 25425-25435.
71. Ganella DE, Callander GE, Ma S, Bye CR, Gundlach AL, Bathgate RA. Modulation of feeding by chronic rAAV expression of a relaxin-3 peptide agonist in rat hypothalamus. Gene Ther 2013; 20: 703-716.
72. Smith CM, Chua BE, Zhang C, Walker AW, Haidar M, Hawkes D, Shabanpoor F, Hossain MA, Wade JD, Rosengren KJ, Gundlach AL. Central injection of relaxin-3 receptor (RXFP3) antagonist peptides reduces motivated food seeking and consumption in C57BL/6J mice. Behav Brain Res 2014; 268: 117-126.
73. Ryan PJ, Kastman HE, Krstew EV, Rosengren KJ, Hossain MA, Churilov L, Wade JD, Gundlach AL, Lawrence AJ. Relaxin-3/RXFP3 system regulates alcohol-seeking. Proc Natl Acad Sci USA 2013; 110: 20789-20794.
74. Ehlers CL, Chaplin RI, Wall TL, Lumeng L, Li TK, Owens MJ, Nemeroff CB. Corticotropin releasing factor (CRF): studies in alcohol preferring and non-preferring rats. Psychopharmacology 1992; 106: 359-364.
75. Ryan PJ, Krstew EV, Sarwar M, Gundlach AL, Lawrence AJ. Relaxin-3 mRNA levels in nucleus incertus correlate with alcohol and sucrose intake in rats. Drug Alcohol Depend 2014; 140: 8-16.
76. Betley JN, Sternson SM. Adeno-associated viral vectors for mapping, monitoring, and manipulating neural circuits. Hum Gene Ther 2011; 22: 669-677.
77. Urban DJ, Roth BL. DREADDs (Designer Receptors Exclusively Activated by Designer Drugs): chemogenetic tools with therapeutic utility. Annu Rev Pharmacol Toxicol 2015; 55: 399-417.
78. Ma S. Nucleus incertus and relaxin-3: An emerging modulatory role in arousal, stress and memory in The 8th International Congress of Neuroendocrinology. Sydney, Australia: 2014: 5.
79. Buzsaki G, Logothetis N, Singer W. Scaling brain size, keeping timing: evolutionary preservation of brain rhythms. Neuron 2013; 80: 751-764.
80. Vertes RP. Brainstem control of the events of REM sleep. Prog Neurobiol 1984; 22: 241-288.
81. Vertes RP. Hippocampal theta rhythm: a tag for short-term memory. Hippocampus 2005; 15: 923-935.
82. McNaughton N, Gray JA. Anxiolytic action on the behavioural inhibition system implies multiple types of arousal contribute to anxiety. J Affect Disord 2000; 61: 161-176.
83. Stujenske JM, Likhtik E, Topiwala MA, Gordon JA. Fear and safety engage competing patterns of theta-gamma coupling in the basolateral amygdala. Neuron 2014; 83: 919-933.
84. Simon AP, Poindessous-Jazat F, Dutar P, Epelbaum J, Bassant MH. Firing properties of anatomically identified neurons in the medial septum of anesthetized and unanesthetized restrained rats. J Neurosci 2006; 26: 9038-9046.
85. Hangya B, Borhegyi Z, Szilagyi N, Freund TF, Varga V. GABAergic neurons of the medial septum lead the hippocampal network during theta activity. J Neurosci 2009; 29: 8094-8102.
86. Nunez A, Cervera-Ferri A, Olucha-Bordonau F, Ruiz-Torner A, Teruel V. Nucleus incertus contribution to hippocampal theta rhythm generation. Eur J Neurosci 2006; 23: 2731-2738.
87. Vertes RP, Martin GF. Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat. J Comp Neurol 1988; 275: 511-541.
88. Teruel-Marti V, Cervera-Ferri A, Nunez A, Valverde-Navarro AA, Olucha-Bordonau FE, Ruiz-Torner A. Anatomical evidence for a ponto-septal pathway via the nucleus incertus in the rat. Brain Res 2008; 1218: 87-96.
89. Ma S, Olucha-Bordonau FE, Hossain MA, Lin F, Kuei C, Liu C, Wade JD, Sutton SW, Nunez A, Gundlach AL. Modulation of hippocampal theta oscillations and spatial memory by relaxin-3 neurons of the nucleus incertus. Learn Mem 2009; 16: 730-742.
90. Guzman YF, Tronson NC, Jovasevic V, Sato K, Guedea AL, Mizukami H, Nishimori K, Radulovic J. Fear-enhancing effects of septal oxytocin receptors. Nat Neurosci 2013; 16: 1185-1187.
91. Mitra A, Lenglos C, Timofeeva E. Inhibition in the lateral septum increases sucrose intake and decreases anorectic effects of stress. Eur J Neurosci 2014; Nov 24. doi: 10.1111/ejn.12798. [Epub ahead of print].
92. Cervera-Ferri A, Guerrero-Martinez J, Bataller-Mompean M, Taberner-Cortes A, Martinez-Ricos J, Ruiz-Torner A, Teruel-Marti V. Theta synchronization between the hippocampus and the nucleus incertus in urethane-anesthetized rats. Exp Brain Res 2011; 211: 177-192.
93. Tsukahara S, Kanaya M, Yamanouchi K. Neuroanatomy and sex differences of the lordosis-inhibiting system in the lateral septum. Front Neurosci 2014; 8: 299.
94. Chee SS, Menard JL, Dringenberg HC. Behavioral anxiolysis without reduction of hippocampal theta frequency after histamine application in the lateral septum of rats. Hippocampus 2014; 24: 615-627.
95. Allsop SA, Vander Weele CM, Wichmann R, Tye KM. Optogenetic insights on the relationship between anxiety-related behaviors and social deficits. Front Behav Neurosci 2014; 8: 241.
96. Nakajima M, Gorlich A, Heintz N. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons. Cell 2014; 159: 295-305.
97. Tanaka M. Relaxin-3/insulin-like peptide 7, a neuropeptide involved in the stress response and food intake. FEBS J 2010; 277: 4990-4997.
98. Smith CM, Walker AW, Hosken IT, Chua BE, Zhang C, Haidar M, Gundlach AL. Relaxin-3/RXFP3 networks: an emerging target for the treatment of depression and other neuropsychiatric diseases? Front Pharmacol 2014; 5: 46.
99. Atasoy D, Betley JN, Li WP, Su HH, Sertel SM, Scheffer LK, Simpson JH, Fetter RD, Sternson SM. A genetically specified connectomics approach applied to long-range feeding regulatory circuits. Nat Neurosci 2014; 17: 1830-1839.
100. Sasaki K, Suzuki M, Mieda M, Tsujino N, Roth B, Sakurai T. Pharmacogenetic modulation of orexin neurons alters sleep/wakefulness states in mice. PLoS ONE 2011; 6: e20360.
101. Ting JT, Feng G. Recombineering strategies for developing next generation BAC transgenic tools for optogenetics and beyond. Front Behav Neurosci 2014; 8: 111.
102. Steinberg EE, Christoffel DJ, Deisseroth K, Malenka RC. Illuminating circuitry relevant to psychiatric disorders with optogenetics. Curr Opin Neurobiol 2014; 30: 9-16.