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The Lateral Habenula: No Longer Neglected

Published online by Cambridge University Press:  07 November 2014

Stefanie Geisler  and
Michael Trimble
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Extract

In this contribution to the CNS Spectrums neuroanatomy series, Stefanie Geisler, MD, discusses the lateral habenula (LHb). This nuclear complex is one of the areas of the brain that forms part of the cross-talk between limbic fore-brain and some important ascending modulatory pathways. Situated at the caudal end of the dorsal diencephalon and classically regarded as projecting largely to the brainstem, including the serotoninergic raphe nuclei, the LHb receives afferents from widespread forebrain areas. Therefore, the LHb is able to influence serotonin tone in the brain, and has long interested neuroanatomists as a potential limbic-motor interface. Nonetheless, the LHb was not much discussed outside neuroanatomical circles until recently, when it was discovered that its impact on the mesotelencephalic dopamine system is probably much greater than had been assumed. The LHb has become a hot topic. This article-addresses these developments and emphasizes the clinical relevance of this interesting brain structure.

Type
Brain Regions of Interest
Information
CNS Spectrums , Volume 13 , Issue 6 , June 2008 , pp. 484 - 489
Copyright
Copyright © Cambridge University Press 2008

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References

REFERENCES

1.Morgan, MJ, O'Donnell, JM, Oliver, RF. Development of left-right asymmetry in the habenular nuclei of Rana temporaria. J Comp Neurol. 1973;149:203–214.CrossRefGoogle ScholarPubMed
2.Cajal, SR. The habenula. In: Histology of the Nervous System, vol 2. New York, NY: Oxford University Press: 1995:342–350.Google Scholar
3.Meyer, G, Ferres-Torres, R. The dendritic structure of the habenula in the albino mouse [German]. J Hirnforsch. 1981;22:153–159.Google Scholar
4.Herkenham, M, Nauta, WJ. Efferent connections of the habenular nuclei in the rat. J Comp Neurol. 1979;187:19–47.CrossRefGoogle ScholarPubMed
5.Herkenham, M, Nauta, WJ. Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber-of-passage problem. J Comp Neurol. 1977;173:123–146.CrossRefGoogle Scholar
6.Iwahori, N. A Golgi study on the habenular nucleus of the cat. J Comp Neurol. 1977;72:319–344.CrossRefGoogle Scholar
7.Andres, KH, von During, M, Veh, RW. Subnuclear organization of the rat habenular complexes. J Comp Neurol. 1999;407:130–150.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
8.Geisler, S, Andres, KH, Veh, RW. Morphologic and cytochemical criteria for the identification and delineation of individual subnuclei within the lateral habenular complex of the rat. J Comp Neurol. 2003;458:78–97.Google Scholar
9.Chastrette, N, Pfaff, DW, Gibbs, RB. Effects of daytime and nighttime stress on Fos-like immunoreactivity in the paraventricular nucleus of the hypothalamus, the habenula, and the posterior paraventricular nucleus of the thalamus. Brain Res. 1991;563:339–344.Google Scholar
10.Wirtshafter, D, Asin, KE, Pitzer, MR. Dopamine agonists and stress produce different patterns of Fos-like immunoreactivity in the lateral habenula. Brain Res. 1994;633:21–26.CrossRefGoogle ScholarPubMed
11.Timofeeva, E, Richard, D. Activation of the central nervous system in obese Zucker rats during food deprivation. J Comp Neurol. 2001;441:71–89.CrossRefGoogle ScholarPubMed
12.Amat, J, Sparks, PD, Matus-Amat, P, Griggs, J, Watkins, LR, Maier, SF. The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress. Brain Res. 2001;917:118–126.CrossRefGoogle ScholarPubMed
13.Villarreal, JS, Gonzalez-Lima, F, Berndt, J, Barea-Rodriguez, EJ. Water maze training in aged rats: effects on brain metabolic capacity and behavior. Brain Res. 2002;939:43–51.CrossRefGoogle ScholarPubMed
14.Corodimas, KP, Rosenblatt, JS, Canfield, ME, Morrell, JI. Neurons in the lateral subdivision of the habenular complex mediate the hormonal onset of maternal behavior in rats. Behav Neurosci. 1993;107:827–843.Google Scholar
15.Corodimas, KP, Rosenblatt, JS, Morrell, JI. The habenular complex mediates hormonal stimulation of maternal behavior in rats. Behav Neurosci. 1992;106:853–865.CrossRefGoogle ScholarPubMed
16.Felton, TM, Linton, L, Rosenblatt, JS, Morrell, JI. Intact neurons of the lateral habenular nucleus are necessary for the nonhormonal, pup-mediated display of maternal behavior in sensitized virgin female rats. Behav Neurosci. 1998;112:1458–1465.Google Scholar
17.Kalinichev, M, Rosenblatt, JS, Nakabeppu, Y, Morrell, JI. Induction of c-fos-like and fosB-like immunoreactivity reveals forebrain neuronal populations involved differentially in pup-mediated maternal behavior in juvenile and adult rats. J Comp Neurol. 2000;416:45–78.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
18.Nagao, M, Kamo, H, Akiguchi, I, Kimura, J. Induction of c-Fos-like protein in the lateral habenular nucleus by persistent noxious peripheral stimulation. Neurosci Lett. 1993;151:37–40.CrossRefGoogle ScholarPubMed
19.Cohen, SR, Melzack, R. Habenular stimulation produces analgesia in the formalin test. Neurosci Lett. 1986;70:165–169.Google Scholar
20.Cohen, SR, Melzack, R. The habenula and pain: repeated electrical stimulation produces prolonged analgesia but lesions have no effect on formalin pain or morphine analgesia. Behav Brain Res. 1993;54:171–178.Google Scholar
21.Cohen, SR, Melzack, R. Morphine injected into the habenula and dorsal posteromedial thalamus produces analgesia in the formalin test. Brain Res. 1985;359:131–139.Google Scholar
22.Terenzi, MG, Guimaraes, FS, Prado, WA. Antinociception induced by stimulation of the habenular complex of the rat. Brain Res. 1990;524:213–218.Google Scholar
23.Guilding, C, Piggins, HD. Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain? Eur J Neurosci. 2007;25:3195–3216.CrossRefGoogle ScholarPubMed
24.Tavakoli-Nezhad, M, Schwartz, WJ. c-Fos expression in the brains of behaviorally “split” hamsters in constant light: calling attention to a dorsolateral region of the suprachiasmatic nucleus and the medial division of the lateral habenula. J Biol Rhythms. 2005;20:419–429.Google Scholar
25.Zhao, H, Rusak, B. Circadian firing-rate rhythms and light responses of rat habenular nucleus neurons in vivo and in vitro. Neuroscience. 2005;132:519–528.CrossRefGoogle ScholarPubMed
26.Hattar, S, Kumar, M, Park, A, et, al. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol. 2006;497:326–349.Google Scholar
27.Qu, T, Dong, K, Sugioka, K, Yamadori, T. Demonstration of direct input from the retina to the lateral habenular nucleus in the albino rat. Brain Res. 1996;709:251–258.Google Scholar
28.Lecourtier, L, Kelly, PH. A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition. Neurosci Biobehav Rev. 2007;31:658–672.CrossRefGoogle ScholarPubMed
29.Sutherland, RJ, Nakajima, S. Self-stimulation of the habenular complex in the rat. J Comp Physiol Psychol. 1981;95:781–791.Google Scholar
30.Morissette, MC, Boye, SM. Electrolytic lesions of the habenula attenuate brain stimulation reward. Behav Brain Res. 2008;187:17–26.CrossRefGoogle ScholarPubMed
31.Vachon, MP, Miliaressis, E. Dorsal diencephalic self-stimulation: a movable electrode mapping study. Behav Neurosci. 1992;106:981–991.CrossRefGoogle ScholarPubMed
32.Nakajima, S. Serotonergic mediation of habenular self-stimulation in the rat. Pharmacol Biochem Behav. 1984;20:859–862.CrossRefGoogle ScholarPubMed
33.Ullsperger, M, von Cramon, DY. Error monitoring using external feedback: specific roles of the habenular complex, the reward system, and the cingulate motor area revealed by functional magnetic resonance imaging. J Neurosci. 2003;23:4308–4314.Google Scholar
34.Matsumoto, M, Hikosaka, O. Lateral habenula as a source of negative reward signals in dopamine neurons. Nature. 2007;447:1111–1115.Google Scholar
35.Paxinos, G, Watson, C. The Rat Brain in Stereotaxic Coordinates. 4thed. San Diego, Calif: Academe Press; 1998.Google Scholar
36.Sutherland, RJ. The dorsal diencephalic conduction system: a review of the anatomy and functions of the habenular complex. Neurosci Biobehav Rev. 1982;6:1–13.Google Scholar
37.Ellison, G. Stimulant-induced psychosis, the dopamine theory of schizophrenia, and the habenula. Brain Res Brain Res Rev. 1994;19:223–239.Google Scholar
38.Kelly, PH. Defective inhibition of dream event memory formation: a hypothesized mechanism in the onset and progression of symptoms of schizophrenia. Brain Res Bull. 1998;46:189–197.Google Scholar
39.Lecourtier, L, Neijt, HC, Kelly, PH. Habenula lesions cause impaired cognitive performance in rats: implications for schizophrenia. Eur J Neurosci. 2004;19:2551–2560.Google Scholar
40.Shepard, PD, Holcomb, HH, Gold, JM. Schizophrenia in translation: the presence of absence: habenular regulation of dopamine neurons and the encoding of negative outcomes. Schizophr Bull. 2006;32:417–421.CrossRefGoogle ScholarPubMed
41.Morris, JS, Smith, KA, Cowen, PJ, Friston, KJ, Dolan, RJ. Covariation of activity in habenula and dorsal raphe nuclei following tryptophan depletion. Neuroimage. 1999;10:163–172.Google Scholar
42.Nauta, WJ. Hippocampal projections and related neural pathways to the midbrain in the cat. Brain. 1958;81:319–340.Google Scholar
43.Kowski, AB, Geisler, S, Krauss, M, Veh, RW. Differential projections from subfields in the lateral preoptic area to the lateral habenular complex of the rat. J Comp Neurol. 2008;507:1465–1478.Google Scholar
44.Groenewegen, HJ, Berendse, HW, Haber, SN. Organization of the output of the ventral striatopallidal system in the rat: ventral pallidal efferents. Neuroscience. 1993;57:113–142.CrossRefGoogle ScholarPubMed
45.Zahm, DS, Williams, E, Wohltmann, C. Ventral striatopallidothalamic projection: IV. Relative involvements of neurochemically distinct subterritories in the ventral pallidum and adjacent parts of the rostroventral forebrain. J Comp Neurol. 1996;364:340–362.3.0.CO;2-T>CrossRefGoogle ScholarPubMed
46.Rajakumar, N, Elisevich, K, Flumerfelt, BA. Compartmental origin of the striato-entopeduncular projection in the rat. J Comp Neurol. 1993;331:286–296.CrossRefGoogle ScholarPubMed
47.Parent, A, Gravel, S, Boucher, R. The origin of forebrain afferents to the habenula in rat, cat and monkey. Brain Res Bull. 1981;6:23–38.Google Scholar
48.Haber, SN, Lynd-Balta, E, Mitchell, SJ. The organization of the descending ventral pallidal projections in the monkey. J Comp Neurol. 1993;329:111–128.CrossRefGoogle ScholarPubMed
49.Alexander, GE, Crutcher, MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990;13:266–271.Google Scholar
50.Alexander, GE, Crutcher, MD, DeLong, MR. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions. Prog Brain Res. 1990;85:119–146.CrossRefGoogle ScholarPubMed
51.Parent, M, Levesque, M, Parent, A. Two types of projection neurons in the internal pallidum of primates: single-axon tracing and three-dimensional reconstruction. J Comp Neurol. 2001;439:162–175.Google Scholar
52.Sidibe, M, Bevan, MD, Bolam, JP, Smith, Y. Efferent connections of the internal globus pallidus in the squirrel monkey: I. Topography and synaptic organization of the pallidothalamic projection. J Comp Neurol. 1997;382:323–347.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
53.Bevan, MD, Clarke, NP, Bolam, JP. Synaptic integration of functionally diverse pallidal information in the entopeduncular nucleus and subthalamic nucleus in the rat. J Neurosci. 1997;17:308–324.CrossRefGoogle ScholarPubMed
54.Zahm, DS. Functional-anatomical implications of the nucleus accumbens core and shell subterritories. Ann N Y Acad Sci. 1999;877:113–128.Google Scholar
55.Groenewegen, HJ, Trimble, M. The ventral striatum as an interface between the limbic and motor systems. CNS Spectr. 2007;12:887–892.Google Scholar
56.Li, YQ, Takada, M, Shinonaga, Y, Mizuno, N. The sites of origin of dopaminergic afferent fibers to the lateral habenular nucleus in the rat. J Comp Neurol. 1993;333:118–133.Google Scholar
57.Chiba, T, Kayahara, T, Nakano, K. Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata. Brain Res. 2001;888:83–101.Google Scholar
58.Kanemaru, H, Nakamura, H, Isayama, H, Kawabuchi, M, Tashiro, N. Efferent connections of the anterior hypothalamic nucleus: a biocytin study in the cat. Brain Res Bull. 2000;51:219–232.Google Scholar
59.Beckstead, RM. An autoradiographic examination of corticocortical and subcortical projections of the mediodorsal-projection (prefrontal) cortex in the rat. J Comp Neurol. 1979;184:43–62.Google Scholar
60.Cornwall, J, Cooper, JD, Phillipson, OT. Afferent and efferent connections of the laterodorsal tegmental nucleus in the rat. Brain Res Bull. 1990;25:271–284.CrossRefGoogle ScholarPubMed
61.Del-Fava, F, Hasue, RH, Ferreira, JG, Shammah-Lagnado, SJ. Efferent connections of the rostral linear nucleus of the ventral tegmental area in the rat. Neuroscience. 2007;145:1059–1076.Google Scholar
62.Skagerberg, G, Lindvall, O, Bjorklund, A. Origin, course and termination of the mesohabenular dopamine pathway in the rat. Brain Res. 1984;307:99–108.Google Scholar
63.Gruber, C, Kahl, A, Lebenheim, L, Kowski, A, Dittgen, A, Veh, RW. Dopaminergic projections from the VTA substantially contribute to the mesohabenular pathway in the rat. Neurosci Lett. 2007;427:165–170.CrossRefGoogle Scholar
64.Kalen, P, Karlson, M, Wiklund, L. Possible excitatory amino acid afferents to nucleus raphe dorsalis of the rat investigated with retrograde wheat germ agglutinin and D-[3H]aspartate tracing. Brain Res. 1985;360:285–297.Google Scholar
65.Semba, K, Fibiger, HC. Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: a retro- and antero-grade transport and immunohistochemical study. J Comp Neurol. 1992;323:387–410.Google Scholar
66.Araki, M, McGeer, PL, Kimura, H. The efferent projections of the rat lateral habenular nucleus revealed by the PHA-L anterograde tracing method. Brain Res. 1988;441:319–330.CrossRefGoogle ScholarPubMed
67.Behzadi, G, Kalen, P, Parvopassu, F, Wiklund, L. Afferents to the median raphe nucleus of the rat: retrograde cholera toxin and wheat germ conjugated horseradish peroxidase tracing, and selective D-[3H]aspartate labelling of possible excitatory amino acid inputs. Neuroscience. 1990;37:77–100.CrossRefGoogle Scholar
68.Mesulam, MM. Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Ann Neurol. 1990;28:597–613.Google Scholar
69.Geisler, S, Marinelli, M, Degarmo, B, et, al. Prominent activation of brainstem and pallidal afferents of the ventral tegmental area by cocaine. Neuropsychopharmacology. 2007;Dec 19 [Epub ahead of print].Google Scholar
70.Perrotti, LI, Bolanos, CA, Choi, KH, et, al. DeltaFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment. Eur J Neurosci. 2005;21:2817–2824.Google Scholar
71.Jhou, TC, Gallagher, M. Paramedian raphe neurons that project to midbrain dopamine neurons are activated by aversive stimuli. Soc Neurosci Abstr. 2007:Program #425.5.Google Scholar
72.Scammell, TE, Estabrooke, IV, McCarthy, MT, et al.Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci. 2000;20:8620–8628.Google Scholar
73.Zahm, DS, Trimble, M. The dopaminergic projection system, basal forebrain macrosystems, and conditioned stimuli. CNS Spectr. 2008;13:32–40.Google Scholar
74.Alheid, GF, Heimer, L. New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience. 1988;27:1–39.Google Scholar
75.Zahm, DS. The evolving theory of basal forebrain functional-anatomical ‘macrosystems’. Neurosci Biobehav Rev. 2006;30:148–172.Google Scholar
76.Alheid, GF, Heimer, L. Theories of basal forebrain organization and the “emotional motor system”. Prog Brain Res. 1996;107:461–484.Google Scholar
77.Heimer, L, Van Hoesen, GW. The limbic lobe and its output channels: implications for emotional functions and adaptive behavior. Neurosci Biobehav Rev. 2006;30:126–147.CrossRefGoogle ScholarPubMed
78.Heimer, L, de Olmos, J, Alheid, GF, Zaborszky, L. “Perestroika” in the basal forebrain: opening the border between neurology and psychiatry. Prog Brain Res. 1991;87:109–165.Google Scholar
79.Christoph, GR, Leonzio, RJ, Wilcox, KS. Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmental area of the rat. J Neurosci. 1986;6:613–619.Google Scholar
80.Ji, H, Shepard, PD. Lateral habenula stimulation inhibits rat midbrain dopamine neurons through a GABA(A) receptor-mediated mechanism. J Neurosci. 2007;27:6923–6930.Google Scholar
81.Schultz, W. Predictive reward signal of dopamine neurons. J Neurophysiol. 1998;80:1–27.Google Scholar
82.Thornton, EW, Evans, JA, Harris, C. Attenuated response to nomifensine in rats during a swim test following lesion of the habenula complex. Psychopharmacology (Berl). 1985;87:81–85.Google Scholar
83.Caldecott-Hazard, S, Mazziotta, J, Phelps, M. Cerebral correlates of depressed behavior in rats, visualized using 14C-2-deoxyglucose autoradiography. J Neurosci. 1988;8:1951–1961.Google Scholar
84.Shumake, J, Conejo-Jimenez, N, Gonzalez-Pardo, H, Gonzalez-Lima, F. Brain differences in newborn rats predisposed to helpless and depressive behavior. Brain Res. 2004;1030:267–276.Google Scholar
85.Shumake, J, Edwards, E, Gonzalez-Lima, F. Opposite metabolic changes in the habenula and ventral tegmental area of a genetic model of helpless behavior. Brain Res. 2003;963:274–281.CrossRefGoogle ScholarPubMed
86.Yang, LM, Hu, B, Xia, YH, Zhang, BL, Zhao, H. Lateral habenula lesions improve the behavioral response in depressed rats via increasing the serotonin level in dorsal raphe nucleus. Behav Brain Res. 2008;188:84–90.Google Scholar
87.Stern, WC, Johnson, A, Bronzino, JD, Morgane, PJ. Effects of electrical stimulation of the lateral habenula on single-unit activity of raphe neurons. Exp Neurol. 1979;65:326–342.Google Scholar
88.Aghajanian, GK, Wang, RY. Habenular and other midbrain raphe afferents demonstrated bya modified retrograde tracing technique. Brain Res. 1977;122:229–242.Google Scholar
89.Wang, RY, Aghajanian, GK. Physiological evidence for habenula as major link between forebrain and midbrain raphe. Science. 1977;197:89–91.Google Scholar
90.Nishikawa, T, Scatton, B. Inhibitory influence of GABA on central serotonergic transmission. Involvement of the habenulo-raphé pathways in the GABAergic inhibition of ascending cerebral serotonergic neurons. Brain Res. 1985;331:81–90.Google Scholar
91.Ferraro, G, Montalbano, ME, Sardo, P, La Grutta, V. Lateral habenular influence on dorsal raphe neurons. Brain Res Bull. 1996;41:47–52.Google Scholar
92.Varga, V, Kocsis, B, Sharp, T. Electrophysiological evidence for convergence of inputs from the medial prefrontal cortex and lateral habenula on single neurons in the dorsal raphe nucleus. Eur J Neurosci. 2003;17:280–286.Google Scholar