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In [[neuroanatomy]], '''habenula''' (diminutive of Latin ''habena'' meaning [[rein]]) originally denoted the stalk of the [[pineal gland]] (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the pineal gland was believed to be associated, the habenular nucleus. The habenular nucleus is a set of well-conserved structures in all [[vertebrate]] animals.<ref name="Andres">Andres, KH; During MV, Veh RW (1999). "Subnuclear organization of the rat habenular complexes.". Journal of Comparative Neurology 407 (1): 130–150. {{doi|10.1002/(SICI)1096-9861(19990428)407:1<130::AID-CNE10>3.0.CO;2-8}}. PMID 10213193</ref>
In [[neuroanatomy]], '''habenula''' (diminutive of Latin ''habena'' meaning [[rein]]) originally denoted the stalk of the [[pineal gland]] (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the pineal gland was believed to be associated, the habenular nucleus. The habenular nucleus is a set of well-conserved structures in all [[vertebrate]] animals.<ref name="Andres">Andres, KH; During MV, Veh RW (1999). "Subnuclear organization of the rat habenular complexes." ''Journal of Comparative Neurology'' 407 (1): 130–150. {{doi|10.1002/(SICI)1096-9861(19990428)407:1<130::AID-CNE10>3.0.CO;2-8}} PMID 10213193</ref>


Currently, the [[Terminologia Anatomica]] term refers exclusively to this separate cell mass in the caudal and dorsal aspect of the dorsal [[thalamus]] (the [[epithalamus]]), embedded in the [[Posterior (anatomy)|posterior]] end of the [[Stria medullaris|medullary stria]] from which it receives most of its [[Afferent nerve|afferent]] fibers. By way of the [[fasciculus retroflexus]] (habenulointerpeduncular tract) it projects to the [[interpeduncular nucleus]] and other paramedian cell groups of the [[midbrain tegmentum]].
Currently, the [[Terminologia Anatomica]] term refers exclusively to this separate cell mass in the caudal and dorsal aspect of the dorsal [[thalamus]] (the [[epithalamus]]), embedded in the [[Posterior (anatomy)|posterior]] end of the [[Stria medullaris|medullary stria]] from which it receives most of its [[Afferent nerve|afferent]] fibers. By way of the [[fasciculus retroflexus]] (habenulointerpeduncular tract) it projects to the [[interpeduncular nucleus]] and other paramedian cell groups of the [[midbrain tegmentum]].
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Neurons in the lateral habenula are ‘reward-negative’ as they are activated by stimulus associated with unpleasant events, the absence of the reward or punishment especially when this is unpredictable.<ref>Matsumoto M, Hikosaka O. (2009). Representation of negative motivational value in the primate lateral habenula. Nat Neurosci. 12(1):77-84. PMID 19043410</ref> Reward information to the lateral habenula comes from the internal part of the globus pallidus.<ref>Hong S, Hikosaka O. (2008). The globus pallidus sends reward-related signals to the lateral habenula. Neuron. 60(4):720-9. PMID 19038227</ref>
Neurons in the lateral habenula are ‘reward-negative’ as they are activated by stimulus associated with unpleasant events, the absence of the reward or punishment especially when this is unpredictable.<ref>Matsumoto M, Hikosaka O. (2009). Representation of negative motivational value in the primate lateral habenula. Nat Neurosci. 12(1):77-84. PMID 19043410</ref> Reward information to the lateral habenula comes from the internal part of the globus pallidus.<ref>Hong S, Hikosaka O. (2008). The globus pallidus sends reward-related signals to the lateral habenula. Neuron. 60(4):720-9. PMID 19038227</ref>


The outputs of the lateral habenula target dopaminergic regions ([[substantia nigra]] [[pars compacta]] and the [[ventral tegmental area]]), serotonergic regions ([[Median raphe nucleus|median raphe]] and [[dorsal raphe nucleus|dorsal raphe nuclei]]), and a cholinergic region (the [[laterodorsal tegmental nucleus]]).<ref name="Geisler" /> This output inhibits dopamine neurons in substantia nigra pars compacta and the ventral tegmental area, with activation in the lateral habenula linking to deactivation in them, and vice versa, deactivation in the lateral habenula with their activation.<ref>Matsumoto M, Hikosaka O. (2007). Lateral habenula as a source of negative reward signals in dopamine neurons. Nature. 447(7148):1111-5. PMID 17522629</ref> The lateral habenula functions to oppose the action of the laterodorsal tegmental nucleus in the acquisition of [[avoidance response]]s but not the processing of avoidance later on when it is a memory, motivation or its execution.<ref>Shumake J, Ilango A, Scheich H, Wetzel W, Ohl FW, (2010). Differential Neuromodulation of Acquisition and Retrieval of Avoidance Learning by the Lateral Habenula and Ventral Tegmental Area. Journal of Neuroscience, 30(17):5876–5883 {{DOI|10.1523/JNEUROSCI.3604-09.2010}}</ref> New research suggests that lateral habenula may play a crucial role in decision making.<ref>http://www.sciencedaily.com/releases/2013/11/131124200554.htm</ref>
The outputs of the lateral habenula target dopaminergic regions ([[substantia nigra]] [[pars compacta]] and the [[ventral tegmental area]]), serotonergic regions ([[Median raphe nucleus|median raphe]] and [[dorsal raphe nucleus|dorsal raphe nuclei]]), and a cholinergic region (the [[laterodorsal tegmental nucleus]]).<ref name="Geisler" /> This output inhibits dopamine neurons in substantia nigra pars compacta and the ventral tegmental area, with activation in the lateral habenula linking to deactivation in them, and vice versa, deactivation in the lateral habenula with their activation.<ref>{{cite journal | last1 = Matsumoto | first1 = M | last2 = Hikosaka | first2 = O | year = 2007 | title = Lateral habenula as a source of negative reward signals in dopamine neurons | url = | journal = Nature | volume = 447 | issue = 7148| pages = 1111–5 | pmid = 17522629 | doi=10.1038/nature05860}}</ref> The lateral habenula functions to oppose the action of the laterodorsal tegmental nucleus in the acquisition of [[avoidance response]]s but not the processing of avoidance later on when it is a memory, motivation or its execution.<ref>{{cite journal | last1 = Shumake | first1 = J | last2 = Ilango | first2 = A | last3 = Scheich | first3 = H | last4 = Wetzel | first4 = W | last5 = Ohl | first5 = FW | year = 2010 | title = Differential Neuromodulation of Acquisition and Retrieval of Avoidance Learning by the Lateral Habenula and Ventral Tegmental Area | url = | journal = Journal of Neuroscience | volume = 30 | issue = 17| pages = 5876–5883 | doi = 10.1523/JNEUROSCI.3604-09.2010 }}</ref> New research suggests that lateral habenula may play a crucial role in decision making.<ref>http://www.sciencedaily.com/releases/2013/11/131124200554.htm</ref>


===Medial habenula===
===Medial habenula===
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==Functions==
==Functions==


The habenular nuclei are involved in pain processing, reproductive behavior, nutrition, sleep-wake cycles, stress responses, and learning.<ref name="Andres"/> Recent demonstrations using [[fMRI]]<ref>Ullsperger, M; von Cramon, DY (2003). "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". Journal of Neuroscience 23 (10): 4308–4314. PMID 12764119</ref> and single unit electrophysiology<ref>Matsumoto, M; Hikosaka O (2007). "Lateral habenula as a source of negative reward signals in dopamine neurons.". ''Nature'' 447 (7148): 1111–1115. {{doi|10.1038/nature05860}} PMID 17522629.</ref> have closely linked the function of the lateral habenula with reward processing, in particular with regard to encoding negative feedback or negative rewards. Matsumoto and Hikosaka suggested in 2007 that this reward and reward-negative information in the brain might "be elaborated through the interplay among the lateral habenula, the basal ganglia, and monoaminergic (dopaminergic and serotonergic) systems" and that the lateral habenula may play a pivotal role in this "integrative function".<ref>Matsumoto, Hikosaka, 2007</ref> Recent evidence suggests that neurons in the lateral habenula signal signed information-prediction errors in addition to signed reward-prediction errors.<ref>Bromberg-Martin, E. S. & Hikosaka, O. Lateral habenula neurons signal errors in the prediction of reward information. Nature Neuroscience 14, 1209-1216 (2011). {{doi|10.1038/nn.2902}}</ref>
The habenular nuclei are involved in pain processing, reproductive behavior, nutrition, sleep-wake cycles, stress responses, and learning.<ref name="Andres"/> Recent demonstrations using [[fMRI]]<ref>{{cite journal | last1 = Ullsperger | first1 = M | last2 = von Cramon | first2 = DY | year = 2003 | title = 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 | url = | journal = Journal of Neuroscience | volume = 23 | issue = 10| pages = 4308–4314 | pmid = 12764119 }}</ref> and single unit electrophysiology<ref>{{cite journal | last1 = Matsumoto | first1 = M | last2 = Hikosaka | first2 = O | year = 2007 | title = Lateral habenula as a source of negative reward signals in dopamine neurons.". | url = | journal = Nature | volume = 447 | issue = 7148| pages = 1111–1115 | doi = 10.1038/nature05860 | pmid = 17522629 }}</ref> have closely linked the function of the lateral habenula with reward processing, in particular with regard to encoding negative feedback or negative rewards. Matsumoto and Hikosaka suggested in 2007 that this reward and reward-negative information in the brain might "be elaborated through the interplay among the lateral habenula, the basal ganglia, and monoaminergic (dopaminergic and serotonergic) systems" and that the lateral habenula may play a pivotal role in this "integrative function".<ref>Matsumoto, Hikosaka, 2007</ref> Recent evidence suggests that neurons in the lateral habenula signal signed information-prediction errors in addition to signed reward-prediction errors.<ref>Bromberg-Martin, E. S. & Hikosaka, O. "Lateral habenula neurons signal errors in the prediction of reward information" ''Nature Neuroscience'' 2011; 14, 1209-1216 {{doi|10.1038/nn.2902}}</ref>


==Depression==
==Depression==


Both the medial and lateral habenula show reduced volume in those with [[Major depressive disorder|depression]]. Neuron cell numbers were also reduced on the right side.<ref name="Ranft"/> Such changes are not seen in those with [[schizophrenia]].<ref name="Ranft">Ranft K, Dobrowolny H, Krell D, Bielau H, Bogerts B, Bernstein HG. (2010). Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia. Psychol Med. Apr;40(4):557-67. {{doi|10.1017/S0033291709990821}} PMID 19671211</ref> [[Deep brain stimulation]] of the major afferent bundle (i.e., stria medullaris thalami) of the lateral habenula has been used for treatment of depression where it is severe, protracted and therapy-resistant.<ref>Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, Henn FA, Meyer-Lindenberg A. (2010)). Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry. 15;67(2):e9-e11. {{doi|10.1016/j.biopsych.2009.08.027}} PMID 19846068</ref><ref>Juckel G, Uhl I, Padberg F, Brüne M, Winter C. (2009). Psychosurgery and deep brain stimulation as ultima ratio treatment for refractory depression. Eur Arch Psychiatry Clin Neurosci. Feb;259(1):1-7. PMID 19137233</ref>
Both the medial and lateral habenula show reduced volume in those with [[Major depressive disorder|depression]]. Neuron cell numbers were also reduced on the right side.<ref name="Ranft"/> Such changes are not seen in those with [[schizophrenia]].<ref name="Ranft">Ranft K, Dobrowolny H, Krell D, Bielau H, Bogerts B, Bernstein HG. (2010). Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia. ''Psychol Med.'' 2010 Apr;40(4):557-67. {{doi|10.1017/S0033291709990821}} PMID 19671211</ref> [[Deep brain stimulation]] of the major afferent bundle (i.e., stria medullaris thalami) of the lateral habenula has been used for treatment of depression where it is severe, protracted and therapy-resistant.<ref>Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, Henn FA, Meyer-Lindenberg A. (2010). Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient" ''Biol Psychiatry'' 15;67(2):e9-e11. {{doi|10.1016/j.biopsych.2009.08.027}} PMID 19846068</ref><ref>{{cite journal | pmid = 19137233 | doi=10.1007/s00406-008-0826-7 | volume=259 | issue=1 | title=Psychosurgery and deep brain stimulation as ultima ratio treatment for refractory depression | date=February 2009 | journal=Eur Arch Psychiatry Clin Neurosci | pages=1–7}}</ref>


==External links==
==External links==

Revision as of 12:20, 21 December 2015

Habenula
Mesal aspect of a brain sectioned in the median sagittal plane. Habenula is not labeled directly, but after expanding, look to region with 'habenular commissure', 'pineal body', and 'posterior commissure'
1. Taenia choroidea (and lateral: Lamina affixa, Stria terminalis)
2. Thalamus, Pulvinar thalami
3. Third ventricle
4. Stalk of pineal gland
5. Habenula
6. Stria medullaris
7. Superior colliculus
8. Brachium of superior colliculus
9. Inferior colliculus
10. Brachium of inferior colliculus
11. Medial geniculate nucleus
12. Sulcus medianus
13. Superior cerebellar peduncles
14. Inferior cerebellar peduncle
15. Middle cerebellar peduncles
16. Tuberculum anterius thalami
17. Obex, Area postrema
Identifiers
MeSHD019262
NeuroNames294
NeuroLex IDbirnlex_1611
TA98A14.1.08.003
TA25662
FMA62032
Anatomical terms of neuroanatomy

In neuroanatomy, habenula (diminutive of Latin habena meaning rein) originally denoted the stalk of the pineal gland (pineal habenula; pedunculus of pineal body), but gradually came to refer to a neighboring group of nerve cells with which the pineal gland was believed to be associated, the habenular nucleus. The habenular nucleus is a set of well-conserved structures in all vertebrate animals.[1]

Currently, the Terminologia Anatomica term refers exclusively to this separate cell mass in the caudal and dorsal aspect of the dorsal thalamus (the epithalamus), embedded in the posterior end of the medullary stria from which it receives most of its afferent fibers. By way of the fasciculus retroflexus (habenulointerpeduncular tract) it projects to the interpeduncular nucleus and other paramedian cell groups of the midbrain tegmentum.

The habenula receives input from the brain via the stria medullaris thalami and outputs to many midbrain areas involved in releasing neurotransmitters, such as dopamine, norepinephrine, and serotonin.

Anatomy

The habenula was traditionally divided into lateral (limbic) and medial (motor) parts. Detailed examination of the region in the cat, however, suggested that the lateral part should be further divided into ten distinct subnuclei and the medial into five distinct subnuclei.[2]

Lateral habenula

The primary input regions to the lateral habenula are the lateral preoptic area (bringing input from the hippocampus and lateral septum), the ventral pallidum (bringing input from the nucleus accumbens and mediodorsal nucleus of the thalamus), the lateral hypothalamus, the medial habenula, and the internal segment of the globus pallidus (bringing input from other basal ganglia structures).[3]

Neurons in the lateral habenula are ‘reward-negative’ as they are activated by stimulus associated with unpleasant events, the absence of the reward or punishment especially when this is unpredictable.[4] Reward information to the lateral habenula comes from the internal part of the globus pallidus.[5]

The outputs of the lateral habenula target dopaminergic regions (substantia nigra pars compacta and the ventral tegmental area), serotonergic regions (median raphe and dorsal raphe nuclei), and a cholinergic region (the laterodorsal tegmental nucleus).[3] This output inhibits dopamine neurons in substantia nigra pars compacta and the ventral tegmental area, with activation in the lateral habenula linking to deactivation in them, and vice versa, deactivation in the lateral habenula with their activation.[6] The lateral habenula functions to oppose the action of the laterodorsal tegmental nucleus in the acquisition of avoidance responses but not the processing of avoidance later on when it is a memory, motivation or its execution.[7] New research suggests that lateral habenula may play a crucial role in decision making.[8]

Medial habenula

Input to the medial habenula comes from a variety of regions and carries a number of different chemicals. Input regions include septal nuclei (the nucleus fimbrialis septi and the nucleus triangularis septi), dopaminergic inputs from the interfascicular nucleus of the ventral tegmental area, noradrenergic inputs from the locus ceruleus, and GABAergic inputs from the diagonal band of Broca. The medial habenula sends outputs of glutamate, substance P and acetylcholine to the interpeduncular nucleus as well as to the pineal gland.[9][10]

Olfactory coding in the habenula

In lower vertebrates (lampreys and teleost fishes), mitral cell (principal olfactory neurons) axons project exclusively to the right hemisphere of the habenula in an asymmetric manner. It is reported that the dorsal habenula (Hb) are functional asymmetric with predominant odor responses in right hemisphere. Interestingly, it was also shown that Hb neurons are spontaneous active even in absence of olfactory stimulation. These spontaneous active Hb neurons are organized into functional clusters which were proposed to govern olfactory responses. (Jetti, SK. et al 2014, Current Biology)

Functions

The habenular nuclei are involved in pain processing, reproductive behavior, nutrition, sleep-wake cycles, stress responses, and learning.[1] Recent demonstrations using fMRI[11] and single unit electrophysiology[12] have closely linked the function of the lateral habenula with reward processing, in particular with regard to encoding negative feedback or negative rewards. Matsumoto and Hikosaka suggested in 2007 that this reward and reward-negative information in the brain might "be elaborated through the interplay among the lateral habenula, the basal ganglia, and monoaminergic (dopaminergic and serotonergic) systems" and that the lateral habenula may play a pivotal role in this "integrative function".[13] Recent evidence suggests that neurons in the lateral habenula signal signed information-prediction errors in addition to signed reward-prediction errors.[14]

Depression

Both the medial and lateral habenula show reduced volume in those with depression. Neuron cell numbers were also reduced on the right side.[15] Such changes are not seen in those with schizophrenia.[15] Deep brain stimulation of the major afferent bundle (i.e., stria medullaris thalami) of the lateral habenula has been used for treatment of depression where it is severe, protracted and therapy-resistant.[16][17]

External links

References

  1. ^ a b Andres, KH; During MV, Veh RW (1999). "Subnuclear organization of the rat habenular complexes." Journal of Comparative Neurology 407 (1): 130–150. doi:10.1002/(SICI)1096-9861(19990428)407:1<130::AID-CNE10>3.0.CO;2-8 PMID 10213193
  2. ^ Iwahori, N (1977). "A Golgi study on the habenular nucleus of the cat.". Journal of Comparative Neurology 72 (3): 319–344. PMID 319124
  3. ^ a b Geisler, S; Trimble, M (2008). "The lateral habenula: no longer neglected.". CNS Spectrums 13 (6): 484–489. PMID 18567972
  4. ^ Matsumoto M, Hikosaka O. (2009). Representation of negative motivational value in the primate lateral habenula. Nat Neurosci. 12(1):77-84. PMID 19043410
  5. ^ Hong S, Hikosaka O. (2008). The globus pallidus sends reward-related signals to the lateral habenula. Neuron. 60(4):720-9. PMID 19038227
  6. ^ Matsumoto, M; Hikosaka, O (2007). "Lateral habenula as a source of negative reward signals in dopamine neurons". Nature. 447 (7148): 1111–5. doi:10.1038/nature05860. PMID 17522629.
  7. ^ Shumake, J; Ilango, A; Scheich, H; Wetzel, W; Ohl, FW (2010). "Differential Neuromodulation of Acquisition and Retrieval of Avoidance Learning by the Lateral Habenula and Ventral Tegmental Area". Journal of Neuroscience. 30 (17): 5876–5883. doi:10.1523/JNEUROSCI.3604-09.2010.
  8. ^ http://www.sciencedaily.com/releases/2013/11/131124200554.htm
  9. ^ Lecourtier, Lucas; Kelly, Peter H. (January 2007). "A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition". Neuroscience & Biobehavioral Reviews. 31 (5): 658–672. doi:10.1016/j.neubiorev.2007.01.004.
  10. ^ Antolin-Fontes, B; Ables, JL; Görlich, A; Ibañez-Tallon, I (September 2015). "The habenulo-interpeduncular pathway in nicotine aversion and withdrawal". Neuropharmacology. 96 (Pt B): 213–22. doi:10.1016/j.neuropharm.2014.11.019. PMID 25476971.
  11. ^ Ullsperger, M; von Cramon, DY (2003). "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". Journal of Neuroscience. 23 (10): 4308–4314. PMID 12764119.
  12. ^ Matsumoto, M; Hikosaka, O (2007). "Lateral habenula as a source of negative reward signals in dopamine neurons."". Nature. 447 (7148): 1111–1115. doi:10.1038/nature05860. PMID 17522629.
  13. ^ Matsumoto, Hikosaka, 2007
  14. ^ Bromberg-Martin, E. S. & Hikosaka, O. "Lateral habenula neurons signal errors in the prediction of reward information" Nature Neuroscience 2011; 14, 1209-1216 doi:10.1038/nn.2902
  15. ^ a b Ranft K, Dobrowolny H, Krell D, Bielau H, Bogerts B, Bernstein HG. (2010). Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia. Psychol Med. 2010 Apr;40(4):557-67. doi:10.1017/S0033291709990821 PMID 19671211
  16. ^ Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, Henn FA, Meyer-Lindenberg A. (2010). Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient" Biol Psychiatry 15;67(2):e9-e11. doi:10.1016/j.biopsych.2009.08.027 PMID 19846068
  17. ^ "Psychosurgery and deep brain stimulation as ultima ratio treatment for refractory depression". Eur Arch Psychiatry Clin Neurosci. 259 (1): 1–7. February 2009. doi:10.1007/s00406-008-0826-7. PMID 19137233. 
18. SK Jetti, N Vendrell-Llopis, E Yaksi. Spontaneous activity governs olfactory representations in spatially organized habenular microcircuits. Current Biology 24 (4), 434-439
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