Cognitive, Behavioral and Systems NeuroscienceResearch PaperGlutamatergic axons from the lateral habenula mainly terminate on GABAergic neurons of the ventral midbrain
Section snippets
Chemicals
Chemicals were obtained from Sigma-Aldrich, Taufkirchen, Germany, if not indicated otherwise. Sources of primary antibodies are depicted in Table 1. Biotin-labeled secondary antibodies and the ABC-Elite complex were from Vector (Vector Laboratories, Burlingame, CA, USA) and gold-labeled secondary antibodies from Nanoprobes (Yaphank, NY, USA).
Animals
All animal experiments were conducted in accordance with the guidelines of the European Communities Council directive 86/609/EEC and were approved by the
Results
The inhibitory control of the lateral habenular complex (LHb) over the dopaminergic (DA) neurons in the VTA is well documented (see introduction). It is not known, whether this inhibition is due to a direct inhibitory (GABAergic or glycinergic) influence or due to an excitatory (cholinergic or glutamatergic) projection via inhibitory neurons in the ventral mesencephalon. Immunocytochemical screening of the LHb for glycinergic neurons with antibodies against the glycine transporter and for
Discussion
The prominent projections from the LHb complex to the ventral mesencephalon are well known (Phillipson, 1979, Herkenham and Nauta, 1979, Oades and Halliday, 1987, Geisler et al., 2007, Geisler and Trimble, 2008, Jhou et al., 2009a, Jhou et al., 2009b, Kaufling et al., 2009). In agreement with previous reports (Araki et al., 1988), we found that midbrain terminals from the LHb primarily project to the VTA and the tVTA/RMTg and only slightly to medial aspects of the substantia nigra pars compacta
Acknowledgments
This work was supported with help from Heike Heilmann and Ina Wolter in data collection, Gregor Laube in electron microscopy, Christian Derst in providing the riboprobes, and comments of René Bernard and Torsten Weiβ on a previous version of this manuscript. This work is part of the MD thesis of Katja Brinschwitz at the Institut für Integrative Neuroanatomie, Charité - Universitätsmedizin Berlin.
References (60)
- et al.
Functional architecture of basal ganglia circuits: neural substrates of parallel processing
Trends Neurosci
(1990) - et al.
The efferent projections of the rat lateral habenular nucleus revealed by the PHA-L anterograde tracing method
Brain Res
(1988) The neostriatal mosaic: multiple levels of compartmental organization
Trends Neurosci
(1992)- et al.
The Rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine neurons, encodes aversive stimuli and inhibits motor responses
Neuron
(2009) - et al.
A double labeling technique using WGA-apoHRP-gold as a retrograde tracer and non-isotopic in situ hybridization histochemistry for the detection of mRNA
J Neurosci Methods
(2000) Neurotransmitter regulation of dopamine neurons in the ventral tegmental area
Brain Res Rev
(1993)- et al.
Gamma-aminobutyric acid cells with cocaine-induced deltaFosB in the ventral tegmental area innervate mesolimbic neurons
Biol Psychiatry
(2010) - et al.
Dopaminergic activation excites rat lateral habenular neurons in vivo
Neuroscience
(2009) - et al.
Selective activation of the mesocortico-frontal dopaminergic neurons induced by lesions of the habenula in the rat
Brain Res
(1980) - et al.
Action of habenular efferents on ventral tegmental area neurons studied in vitro
Brain Res Bull
(1992)
Prefrontal cortex regulates burst firing and transmitter release in rat mesolimbic dopamine neurons studied in vivo
Neurosci Lett
Evidence for, and nature of, the tonic inhibitory influence of habenulointerpeduncular pathways upon cerebral dopaminergic transmission in the rat
Brain Res
Ventral tegmental (A 10) system: neurobiology. 1Anatomy and connectivity
Brain Res Rev
The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat
Brain Res Bull
GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain
Brain Res
Subpallidal outputs to the nucleus accumbens and the ventral tegmental area: anatomical and electrophysiological studies
Brain Res
General methods for characterization of brain regions
Subnuclear organization of the rat habenular complexes
J Comp Neurol
WGA-apo-HRP-gold: a new retrograde tracer for light- and electron-microscopic single—and double-label studies
J Comp Neurol
Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion
Proc Natl Acad Sci U S A
Glutamatergic fibers from the lateral habenula do not terminate on dopaminergic neurons in the ventral tegmental area
Soc Neurosci Abstr
GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex
Synapse
Burst firing of mesencephalic dopamine neurons is inhibited by somatodendritic application of kynurenate
Acta Physiol Scand
Tonic activation of NMDA receptors causes spontaneous burst discharge of rat midbrain dopamine neurons in vivo
Eur J Neurosci
Stimulation of the lateral habenula inhibits dopamine-containing neurons in the substantia nigra and ventral tegmentum area of the rat
J Neurosci
Anterior and posterior parts of the rat ventral tegmental area receive topographically distinct afferents from the lateral habenular complex
Soc Neurosci Abst Atlanta
Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms
J Neurosci
Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission
Nat Neurosci
Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area
Eur J Neurosci
Morphologic and cytochemical criteria for the identification and delineation of individual subnuclei within the lateral habenular complex of the rat
J Comp Neurol
Cited by (158)
Tet2 acts in the lateral habenula to regulate social preference in mice
2023, Cell ReportsTonic activity in lateral habenula neurons acts as a neutral valence brake on reward-seeking behavior
2022, Current BiologyCitation Excerpt :To compare these results with other methods used for recording LHb neural activity, we used fiber photometry to record the activity of genetically targeted glutamatergic LHb neurons in Vglut2-ires-Cre mice63 during performance of the same task (Figures S1A and S1B). Most neurons in the LHb are glutamatergic and express Vglut2,64 and Vglut2-ires-Cre mice have previously been used to target the LHb.65,66 We also recorded LHb neural activity in C57BL6/J mice using multi-unit electrophysiology (Figures S1E and S1F).
Functions of habenula in reproduction and socio-reproductive behaviours
2022, Frontiers in NeuroendocrinologyIlluminating subcortical GABAergic and glutamatergic circuits for reward and aversion
2021, Neuropharmacology
- 1
Present address: Unfallkrankenhaus Berlin, Klinik für Hals-, Nasen und Ohrenheilkunde, Warener Strasse, D-712683 Berlin, Germany.
- 2
Present address: Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Frauenheilkunde/Geburtshilfe, Bereich Gynäkologie–OP, Charitéplatz 1, D-10117 Berlin, Germany.
- 3
Present address: Department of Neurology, Washington University/Barnes Jewish Hospital, 1 BJH Plaza, St. Louis, MO 63110, USA.