Top

Published in:

Open Access 01-04-2022 | Original Article

Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens

Authors: Imre Kalló, Azar Omrani, Frank J. Meye, Han de Jong, Zsolt Liposits, Roger A. H. Adan

Published in: Brain Structure and Function | Issue 3/2022

Abstract

Orexin neurons are involved in homeostatic regulatory processes, including arousal and feeding, and provide a major input from the hypothalamus to the ventral tegmental area (VTA) of the midbrain. VTA neurons are a central hub processing reward and motivation and target the medial prefrontal cortex (mPFC) and the shell part of nucleus accumbens (NAcs). We investigated whether subpopulations of dopamine (DA) neurons in the VTA projecting either to the mPFC or the medial division of shell part of nucleus accumbens (mNAcs) receive differential input from orexin neurons and whether orexin exerts differential electrophysiological effects upon these cells. VTA neurons projecting to the mPFC or the mNAcs were traced retrogradely by Cav2-Cre virus and identified by expression of yellow fluorescent protein (YFP). Immunocytochemical analysis showed that a higher proportion of all orexin-innervated DA neurons projected to the mNAcs (34.5%) than to the mPFC (5.2%). Of all sampled VTA neurons projecting either to the mPFC or mNAcs, the dopaminergic (68.3 vs. 79.6%) and orexin-innervated DA neurons (68.9 vs. 64.4%) represented the major phenotype. Whole-cell current clamp recordings were obtained from fluorescently labeled neurons in slices during baseline periods and bath application of orexin A. Orexin similarly increased the firing rate of VTA dopamine neurons projecting to mNAcs (1.99 ± 0.61 Hz to 2.53 ± 0.72 Hz) and mPFC (0.40 ± 0.22 Hz to 1.45 ± 0.56 Hz). Thus, the hypothalamic orexin system targets mNAcs and to a lesser extent mPFC-projecting dopaminergic neurons of the VTA and exerts facilitatory effects on both clusters of dopamine neurons.

Albanese A, Minciacchi D (1983) Organization of the ascending projections from the ventral tegmental area: a multiple fluorescent retrograde tracer study in the rat. J Comp Neurol 216(4):406–420. https://doi.org/10.1002/cne.902160406CrossRefPubMed

Aston-Jones G, Smith RJ, Moorman DE, Richardson KA (2009) Role of lateral hypothalamic orexin neurons in reward processing and addiction. Neuropharmacology 56(Suppl 1):112–121. https://doi.org/10.1016/j.neuropharm.2008.06.060CrossRefPubMed

Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P, Richardson KA (2010) Lateral hypothalamic orexin/hypocretin neurons: a role in reward-seeking and addiction. Brain Res 1314:74–90. https://doi.org/10.1016/j.brainres.2009.09.106CrossRefPubMed

Baimel C, Borgland SL (2017) Hypocretin/orexin and plastic adaptations associated with drug abuse. Curr Top Behav Neurosci 33:283–304. https://doi.org/10.1007/7854_2016_44CrossRefPubMed

Baimel C, Lau BK, Qiao M, Borgland SL (2017) Projection-target-defined effects of orexin and dynorphin on VTA dopamine neurons. Cell Rep 18(6):1346–1355. https://doi.org/10.1016/j.celrep.2017.01.030CrossRefPubMed

Balcita-Pedicino JJ, Sesack SR (2007) Orexin axons in the rat ventral tegmental area synapse infrequently onto dopamine and gamma-aminobutyric acid neurons. J Comp Neurol 503(5):668–684. https://doi.org/10.1002/cne.21420CrossRefPubMed

Bartonjo JJ, Lundy RF (2020) Distinct populations of amygdala somatostatin-expressing neurons project to the nucleus of the solitary tract and parabrachial nucleus. Chem Senses 45(8):687–698. https://doi.org/10.1093/chemse/bjaa059CrossRefPubMedPubMedCentral

Beny-Shefer Y, Zilkha N, Lavi-Avnon Y, Bezalel N, Rogachev I, Brandis A, Dayan M, Kimchi T (2017) Nucleus accumbens dopamine signaling regulates sexual preference for females in male mice. Cell Rep 21(11):3079–3088. https://doi.org/10.1016/j.celrep.2017.11.062CrossRefPubMed

Björklund A, Dunnett SB (2007) Dopamine neuron systems in the brain: an update. Trends Neurosci 30(5):194–202. https://doi.org/10.1016/j.tins.2007.03.006CrossRefPubMed

Boender AJ, de Jong JW, Boekhoudt L, Luijendijk MC, van der Plasse G, Adan RA (2014) Combined use of the canine adenovirus-2 and DREADD-technology to activate specific neural pathways in vivo. PLoS ONE 9(4):e95392. https://doi.org/10.1371/journal.pone.0095392CrossRefPubMedPubMedCentral

Borgland SL, Taha SA, Sarti F, Fields HL, Bonci A (2006) Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 49(4):589–601. https://doi.org/10.1016/j.neuron.2006.01.016CrossRefPubMed

Breton JM, Charbit AR, Snyder BJ, Fong PTK, Dias EV, Himmels P, Lock H, Margolis EB (2019) Relative contributions and mapping of ventral tegmental area dopamine and GABA neurons by projection target in the rat. J Comp Neurol 527(5):916–941. https://doi.org/10.1002/cne.24572CrossRefPubMed

Brog JS, Salyapongse A, Deutch AY, Zahm DS (1993) The patterns of afferent innervation of the core and shell in the “accumbens” part of the rat ventral striatum: immunohistochemical detection of retrogradely transported fluoro-gold. J Comp Neurol 338(2):255–278. https://doi.org/10.1002/cne.903380209CrossRefPubMed

Bubar MJ, Cunningham KA (2007) Distribution of serotonin 5-HT2C receptors in the ventral tegmental area. Neuroscience 146(1):286–297. https://doi.org/10.1016/j.neuroscience.2006.12.071CrossRefPubMed

Buchta WC, Mahler SV, Harlan B, Aston-Jones GS, Riegel AC (2017) Dopamine terminals from the ventral tegmental area gate intrinsic inhibition in the prefrontal cortex. Physiol Rep. https://doi.org/10.14814/phy2.13198CrossRefPubMedPubMedCentral

Bullmann T, Hartig W, Holzer M, Arendt T (2010) Expression of the embryonal isoform (0N/3R) of the microtubule-associated protein tau in the adult rat central nervous system. J Comp Neurol 518(13):2538–2553. https://doi.org/10.1002/cne.22351CrossRefPubMed

Carr DB, Sesack SR (2000) Projections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons. J Neurosci 20(10):3864–3873CrossRef

Chandler DJ, Lamperski CS, Waterhouse BD (2013) Identification and distribution of projections from monoaminergic and cholinergic nuclei to functionally differentiated subregions of prefrontal cortex. Brain Res 1522:38–58. https://doi.org/10.1016/j.brainres.2013.04.057CrossRefPubMed

Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, Ferguson D, Tsai HC, Pomeranz L, Christoffel DJ, Nectow AR, Ekstrand M, Domingos A, Mazei-Robison MS, Mouzon E, Lobo MK, Neve RL, Friedman JM, Russo SJ, Deisseroth K, Nestler EJ, Han MH (2013) Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493(7433):532–536. https://doi.org/10.1038/nature11713CrossRefPubMed

Chou TC, Lee CE, Lu J, Elmquist JK, Hara J, Willie JT, Beuckmann CT, Chemelli RM, Sakurai T, Yanagisawa M, Saper CB, Scammell TE (2001) Orexin (hypocretin) neurons contain dynorphin. J Neurosci 21(19):RC168CrossRef

Corre J, van Zessen R, Loureiro M, Patriarchi T, Tian L, Pascoli V, Lüscher C (2018) Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement. Elife. https://doi.org/10.7554/eLife.39945CrossRefPubMedPubMedCentral

Dahlstroem A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl: SUPPL 232:231–255

Dal Bo G, St-Gelais F, Danik M, Williams S, Cotton M, Trudeau LE (2004) Dopamine neurons in culture express VGLUT2 explaining their capacity to release glutamate at synapses in addition to dopamine. J Neurochem 88(6):1398–1405. https://doi.org/10.1046/j.1471-4159.2003.02277.xCrossRef

Danjo T, Yoshimi K, Funabiki K, Yawata S, Nakanishi S (2014) Aversive behavior induced by optogenetic inactivation of ventral tegmental area dopamine neurons is mediated by dopamine D2 receptors in the nucleus accumbens. Proc Natl Acad Sci USA 111(17):6455–6460. https://doi.org/10.1073/pnas.1404323111CrossRefPubMedPubMedCentral

de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95(1):322–327. https://doi.org/10.1073/pnas.95.1.322CrossRefPubMedPubMedCentral

Dehkordi O, Rose JE, Dávila-García MI, Millis RM, Mirzaei SA, Manaye KF, Jayam-Trouth A (2017) Neuroanatomical relationships between orexin/hypocretin-containing neurons/nerve fibers and nicotine-induced c-Fos-activated cells of the reward-addiction neurocircuitry. J Alcohol Drug Depend. https://doi.org/10.4172/2329-6488.1000273CrossRefPubMedPubMedCentral

Del Cid-Pellitero E, Garzón M (2014) Hypocretin1/orexinA-immunoreactive axons form few synaptic contacts on rat ventral tegmental area neurons that project to the medial prefrontal cortex. BMC Neurosci 15:105. https://doi.org/10.1186/1471-2202-15-105CrossRefPubMedPubMedCentral

Deurveilher S, Lo H, Murphy JA, Burns J, Semba K (2006) Differential c-Fos immunoreactivity in arousal-promoting cell groups following systemic administration of caffeine in rats. J Comp Neurol 498(5):667–689. https://doi.org/10.1002/cne.21084CrossRefPubMed

España RA, Baldo BA, Kelley AE, Berridge CW (2001) Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action. Neuroscience 106(4):699–715. https://doi.org/10.1016/s0306-4522(01)00319-0CrossRefPubMed

España RA, Melchior JR, Roberts DC, Jones SR (2011) Hypocretin 1/orexin A in the ventral tegmental area enhances dopamine responses to cocaine and promotes cocaine self-administration. Psychopharmacology 214(2):415–426. https://doi.org/10.1007/s00213-010-2048-8CrossRefPubMed

Fadel J, Deutch AY (2002) Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area. Neuroscience 111(2):379–387. https://doi.org/10.1016/s0306-4522(02)00017-9CrossRefPubMed

Fallon JH, Moore RY (1978) Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J Comp Neurol 180(3):545–580. https://doi.org/10.1002/cne.901800310CrossRefPubMed

Farassat N, Costa KM, Stojanovic S, Albert S, Kovacheva L, Shin J, Egger R, Somayaji M, Duvarci S, Schneider G, Roeper J (2019) In vivo functional diversity of midbrain dopamine neurons within identified axonal projections. Elife. https://doi.org/10.7554/eLife.48408CrossRefPubMedPubMedCentral

Flores-Dourojeanni JP, van Rijt C, van den Munkhof MH, Boekhoudt L, Luijendijk MCM, Vanderschuren LJMJ, Adan RAH (2021) Temporally specific roles of ventral tegmental area projections to the nucleus accumbens and prefrontal cortex in attention and impulse control. J Neurosci 41(19):4293–4304. https://doi.org/10.1523/JNEUROSCI.0477-20.2020CrossRefPubMedPubMedCentral

Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, Maratos-Flier E, Flier JS (2006) Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51(6):811–822. https://doi.org/10.1016/j.neuron.2006.09.006CrossRefPubMed

Gorelova N, Mulholland PJ, Chandler LJ, Seamans JK (2012) The glutamatergic component of the mesocortical pathway emanating from different subregions of the ventral midbrain. Cereb Cortex 22(2):327–336. https://doi.org/10.1093/cercor/bhr107CrossRefPubMed

Harris GC, Wimmer M, Aston-Jones G (2005) A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437(7058):556–559. https://doi.org/10.1038/nature04071CrossRefPubMed

Hasue RH, Shammah-Lagnado SJ (2002) Origin of the dopaminergic innervation of the central extended amygdala and accumbens shell: a combined retrograde tracing and immunohistochemical study in the rat. J Comp Neurol 454(1):15–33. https://doi.org/10.1002/cne.10420CrossRefPubMed

Henny P, Brischoux F, Mainville L, Stroh T, Jones BE (2010) Immunohistochemical evidence for synaptic release of glutamate from orexin terminals in the locus coeruleus. Neuroscience 169(3):1150–1157. https://doi.org/10.1016/j.neuroscience.2010.06.003CrossRefPubMed

Horvath TL, Gao XB (2005) Input organization and plasticity of hypocretin neurons: possible clues to obesity’s association with insomnia. Cell Metab 1(4):279–286. https://doi.org/10.1016/j.cmet.2005.03.003CrossRefPubMed

Hrabovszky E, Molnár CS, Borsay B, Gergely P, Herczeg L, Liposits Z (2013) Orexinergic input to dopaminergic neurons of the human ventral tegmental area. PLoS ONE 8(12):e83029. https://doi.org/10.1371/journal.pone.0083029CrossRefPubMedPubMedCentral

James MH, Mahler SV, Moorman DE, Aston-Jones G (2017) A decade of orexin/hypocretin and addiction: where are we now? Curr Top Behav Neurosci 33:247–281. https://doi.org/10.1007/7854_2016_57CrossRefPubMedPubMedCentral

Kabanova A, Pabst M, Lorkowski M, Braganza O, Boehlen A, Nikbakht N, Pothmann L, Vaswani AR, Musgrove R, Di Monte DA, Sauvage M, Beck H, Blaess S (2015) Function and developmental origin of a mesocortical inhibitory circuit. Nat Neurosci 18(6):872–882. https://doi.org/10.1038/nn.4020CrossRefPubMed

Korotkova TM, Sergeeva OA, Eriksson KS, Haas HL, Brown RE (2003) Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J Neurosci 23(1):7–11CrossRef

Labouebe G, Lomazzi M, Cruz HG, Creton C, Lujan R, Li M et al (2007) RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Nat Neurosci 10:1559–1568CrossRef

Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, Deisseroth K, Malenka RC (2012) Input-specific control of reward and aversion in the ventral tegmental area. Nature 491(7423):212–217. https://doi.org/10.1038/nature11527CrossRefPubMedPubMedCentral

Lei K, Kwok C, Darevsky D, Wegner SA, Yu J, Nakayama L, Pedrozo V, Anderson L, Ghotra S, Fouad M, Hopf FW (2019) Nucleus accumbens shell orexin-1 receptors are critical mediators of binge intake in excessive-drinking individuals. Front Neurosci 13:88. https://doi.org/10.3389/fnins.2019.00088CrossRefPubMedPubMedCentral

Li B, Chang L, Peng X (2021) Orexin 2 receptor in the nucleus accumbens is critical for the modulation of acute stress-induced anxiety. Psychoneuroendocrinology 131:105317. https://doi.org/10.1016/j.psyneuen.2021.105317CrossRefPubMed

Margolis EB, Lock H, Chefer VI, Shippenberg TS, Hjelmstad GO, Fields HL (2006) Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proc Natl Acad Sci USA 103(8):2938–2942. https://doi.org/10.1073/pnas.0511159103CrossRefPubMedPubMedCentral

Maxwell SL, Ho HY, Kuehner E, Zhao S, Li M (2005) Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development. Dev Biol 282:467–479CrossRef

Moorman DE, Aston-Jones G (2010) Orexin/hypocretin modulates response of ventral tegmental dopamine neurons to prefrontal activation: diurnal influences. J Neurosci 30(46):15585–15599. https://doi.org/10.1523/JNEUROSCI.2871-10.2010CrossRefPubMedPubMedCentral

Morales M, Margolis EB (2017) Ventral tegmental area: cellular heterogeneity, connectivity and behaviour. Nat Rev Neurosci 18(2):73–85. https://doi.org/10.1038/nrn.2016.165CrossRefPubMed

Muschamp JW, Dominguez JM, Sato SM, Shen RY, Hull EM (2007) A role for hypocretin (orexin) in male sexual behavior. J Neurosci 27(11):2837–2845. https://doi.org/10.1523/JNEUROSCI.4121-06.2007CrossRefPubMedPubMedCentral

Neve RL (2012) Overview of gene delivery into cells using HSV-1-based vectors. Curr Protoc Neurosci. https://doi.org/10.1002/0471142301.ns0412s61 (Chapter 4:Unit 4.12)CrossRefPubMed

Papathanou M, Creed M, Dorst MC, Bimpisidis Z, Dumas S, Pettersson H, Bellone C, Silberberg G, Lüscher C, Wallén-Mackenzie Å (2018) Targeting VGLUT2 in mature dopamine neurons decreases mesoaccumbal glutamatergic transmission and identifies a role for glutamate co-release in synaptic plasticity by increasing baseline AMPA/NMDA ratio. Front Neural Circuits 12:64. https://doi.org/10.3389/fncir.2018.00064CrossRefPubMedPubMedCentral

Paxinos G, Franklin KBJ (2013) The mouse brain in stereotaxic coordinates, 4th edn. Elsevier, San Diego

Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates, 5th edn. Elsevier, Amsterdam

Pérez-López JL, Contreras-López R, Ramírez-Jarquín JO, Tecuapetla F (2018) Direct glutamatergic signaling from midbrain dopaminergic neurons onto pyramidal prefrontal cortex neurons. Front Neural Circuits 12:70. https://doi.org/10.3389/fncir.2018.00070CrossRefPubMedPubMedCentral

Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18(23):9996–10015CrossRef

Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92(4):573–585. https://doi.org/10.1016/s0092-8674(00)80949-6CrossRef

Sharf R, Sarhan M, Dileone RJ (2008) Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell. Biol Psychiatry 64(3):175–183. https://doi.org/10.1016/j.biopsych.2008.03.006CrossRefPubMedPubMedCentral

Smith RJ, Tahsili-Fahadan P, Aston-Jones G (2010) Orexin/hypocretin is necessary for context-driven cocaine-seeking. Neuropharmacology 58(1):179–184. https://doi.org/10.1016/j.neuropharm.2009.06.042CrossRefPubMed

Stott SR, Metzakopian E, Lin W, Kaestner KH, Hen R, Ang SL (2013) Foxa1 and foxa2 are required for the maintenance of dopaminergic properties in ventral midbrain neurons at late embryonic stages. J Neurosci 33(18):8022–8034. https://doi.org/10.1523/JNEUROSCI.4774-12.2013CrossRefPubMedPubMedCentral

Swanson LW (1982) The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 9(1–6):321–353. https://doi.org/10.1016/0361-9230(82)90145-9CrossRefPubMed

Trivedi P, Yu H, MacNeil DJ, Van der Ploeg LH, Guan XM (1998) Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438(1–2):71–75. https://doi.org/10.1016/s0014-5793(98)01266-6CrossRefPubMed

Tunisi L, D’Angelo L, Fernández-Rilo AC, Forte N, Piscitelli F, Imperatore R, de Girolamo P, Di Marzo V, Cristino L (2021) Orexin-A/hypocretin-1 controls the VTA-NAc mesolimbic pathway via endocannabinoid-mediated disinhibition of dopaminergic neurons in obese mice. Front Synaptic Neurosci 13:622405. https://doi.org/10.3389/fnsyn.2021.622405CrossRefPubMedPubMedCentral

Tzschentke TM (2001) Pharmacology and behavioral pharmacology of the mesocortical dopamine system. Prog Neurobiol 63(3):241–320. https://doi.org/10.1016/s0301-0082(00)00033-2CrossRefPubMed

Tzschentke TM, Schmidt WJ (2000) Functional relationship among medial prefrontal cortex, nucleus accumbens, and ventral tegmental area in locomotion and reward. Crit Rev Neurobiol 14(2):131–142CrossRef

Vittoz NM, Berridge CW (2006) Hypocretin/orexin selectively increases dopamine efflux within the prefrontal cortex: involvement of the ventral tegmental area. Neuropsychopharmacology 31(2):384–395. https://doi.org/10.1038/sj.npp.1300807CrossRefPubMed

Vittoz NM, Schmeichel B, Berridge CW (2008) Hypocretin /orexin preferentially activates caudomedial ventral tegmental area dopamine neurons. Eur J Neurosci 28(8):1629–1640. https://doi.org/10.1111/j.1460-9568.2008.06453.xCrossRefPubMedPubMedCentral

Yang H, de Jong JW, Tak Y, Peck J, Bateup HS, Lammel S (2018) Nucleus accumbens subnuclei regulate motivated behavior via direct inhibition and disinhibition of VTA dopamine subpopulations. Neuron 97(2):434-449.e434. https://doi.org/10.1016/j.neuron.2017.12.022CrossRefPubMedPubMedCentral

Yokofujita J, Oda S, Igarashi H, Sato F, Kuroda M (2008) Synaptic characteristics between cortical cells in the rat prefrontal cortex and axon terminals from the ventral tegmental area that utilize different neurotransmitters. Int J Neurosci 118(10):1443–1459. https://doi.org/10.1080/00207450701870253CrossRefPubMed

Zhao S, Maxwell S, Jimenez-Beristain A, Vives J, Kuehner E, Zhao J et al (2004) Generation of embryonic stem cells and transgenic mice expressing green fluorescence protein in midbrain dopaminergic neurons. Eur J Neurosci. 19:1133–1140CrossRef

Zheng H, Patterson LM, Berthoud HR (2007) Orexin signaling in the ventral tegmental area is required for high-fat appetite induced by opioid stimulation of the nucleus accumbens. J Neurosci 27(41):11075–11082. https://doi.org/10.1523/JNEUROSCI.3542-07.2007CrossRefPubMedPubMedCentral

Title: Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens
Authors: Imre Kalló
Azar Omrani
Frank J. Meye
Han de Jong
Zsolt Liposits
Roger A. H. Adan
Publication date: 01-04-2022
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 3/2022
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-021-02449-8

At a glance: The STEP trials

Springer Medicine

Characterization of orexin input to dopamine neurons of the ventral tegmental area projecting to the medial prefrontal cortex and shell of nucleus accumbens

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2022

Neural responses to facial attractiveness in the judgments of moral goodness and moral beauty

Study of the glial cytoarchitecture of the developing olfactory bulb of a shark using immunochemical markers of radial glia

Does a third intermediate model for the vomeronasal processing of information exist? Insights from the macropodid neuroanatomy

Discernible effects of tDCS over the primary motor and posterior parietal cortex on different stages of motor learning

Correction to: Comparing astrocytic gap junction of genetic absence epileptic rats with control rats: an experimental study

Medial temporal lobe contributions to resting-state networks