Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking

Nature Neuroscience volume 17, pages 577–585 (2014)Cite this article

Subjects

Abstract

The ventral pallidum is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to the ventral tegmental area (VTA) regulates neuronal activity there. However, the ventral pallidum is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. We found that projections to VTA from the rostral ventral pallidum (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated during cue-induced reinstatement of cocaine seeking—a rat model of relapse in addiction. Moreover, designer receptor–mediated transient inactivation of RVP neurons, their terminals in VTA or functional connectivity between RVP and VTA dopamine neurons blocked the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked cocaine-primed, but not cue-induced, reinstatement. This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: hM4Di inhibitory DREADD expression and function.
Figure 2: Effects of inactivating the rostral or caudal ventral pallidum on reinstatement of cocaine seeking.
Figure 3: Rostral ventral pallidum projections to VTA are Fos activated during cued reinstatement.
Figure 4: Inactivating rostral ventral pallidum afferents modulates VTA cell firing.
Figure 5: Inactivating rostral ventral pallidum projection to VTA blocks cued reinstatement.
Figure 6: Functional disconnection of rostral ventral pallidum projection to VTA dopamine neurons blocks cue-induced reinstatement.
Figure 7: GABAA-mediated disinhibition of VTA dopamine neurons enhances cue-induced reinstatement.

Similar content being viewed by others

References

  1. Zahm, D.S. & Heimer, L. Two transpallidal pathways originating in the rat nucleus accumbens. J. Comp. Neurol. 302, 437–446 (1990).

    Article  CAS  Google Scholar 

  2. Zahm, D.S., 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. 364, 340–362 (1996).

    Article  CAS  Google Scholar 

  3. Kalivas, P.W., Churchill, L. & Klitenick, M.A. GABA and enkephalin projection from the nucleus accumbens and ventral pallidum to the ventral tegmental area. Neuroscience 57, 1047–1060 (1993).

    Article  CAS  Google Scholar 

  4. Haber, S.N. & Nauta, W.J. Ramifications of the globus pallidus in the rat as indicated by patterns of immunohistochemistry. Neuroscience 9, 245–260 (1983).

    Article  CAS  Google Scholar 

  5. Floresco, S.B., West, A.R., Ash, B., Moore, H. & Grace, A.A. Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nat. Neurosci. 6, 968–973 (2003).

    Article  CAS  Google Scholar 

  6. Smith, K.S., Tindell, A.J., Aldridge, J.W. & Berridge, K.C. Ventral pallidum roles in reward and motivation. Behav. Brain Res. 196, 155–167 (2009).

    Article  Google Scholar 

  7. Mogenson, G.J., Brudzynski, S.M., Wu, M., Yang, C.Y. & Yim, C.Y. From motivation to action: a review of dopaminergic regulation of limbic to nucleus accumbens to ventral pallidum to pedunculopontine nucleus circuitries involved in limbic-motor integration. in Limbic Motor Circuits in Neuropsychiatry (eds. Kalivas, P.W. & Barnes, C.D.) 193–236 (CRC Press, Boca Raton, Florida, 1993).

  8. Churchill, L. & Kalivas, P.W. A topographically organized γ-aminobutyric acid projection from the ventral pallidum to the nucleus accumbens in the rat. J. Comp. Neurol. 345, 579–595 (1994).

    Article  CAS  Google Scholar 

  9. Heimer, L., Zahm, D.S., Churchill, L., Kalivas, P.W. & Wohltmann, C. Specificity in the projection patterns of accumbal core and shell in the rat. Neuroscience 41, 89–125 (1991).

    Article  CAS  Google Scholar 

  10. Kupchik, Y.M. & Kalivas, P.W. The rostral subcommissural ventral pallidum is a mix of ventral pallidal neurons and neurons from adjacent areas: an electrophysiological study. Brain Struct. Funct. 218, 1487–1500 (2013).

    Article  Google Scholar 

  11. Root, D.H. et al. Differential roles of ventral pallidum subregions during cocaine self-administration behaviors. J. Comp. Neurol. 521, 558–588 (2013).

    Article  CAS  Google Scholar 

  12. Yang, C.R. & Mogenson, G.J. Ventral pallidal neuronal responses to dopamine receptor stimulation in the nucleus accumbens. Brain Res. 489, 237–246 (1989).

    Article  CAS  Google Scholar 

  13. McBride, W.J., Murphy, J.M. & Ikemoto, S. Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. Behav. Brain Res. 101, 129–152 (1999).

    Article  CAS  Google Scholar 

  14. Panagis, G., Miliaressis, E., Anagnostakis, Y. & Spyraki, C. Ventral pallidum self-stimulation: a moveable electrode mapping study. Behav. Brain Res. 68, 165–172 (1995).

    Article  CAS  Google Scholar 

  15. Bengtson, C.P. & Osborne, P.B. Electrophysiological properties of cholinergic and noncholinergic neurons in the ventral pallidal region of the nucleus basalis in rat brain slices. J. Neurophysiol. 83, 2649–2660 (2000).

    Article  CAS  Google Scholar 

  16. Zahm, D.S. & Heimer, L. Ventral striatopallidal parts of the basal ganglia in the rat: I. Neurochemical compartmentation as reflected by the distributions of neurotensin and substance P immunoreactivity. J. Comp. Neurol. 272, 516–535 (1988).

    Article  CAS  Google Scholar 

  17. Johnson, P.I., Stellar, J.R. & Paul, A.D. Regional reward differences within the ventral pallidum are revealed by microinjections of a μ opiate receptor agonist. Neuropharmacology 32, 1305–1314 (1993).

    Article  CAS  Google Scholar 

  18. Calder, A.J. et al. Disgust sensitivity predicts the insula and pallidal response to pictures of disgusting foods. Eur. J. Neurosci. 25, 3422–3428 (2007).

    Article  Google Scholar 

  19. Smith, K.S. & Berridge, K.C. The ventral pallidum and hedonic reward: neurochemical maps of sucrose “liking” and food intake. J. Neurosci. 25, 8637–8649 (2005).

    Article  CAS  Google Scholar 

  20. Grace, A.A., Floresco, S.B., Goto, Y. & Lodge, D.J. Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci. 30, 220–227 (2007).

    Article  CAS  Google Scholar 

  21. Tindell, A.J., Berridge, K.C. & Aldridge, J.W. Ventral pallidal representation of pavlovian cues and reward: population and rate codes. J. Neurosci. 24, 1058–1069 (2004).

    Article  CAS  Google Scholar 

  22. Tachibana, Y. & Hikosaka, O. The primate ventral pallidum encodes expected reward value and regulates motor action. Neuron 76, 826–837 (2012).

    Article  CAS  Google Scholar 

  23. Mahler, S.V. & Aston-Jones, G.S. Fos activation of selective afferents to ventral tegmental area during cue-induced reinstatement of cocaine seeking in rats. J. Neurosci. 32, 13309–13326 (2012).

    Article  CAS  Google Scholar 

  24. Armbruster, B.N., Li, X., Pausch, M.H., Herlitze, S. & Roth, B.L. Evolving the lock to fit the key to create a family of G protein–coupled receptors potently activated by an inert ligand. Proc. Natl. Acad. Sci. USA 104, 5163–5168 (2007).

    Article  Google Scholar 

  25. Ferguson, S.M. & Neumaier, J.F. Grateful DREADDs: engineered receptors reveal how neural circuits regulate behavior. Neuropsychopharmacology 37, 296–297 (2012).

    Article  Google Scholar 

  26. Ungless, M.A. & Grace, A.A. Are you or aren't you? Challenges associated with physiologically identifying dopamine neurons. Trends Neurosci. 35, 422–430 (2012).

    Article  CAS  Google Scholar 

  27. Ikemoto, S. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res. Rev. 56, 27–78 (2007).

    Article  CAS  Google Scholar 

  28. Morales, M. & Pickel, V.M. Insights to drug addiction derived from ultrastructural views of the mesocorticolimbic system. Ann. NY Acad. Sci. 1248, 71–88 (2012).

    Article  CAS  Google Scholar 

  29. Fields, H.L., Hjelmstad, G.O., Margolis, E.B. & Nicola, S.M. Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. Annu. Rev. Neurosci. 30, 289–316 (2007).

    Article  CAS  Google Scholar 

  30. van Zessen, R., Phillips, J.L., Budygin, E.A. & Stuber, G.D. Activation of VTA GABA neurons disrupts reward consumption. Neuron 73, 1184–1194 (2012).

    Article  CAS  Google Scholar 

  31. Stamatakis, A.M. et al. A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward. Neuron 80, 1039–1053 (2013).

    Article  CAS  Google Scholar 

  32. Hjelmstad, G.O., Xia, Y., Margolis, E.B. & Fields, H.L. Opioid modulation of ventral pallidal afferents to ventral tegmental area neurons. J. Neurosci. 33, 6454–6459 (2013).

    Article  CAS  Google Scholar 

  33. Witten, I.B. et al. Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Neuron 72, 721–733 (2011).

    Article  CAS  Google Scholar 

  34. Geisler, S., Derst, C., Veh, R.W. & Zahm, D.S. Glutamatergic afferents of the ventral tegmental area in the rat. J. Neurosci. 27, 5730–5743 (2007).

    Article  CAS  Google Scholar 

  35. McFarland, K. & Kalivas, P.W. The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J. Neurosci. 21, 8655–8663 (2001).

    Article  CAS  Google Scholar 

  36. McFarland, K., Davidge, S.B., Lapish, C.C. & Kalivas, P.W. Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine-seeking behavior. J. Neurosci. 24, 1551–1560 (2004).

    Article  CAS  Google Scholar 

  37. Robledo, P. & Koob, G.F. Two discrete nucleus accumbens projection areas differentially mediate cocaine self-administration in the rat. Behav. Brain Res. 55, 159–166 (1993).

    Article  CAS  Google Scholar 

  38. Farrar, A.M. et al. Forebrain circuitry involved in effort-related choice: injections of the GABAA agonist muscimol into ventral pallidum alter response allocation in food-seeking behavior. Neuroscience 152, 321–330 (2008).

    Article  CAS  Google Scholar 

  39. Colussi-Mas, J., Geisler, S., Zimmer, L., Zahm, D.S. & Berod, A. Activation of afferents to the ventral tegmental area in response to acute amphetamine: a double-labelling study. Eur. J. Neurosci. 26, 1011–1025 (2007).

    Article  Google Scholar 

  40. Geisler, S. et al. Prominent activation of brainstem and pallidal afferents of the ventral tegmental area by cocaine. Neuropsychopharmacology 33, 2688–2700 (2008).

    Article  CAS  Google Scholar 

  41. Childress, A.R. et al. Prelude to passion: limbic activation by “unseen” drug and sexual cues. PLoS ONE 3, e1506 (2008).

    Article  Google Scholar 

  42. Zahm, D.S. Is the caudomedial shell of the nucleus accumbens part of the extended amygdala? A consideration of connections. Crit. Rev. Neurobiol. 12, 245–265 (1998).

    Article  CAS  Google Scholar 

  43. Tripathi, A., Prensa, L. & Mengual, E. Axonal branching patterns of ventral pallidal neurons in the rat. Brain Struct. Funct. 218, 1133–1157 (2013).

    Article  Google Scholar 

  44. Leung, B.K. & Balleine, B.W. The ventral striato-pallidal pathway mediates the effect of predictive learning on choice between goal-directed actions. J. Neurosci. 33, 13848–13860 (2013).

    Article  CAS  Google Scholar 

  45. Robinson, M.J. & Berridge, K.C. Instant transformation of learned repulsion into motivational “wanting.”. Curr. Biol. 23, 282–289 (2013).

    Article  CAS  Google Scholar 

  46. Lammel, S. et al. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron 57, 760–773 (2008).

    Article  CAS  Google Scholar 

  47. Luo, A.H., Georges, F.E. & Aston-Jones, G.S. Novel neurons in ventral tegmental area fire selectively during the active phase of the diurnal cycle. Eur. J. Neurosci. 27, 408–422 (2008).

    Article  Google Scholar 

  48. Robinson, T.E. & Berridge, K.C. Addiction. Annu. Rev. Psychol. 54, 25–53 (2003).

    Article  Google Scholar 

  49. Beckley, J.T., Evins, C.E., Fedarovich, H., Gilstrap, M.J. & Woodward, J.J. Medial prefrontal cortex inversely regulates toluene-induced changes in markers of synaptic plasticity of mesolimbic dopamine neurons. J. Neurosci. 33, 804–813 (2013).

    Article  CAS  Google Scholar 

  50. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic Press/Elsevier, Amsterdam, Boston, 2006).

Download references

Acknowledgements

We thank P. Do, M.J. Gilstrap and E.C. Lin for assistance with behavioral testing and immunohistochemistry and B.L. Roth (Department of Pharmacology, University of North Carolina) for DREADD constructs and consultation on DREADDs. CNO was supplied by US National Institutes of Health (NIH) National Cancer Institute (NCI) under the auspices of NS064882-01 and by the National Institute of Mental Health (NIMH) Chemical Synthesis and Drug Supply Program. Research was supported by NIH grants F32 DA026692, K99 DA035251 (S.V.M.), F31 DA030891 (J.T.B.), R21 DA025837 (G.A.-J. and S.P.W.), R01 DA013951 (J.J.W.), R37 DA006214 and P50 DA015369 (G.A.-J.). This project was supported by the National Center for Research Resources and the Office of the Director of the National Institutes of Health through grant number C06 RR015455.

Author information

Authors and Affiliations

  1. Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA

    Stephen V Mahler, Elena M Vazey, Jacob T Beckley, Colby R Keistler, Ellen M McGlinchey, Jennifer Kaufling, John J Woodward & Gary Aston-Jones

  2. Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, South Carolina, USA

    Steven P Wilson

  3. Department of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA

    Karl Deisseroth

Authors
  1. Stephen V Mahler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena M Vazey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacob T Beckley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Colby R Keistler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ellen M McGlinchey
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennifer Kaufling
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steven P Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Karl Deisseroth
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. John J Woodward
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gary Aston-Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.V.M. attained funding, designed and conducted experiments, performed surgeries, analyzed data and wrote the manuscript. E.M.V. designed and conducted anesthetized electrophysiology experiments, analyzed these data and wrote the manuscript. J.T.B. designed and conducted slice electrophysiology experiments, analyzed these data and wrote the manuscript. C.R.K. conducted behavioral experiments and wrote the manuscript. E.M.M. performed surgeries for and conducted behavioral and immunohistochemical experiments. J.K. conducted immunohistochemical and confocal microscopy experiments. S.P.W. attained funding and contributed the Syn-GFP viral construct. K.D. contributed the TH∷Cre transgenic rat line. J.J.W. attained funding, designed and conducted slice electrophysiology experiments and wrote the manuscript. G.A-J. attained funding, designed experiments and wrote the manuscript.

Corresponding author

Correspondence to Stephen V Mahler.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Double dissociation for rostral vs. caudal VP in cued vs. primed reinstatement.

a) RVP, CVP, and surrounding structures are represented in the horizontal plane. Boxed area is enlarged in panels b&c. ac: anterior commissure; IPAC: interstitial nucleus of the posterior limb of the anterior commissure; Lat. Shell: lateral nucleus accumbens shell; LH: lateral hypothalamus; POA: preoptic hypothalamic area; SLEA: sublenticular extended amygdala. b) Top panel shows m±SEM active lever pressing during cue-induced reinstatement in animals with containment of hM4Di expression >95% within RVP or CVP, after vehicle or CNO (20 mg/kg, i.p.). *p=0.015. Bottom panel represents effects in individual animals of CNO microinjections into various parts of VP on cued reinstatement. Location of each oval represents site of virus injections in behaviorally tested animals (bilateral virus placement represented on a unilateral map; two ovals/animal). Size and shape of ovals represents the average zone of hM4Di expression around virus injection sites [m±SEM spread: dorso-ventral: m=1.18(0.02) mm; medio-lateral: m=0.72(0.02); rostro-caudal: m=0.95(0.02)]. Color of ovals represents change in cue-induced reinstatement after CNO injection (expressed as percentage of vehicle day lever pressing in the same animal). Blues indicate decreases from vehicle day due to hM4Di inhibition, yellows and reds represent increases in reinstatement responding over vehicle day. c) Using the same symbol logic as panel b, effects of CNO (20 mg/kg, i.p.) on cocaine-primed reinstatement are shown for RVP and CVP hM4Di animals. Bars=m±SEM. *p<0.05

Supplementary Figure 2 Cue-induced reinstatement elicits Fos in VTA-projecting neurons in RVP, not CVP.

a) Coronal 40 μm thick section from RVP (∼0.6 mm rostral of bregma) showing typical staining for Fos (blue-black nuclear stain) and CTb (brown somatic stain, indicating VTA-projecting neurons). Scale bar=1 mm. Expression typical of behaviorally tested CS+ group, n=8. b) Coronal 40 μm thick section from CVP (∼0.4 mm caudal of bregma) showing typical staining for Fos and CTb. Scale bar=1 mm. Expression typical of behaviorally tested CS+ group, n=8. c) Higher magnification view of Fos and CTb staining in RVP. Arrows indicate co-labeled cells. Scale bar=50 μm. d) Fos activation of VTA-projecting cells (%CTb cells that are Fos+; y-axis) in brain slices taken from various rostro-caudal levels of VP (mm rostral or caudal of bregma; x-axis). Symbols indicate the behavioral test prior to sacrifice (red diamonds: CS+ reinstatement, blue squares: control CS- cue, pink triangles: extinction test, black Xs: novel environment locomotor test). Note that the samples in which the greatest proportion of VTA-projecting neurons expressed Fos were in CS+ animals, and were located rostral of bregma (in RVP).

Supplementary Figure 3 Projection patterns of RVP and CVP to VTA.

a) RVP and CVP projections to rostral and caudal VTA are illustrated in the horizontal plane. b) Mean±SEM CTb+ cells/sample located in RVP (left) or CVP (right), projecting to either rostral or caudal VTA. CTb injections were localized to VTA either entirely rostral of the interpeduncular nucleus (blue bars), or entirely caudal of it (red bars). These animals also supplied data for a previous publication23, where additional details on CTb injection sites can be found. c) Mean±SEM total CTb+ cells/slice at various levels throughout the rostro-caudal axis of VP after CTb injection in VTA. Lines=m±SEM. d) Example of axonal labeling for the HA-tagged hM4Di receptor in midbrain after injection of Syn-hM4Di-HA-GFP into RVP. Strong axonal hM4Di expression (black) was seen in lateral VTA, and ventromedial SN (pars compacta). Scale bar=500 μm. Inset shows 60X magnification of axon terminals expressing HA (black) in the vicinity of VTA cells (red Nissl stained), scale bar=50 μm. The sample sizes of experimental groups with equivalent axonal DREADD expression in ventral midbrain are listed in Results. (e) Example of axonal labeling for the HA-tagged hM4Di receptor in midbrain after injection of Syn-hM4Di-HA-GFP into CVP. The strongest axonal hM4Di expression was seen in SN (especially pars reticulata), though fibers were also observed in VTA (inset). Scale bar=500 μm. Inset shows 60X magnification of axon terminals expressing HA (black) in the vicinity of VTA cells (red Nissl stained), scale bar=50 μm. The sample sizes of experimental groups with equivalent axonal DREADD expression in ventral midbrain are listed in Results.

Supplementary Figure 4 No changes in VTA dopamine neuron inputs caused by CNO in GFP control virus rats.

a) Syn-GFP control lentivirus used to express GFP under a neuronal-specific human synapsin promoter (Syn) in RVP. b) Representative traces from VTA dopamine neurons are shown in baseline conditions (left, black), and after CNO (right, red; scale=20 pA, 200 ms). c) CNO had no effect on mean sIPSC amplitude. d) CNO had no effect on mean sIPSC frequency. Lines=individual raw values.

Supplementary Figure 5 Midbrain CNO microinjection sites.

Midbrain cannulae placements for microinjections of CNO into VTA or SN in animals tested for reinstatement of cocaine seeking. Animals with placements within VTA borders are shown with filled black circles, animals with placements outside VTA (including in SN) are shown with unfilled (white) circles.

Supplementary Figure 6 Example hM4Di expression in VTA TH+ neurons and processes.

Confocal photomicrographs of VTA in TH::Cre rats after injection of DIO-Syn-hM4Di-mCherry. Equivalent expression seen in behavioral tested animals, n=9. Dopamine cells are labeled for TH (green, top left), and nearly all co-express the mCherry-tagged hM4Di receptor (red, bottom left). Yellow cells indicate cells and their processes co-expressing dopamine and DREADDs. Scale bar=50 μm.

Supplementary Figure 7 Disconnection of RVP from VTA or VTA Glutamate.

a) Animals received unilateral RVP Syn-hM4Di-HA-GFP, and a chronic cannula into contralateral VTA, and were tested for cue-induced reinstatement on separate days after i.p. 10 mg/kg CNO and intra-VTA vehicle (Veh-CNO; unilateral RVP inactivation control group), i.p. CNO plus unilateral intra-VTA cocktail of the AMPA/NMDA antagonists CNQX/AP5 (A/C-CNO: RVP/VTA glutamate disconnect group), or i.p. CNO plus unilateral intra-VTA cocktail of GABAA/B agonists baclofen and muscimol (B/M-CNO: RVP/VTA disconnect group). Some animals also received unilateral intra-VTA B/M + i.p. veh. (B/M-Veh: Unilateral VTA inactivation control group). b) Disconnection of RVP from VTA reduced reinstatement relative to unilateral RVP inhibition control, but neither unilateral VTA inactivation, nor disconnecting RVP from glutamate inputs did so. *p<0.05 Bars=m±SEM

Supplementary Figure 8 Inhibiting RVP inputs does not affect spontaneous excitatory inputs to VTA dopamine neurons.

a) Representative traces from VTA dopamine neurons are shown in baseline conditions (black), and b) after CNO (red; scale=20 pA, 200 ms). c) CNO had no effect on mean sIPSC amplitude. d) CNO had no effect on mean sIPSC frequency. Lines=individual raw values.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8 (PDF 7363 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mahler, S., Vazey, E., Beckley, J. et al. Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking. Nat Neurosci 17, 577–585 (2014). https://doi.org/10.1038/nn.3664

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.3664

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing