Ventral arkypallidal neurons inhibit accumbal firing to promote reward consumption


The nucleus accumbens shell (NAcSh) and the ventral pallidum (VP) are critical for reward processing, although the question of how coordinated activity within these nuclei orchestrates reward valuation and consumption remains unclear. Inhibition of NAcSh firing is necessary for reward consumption, but the source of this inhibition remains unknown. Here, we report that a subpopulation of VP neurons, the ventral arkypallidal (vArky) neurons, project back to the NAcSh, where they inhibit NAcSh neurons in vivo in mice. Consistent with this pathway driving reward consumption via inhibition of the NAcSh, calcium activity of vArky neurons scaled with reward palatability (which was dissociable from reward seeking) and predicted the subsequent drinking behavior during a free-access paradigm. Activation of the VP–NAcSh pathway increased ongoing reward consumption while amplifying hedonic reactions to reward. These results establish a pivotal role for vArky neurons in the promotion of reward consumption through modulation of NAcSh firing in a value-dependent manner.

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Fig. 1: NAcSh inhibition is causally related to reward consumption.
Fig. 2: A subpopulation of VP neurons innervates projection neurons and interneurons in the NAcSh.
Fig. 3: VP neurons make inhibitory, monosynaptic contacts onto NAcSh neurons.
Fig. 4: Activation of vArky terminals inhibits NAcSh firing in vivo.
Fig. 5: vArky calcium activity is correlated with duration of reward consumption.
Fig. 6: Closed-loop activation of vArky terminals promotes reward consumption.
Fig. 7: Selective vArky inhibition attenuates consumption-related inhibition of NAcSh firing and reduces length of reward consumption bouts.
Fig. 8: vArky activation enhances reward value and vArky calcium activity scales with reward palatability.

Data availability

The data that support the findings of this study are available from the corresponding author upon request. Analysis code will be provided from authors upon request.


  1. 1.

    Humphries, M. D. & Prescott, T. J. The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog. Neurobiol. 90, 385–417 (2010).

    PubMed  Article  Google Scholar 

  2. 2.

    Castro, D. C. & Berridge, K. C. Opioid hedonic hotspot in nucleus accumbens shell: mu, delta, and kappa maps for enhancement of sweetness “liking” and “wanting”. J. Neurosci. 34, 4239–4250 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Kupchik, Y. M. et al. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections. Nat. Neurosci. 18, 1230–1232 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Creed, M., Ntamati, N. R., Chandra, R., Lobo, M. K. & Lüscher, C. Convergence of reinforcing and anhedonic cocaine effects in the ventral pallidum. Neuron 92, 214–226 (2016).

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Williams, D. J., Crossman, A. R. & Slater, P. The efferent projections of the nucleus accumbens in the rat. Brain Res. 130, 217–227 (1977).

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Krause, M., German, P. W., Taha, S. A. & Fields, H. L. A pause in nucleus accumbens neuron firing is required to initiate and maintain feeding. J. Neurosci. 30, 4746–4756 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    O’Connor, E. C. et al. Accumbal D1R neurons projecting to lateral hypothalamus authorize feeding. Neuron 88, 553–564 (2015).

    Article  CAS  Google Scholar 

  8. 8.

    Roitman, M. F., Wheeler, R. A. & Carelli, R. M. Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron 45, 587–597 (2005).

    CAS  Article  Google Scholar 

  9. 9.

    Faure, A., Richard, J. M. & Berridge, K. C. Desire and dread from the nucleus accumbens: cortical glutamate and subcortical GABA differentially generate motivation and hedonic impact in the rat. PLoS ONE 5, e11223 (2010).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  10. 10.

    Stratford, T. R. Activation of feeding-related neural circuitry after unilateral injections of muscimol into the nucleus accumbens shell. Brain Res. 1048, 241–250 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Brog, J. S., Salyapongse, A., Deutch, A. Y. & Zahm, D. S. 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, 255–278 (1993).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  12. 12.

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

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Spooren, W. P., Lynd-Balta, E., Mitchell, S. & Haber, S. N. Ventral pallidostriatal pathway in the monkey: evidence for modulation of basal ganglia circuits. J. Comp. Neurol. 370, 295–312 (1996).

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Mallet, N. et al. Dichotomous organization of the external globus pallidus. Neuron 74, 1075–1086 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Mallet, N. et al. Arkypallidal cells send a stop signal to striatum. Neuron 89, 308–316 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Glajch, K. E. et al. Npas1+ pallidal neurons target striatal projection neurons. J. Neurosci. 36, 5472–5488 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Ambroggi, F., Ghazizadeh, A., Nicola, S. M. & Fields, H. L. Roles of nucleus accumbens core and shell in incentive-cue responding and behavioral inhibition. J. Neurosci. 31, 6820–6830 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Richard, J. M., Ambroggi, F., Janak, P. H. & Fields, H. L. Ventral pallidum neurons encode incentive value and promote cue-elicited instrumental actions. Neuron 90, 1165–1173 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Ottenheimer, D., Richard, J. M. & Janak, P. H. Ventral pallidum encodes relative reward value earlier and more robustly than nucleus accumbens. Nat. Commun. 9, 4350 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  20. 20.

    Fujimoto, A. et al. Signaling incentive and drive in the primate ventral pallidum for motivational control of goal-directed action. J. Neurosci. 39, 1793–1804 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    White, J. K. et al. A neural network for information seeking. Nat. Commun. 10, 5168 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  22. 22.

    Cheer, J. F., Heien, M. L. A. V., Garris, P. A., Carelli, R. M. & Wightman, R. M. Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: implications for intracranial self-stimulation. Proc. Natl Acad. Sci. USA 102, 19150–19155 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Taha, S. A. & Fields, H. L. Encoding of palatability and appetitive behaviors by distinct neuronal populations in the nucleus accumbens. J. Neurosci. 25, 1193–1202 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Taha, S. A. & Fields, H. L. Inhibitions of nucleus accumbens neurons encode a gating signal for reward-directed behavior. J. Neurosci. 26, 217–222 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Roitman, M. F., Wheeler, R. A., Tiesinga, P. H. E., Roitman, J. D. & Carelli, R. M. Hedonic and nucleus accumbens neural responses to a natural reward are regulated by aversive conditioning. Learn. Mem. 17, 539–546 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Ledbetter, N. M., Chen, C. D. & Monosov, I. E. Multiple mechanisms for processing reward uncertainty in the primate basal forebrain. J. Neurosci. 36, 7852–7864 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Faget, L. et al. Opponent control of behavioral reinforcement by inhibitory and excitatory projections from the ventral pallidum. Nat. Commun. 9, 849 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  29. 29.

    Tooley, J. et al. Glutamatergic ventral pallidal neurons modulate activity of the habenula–tegmental circuitry and constrain reward seeking. Biol. Psychiatry 83, 1012–1023 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Berridge, K. C. Measuring hedonic impact in animals and infants: microstructure of affective taste reactivity patterns. Neurosci. Biobehav. Rev. 24, 173–198 (2000).

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Strickland, J. A., Austen, J. M. & Sanderson, D. J. A biphasic reduction in a measure of palatability following sucrose consumption in mice. Physiol. Behav. 184, 129–134 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Adamantidis, A. R. et al. Optogenetic interrogation of dopaminergic modulation of the multiple phases of reward-seeking behavior. J. Neurosci. 31, 10829–10835 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    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).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Chang, S. E., Todd, T. P. & Smith, K. S. Paradoxical accentuation of motivation following accumbens–pallidum disconnection. Neurobiol. Learn. Mem. 149, 39–45 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Peciña, S. & Berridge, K. C. Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness? J. Neurosci. 25, 11777–11786 (2005).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  37. 37.

    Brown, M. T. C. et al. Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning. Nature 492, 452–456 (2012).

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Collins, A. L. et al. Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior. Biol. Psychiatry 86, 388–396 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Reynolds, S. M. & Berridge, K. C. Glutamate motivational ensembles in nucleus accumbens: rostrocaudal shell gradients of fear and feeding. Eur. J. Neurosci. 17, 2187–2200 (2003).

    PubMed  Article  Google Scholar 

  40. 40.

    Reed, S. J. et al. Coordinated reductions in excitatory input to the nucleus accumbens underlie food consumption. Neuron 99, 1260–1273 (2018).

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Richard, J. M., Plawecki, A. M. & Berridge, K. C. Nucleus accumbens GABAergic inhibition generates intense eating and fear that resists environmental retuning and needs no local dopamine. Eur. J. Neurosci. 37, 1789–1802 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Van Bockstaele, E. J. & Pickel, V. M. GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain. Brain Res. 682, 215–221 (1995).

    PubMed  Article  Google Scholar 

  43. 43.

    Hurley, S. W. & Johnson, A. K. The role of the lateral hypothalamus and orexin in ingestive behavior: a model for the translation of past experience and sensed deficits into motivated behaviors. Front. Syst. Neurosci. 8, 216 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Wakabayashi, K. T. et al. Chemogenetic activation of ventral tegmental area GABA neurons, but not mesoaccumbal GABA terminals, disrupts responding to reward-predictive cues. Neuropsychopharmacology 44, 372–380 (2019).

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    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).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  46. 46.

    Jennings, J. H. et al. Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell 160, 516–527 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Marino, R. A. M. et al. Control of food approach and eating by a GABAergic projection from lateral hypothalamus to dorsal pons. Proc. Natl Acad. Sci. USA 117, 8611–8615 (2020).

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Root, D. H. et al. Slow phasic and tonic activity of ventral pallidal neurons during cocaine self-administration. Synapse 66, 106–127 (2012).

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Ottenheimer, D. J. et al. A quantitative reward prediction error signal in the ventral pallidum. Nat. Neurosci. 23, 1267–1276 (2020).

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Bocklisch, C. et al. Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. Science 341, 1521–1525 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  51. 51.

    Alpizar, S. A., Baker, A. L., Gulledge, A. T. & Hoppa, M. B. Loss of neurofascin-186 disrupts alignment of ankyrinG relative to its binding partners in the axon initial segment. Front. Cell. Neurosci. 13, 1 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Renier, N. et al. Mapping of brain activity by automated volume analysis of immediate early genes. Cell 165, 1789–1802 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Renier, N. et al. iDISCO: a simple, rapid method to immunolabel large tissue samples for volume imaging. Cell 159, 896–910 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  55. 55.

    Paxinos, G. & Franklin, B. J. F. The Mouse Brain in Stereotaxic Coordinates, Compact 5th edn (Academic Press, 2019).

  56. 56.

    Lopes, G. et al. Bonsai: an event-based framework for processing and controlling data streams. Front. Neuroinform. 9, 7 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Fobbs, W. C. et al. Continuous representations of speed by striatal medium spiny neurons. J. Neurosci. 40, 1679–1688 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  58. 58.

    Parker, L. A. Aversive taste reactivity: reactivity to quinine predicts aversive reactivity to lithium-paired sucrose solution. Pharmacol. Biochem. Behav. 47, 73–75 (1994).

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Nguyen, K. P. et al. Feeding Experimentation Device (FED): construction and validation of an open-source device for measuring food intake in rodents. J. Vis. Exp. (2017).

  60. 60.

    Nguyen, K. P., O’Neal, T. J., Bolonduro, O. A., White, E. & Kravitz, A. V. Feeding Experimentation Device (FED): a flexible open-source device for measuring feeding behavior. J. Neurosci. Methods 267, 108–114 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  61. 61.

    Godynyuk, E., Bluitt, M. N., Tooley, J. R., Kravitz, A. V. & Creed, M. C. An open-source, automated home-cage sipper device for monitoring liquid ingestive behavior in rodents. Eneuro (2019).

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We thank A. V. Kravitz for assistance with fiber photometery and in vivo electrophysiology experiments and M. C. Stander for excellent technical help. We thank A. V. Kravitz and I. Monosov for critical reading of the manuscript. Graphics used in schematics of experiments were adapted from Research was supported by intramural funds from the US National Institute of Child Health and Human Development (to C.E.L.P.) and internal funds from the McDonnell Center for Systems Neuroscience (to B.M.-A.) and Department of Anesthesiology at Washington University in St Louis (to M.C.C.), the Brain and Behavior Research Foundation (NARSAD Young Investigator Grant 27197 to M.C.C.), National Institutes of Health National Institute on Drug Abuse (R21-DA047127, R01-DA049924 to M.C.C.), a Whitehall Foundation Grant (2017-12-54 to M.C.C.) and a Rita Allen Scholar Award in Pain (to M.C.C.).

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Y.M.V., K.A. and M.C.C. wrote the paper with input from all authors. Y.M.V., J.R.T., L.M., L.M.R., H.S. and T.E. performed anatomical experiments. Y.M.V., K.A. and M.C.C. performed patch-clamp physiology. M.C.C., J.R.T. and O.U. performed in vivo electrophysiology. Y.M.V., J.R.T. and E.G. performed fiber photometry. Y.M.V., J.R.T., E.C. and K.A. performed behavioral experiments. B.M.-A. engineered custom hardware for behavioral experiments and B.M.-A. and T.E. developed the analytical methods. Data were analyzed by Y.M.V., J.R.T., K.A. and M.C.C. Work was supervised by B.M.-A., C.E.L.P. and M.C.C.

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Correspondence to Meaghan C. Creed.

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Peer review information Nature Neuroscience thanks Melissa Sharpe, Marcus Stephenson-Jones and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 NAcSh units are activated by reward approach.

a-b, Top: examples of approach-activated and approach-inhibited single units from the same mouse, aligned to drinking onset. Raster and PSTH of units activated and inhibited during reward approach; bottom = mean ± SEM. c, Summary of approach-related responses of n=32 multi-units from 6 mice; 6.25% decrease, 25.0% increase, 68.75% no change, and normalized firing rate changes in response to approach (mean increase = 1.81 ± 0.20, mean decrease = 0.79 ± 0.09; mean ± sem (d) Euler diagram showing overlap of functionally defined NAcSh units.

Extended Data Fig. 2 NAcSh inhibition promotes reward consumption without inducing a place preference or locomotor effects.

a, Histology showing viral infection and optic fiber placement (scale bar = 1 mm). b, Arch stimulation increased total drinking time (Arch No Stim: 217.93±21.57 sec, Arch Stim: 267.95±22.93 sec, t14 = 3.77, p = 0.002; eYFP No Stim: 24.422±30.03 sec, eYFP Stim: 231.43±25.55 sec, t7 =1.68, p=0.14), (c) number of bouts (Arch No Stim: 48.88±4.29, Arch Stim: 53.63±4.69 sec, t14 = 2.47, p = 0.038; eYFP No Stim: 43.21±5.40, eYFP Stim: 44.13±6.00, t7 =0.88, p=0.41) and (d) mean bout length (Arch No Stim: 4.63 ± 0.37 sec, Arch Stim: 5.16±0.46 sec, t14 = 2.27, p = 0.040; eYFP No Stim: 5.836 ± 0.847 sec, eYFP Stim:5.836±0.847, t7 =2.28, p = 0.06). (e) Arch3 inhibition did not induce a place preference in a RTPP task (eYFP: -11.92±7.71%, Arch: 1.06±5.96, t19=1.22, p=0.24) or (f) alter locomotor activity in an open field task (eYFP No Stim: 320.97±13.41 m, eYFP Stim: 323.41±12.02 m, Arch No Stim: 353.12±22.46 m, Arch Stim: 374.07±21.34 m, FStimxVirus;1,19=1.33, p=0.26). n=12/15, eYFP/Arch3). All data is represented as mean ± IQ range. *p<0.05, **p < 0.01.

Extended Data Fig. 3 Retrograde viral tracing reveals vArky fibers preferentially in the NAcSh.

(a) rAAV-Cre was injected in the NAcSh, DIO-ChR2 was injected into the VP and serial sections were taken of known VP projection sites. (b-c) 5x and 20x overview of ChR2-labeled terminals in the NAcSh and infected cell bodies in the VP (n=4 sections/brain region, 6 mice). (d) 10x representative images of serial sections (top) and 20x confocal images of canonical VP projection areas. (e) Quantification of total axonal length, normalized to VP. Intensity and axonal length in the NAcSh was significantly greater than any area examined. Abbreviations: Nucleus accumbens shell (NAcSh), ventral pallidum (VP), medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), basolateral amygdala (BLA) lateral habenula (LHb), mediodorsal thalamus (MDThal), subthalamic nucleus (STN), ventral tegmental area (VTA). F=148.4 p<0.001, Ffluorescence=148.4, p = 0.0016 with Bonferroni correction for multiple comparisons applied. Data presented as mean ± IQ range. Scale bars=25 µm.

Extended Data Fig. 4 Topography of release properties of VP inputs to NAcSh.

a, Merged fluorescent image of recorded tomato-expressing neuron adjacent to EYFP-labeled terminals from the VP during patch-clamp experiments. b, 4x image of ChR2-injection site in VP and terminal fields in the NAc in each of three reporter lines. Amplitude (c) and PPR (d) of oIPSC expressed as location of recorded neuron within the NAcSh in D1-MSNs (n=118 cells/11 mice), D2-MSNs (n=117 cells/12 mice), PVs (n=112 cells/12 mice), and CINs (n=104 cells/10 mice), scale bar = 50 µm.

Extended Data Fig. 5 Properties of NAcSh neurons and in vivo responses to activation of vArky terminals.

a, Location of recording arrays in the NAcSh. b–d, Units were classified according to peak-valley width (n = 9 pMSNs, 14 pINS, 32 multi-units from 6 mice, pMSN: 462.8±27.96 µs, pIN: 242.01±26.27 µs), CV (pMSN: 1.77±0.254, pIN: 1.23±0.17) and firing rate (pMSN: 0.40±0.11 Hz, pIN: 3.53±1.20 Hz, data shown as mean ± IQ range). e–h, representative waveform and PSTH of single neural examples in response to 15 ms of vArky stimulation. Scale bar = 500µs, 50µV.

Extended Data Fig. 6 Lick behavior of individual subjects, as a function of high- vs. low-vArky calcium signals.

a, Single-subject heat map of arkypallidal fluorescence signal across high GCaMP (top) and low GCaMP (bottom) trials aligned to reward consumption onset. b, Lick behavior of high- vs. low-vArky calcium trials of all individual GCaMP-injected subjects. c, Single-subject heat map of fluorescence signal of GFP mouse. d, Lick behavior of high- vs. low-VP signal trials of all GFP-injected subjects, (e) Average lick behavior of high and low-VP signal trials of all GFP-injected mice (AUC lick probability high signal trials: 3.16±0.65, AUC lick probability low signal trials: 2.94±0.49, mean ± IQ range).

Extended Data Fig. 7 Calcium activity in the NAcSh decreases upon reward consumption onset.

a-b, GCaMP injection in the NAcSh, representative traces (scale bar: 10 sec, 1 z-score) and histology (n=6/6 GCaMP/GFP mice, scale bar = 1 mm). c, Single-subject heat map of NAcSh GCaMP signal and (d) combined signal from all subjects (n=6/6 GCaMP/GFP) aligned to reward consumption onset (mean AUC GCaMP: -2.58±0.65, GFP: -0.14±1.40, t11=2.87, p=0.015, mean ± IQ range).

Extended Data Fig. 8 vArky calcium activity increases during sucrose pellet consumption but not locomotor events.

a, vArky fluorescence signal was recorded during free-access consumption of sucrose pellets. b, Representative heat map and normalized calcium signal aligned to sucrose pellet retrieval in GCaMP (left) and GFP (right) expressing mice. c, AUC was significantly greater in the two seconds following pellet retrieval in GCaMP-expressing mice relative to GFP controls (AUC GCAMP: 3.687 ± 0.756, AUC GFP: 0.238 ± 1.378, t16=2.1944, p=0.0433). d-f, Fluorescence responses aligned to locomotor arrests (mean AUC GCaMP: -1.467±0.2994, GFP: -0.3198±1.071, t16=1.127, p=0.27), locomotor initiations (n=704/677 events, AUC GCaMP: -0.818±0.638, GFP: -0.619±1.210, t16=0.150, p=0.88) and peaks in locomotor speed (n=1309/1221 events, mean AUC GCaMP: 0.1294±0.2945, GFP:0.4977±0.3022, t16=0.873, p=0.396). Data mean ± IQ range.

Extended Data Fig. 9 Histological verification, ICSS and RTPP behavioral controls for vArky optogenetic stimulation.

a, Infection site in VP and terminal fields in NAcSh; scale bar=50µm. b, Verified placements of optic fibers. c, Distance traveled in an open field task (n=12 eYFP, 18 ChR2, eYFPNoStim: 121.62±22.63, eYFPStim : 122.15±21.75, p=0.96, ChR2NoStim: 124.48±16.22, ChR2Stim: 121.83±14.18, Fstim•virus=0.050, p=0.825). d, Preference for the stimulation-paired side of a chamber in a real-time place preference task (n=12 eYFP, 18 ChR2, eYFP: -4.36±4.32%, ChR2: -1.13±5.83) and representative heatmaps. *p<0.05, **p<0.01. All data presented as mean ± sem.

Extended Data Fig. 10 Input-output curves of vArky neuronal responses to current injections ex vivo.

a, Ai14 reporter mice were injected with retro-cre in the NAcSh to selectively label vArky neurons. b, Merged fluorescent image of Ai14-expressing vArky neurons during patch-clamp experiments (n=12 neurons from 9 mice). c, The mean number of action potentials per second in response to successive current injection (0 to 200 pA) is plotted (error bars: sem). d, Representative traces in response to 50, 100, 150, and 200 pA current injections. Scale bar: 10mV, 100ms.

Supplementary information

Supplementary Information

Supplementary Figs. 1 and 2.

Reporting Summary

Supplementary Video 1

Example video of iDisco-processed and light sheet–imaged brain hemispheres. Retro-Cre was injected in the NAcSh and DIO-ChR2 was injected in the VP to visualize vArky neurons.

Supplementary Video 2

Example of orofacial taste reactivity test, with and without vArkypallidal stimulation.

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Vachez, Y.M., Tooley, J.R., Abiraman, K. et al. Ventral arkypallidal neurons inhibit accumbal firing to promote reward consumption. Nat Neurosci (2021).

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