Abstract
Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons exhibited low-latency responses to 'Stop' cues, irrespective of whether actions were canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) only responded to Stop cues in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral 'core' subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with stopping requiring Stop-cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aron, A.R. & Poldrack, R.A. Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. J. Neurosci. 26, 2424–2433 (2006).
Frank, M.J. Hold your horses: a dynamic computational role for the subthalamic nucleus in decision making. Neural Netw. 19, 1120–1136 (2006).
Logan, G.D., Cowan, W.B. & Davis, K.A. On the ability to inhibit simple and choice reaction time responses: a model and a method. J. Exp. Psychol. Hum. Percept. Perform. 10, 276–291 (1984).
Boucher, L., Palmeri, T.J., Logan, G.D. & Schall, J.D. Inhibitory control in mind and brain: an interactive race model of countermanding saccades. Psychol. Rev. 114, 376–397 (2007).
Robbins, T.W., Gillan, C.M., Smith, D.G., de Wit, S. & Ersche, K.D. Neurocognitive endophenotypes of impulsivity and compulsivity: towards dimensional psychiatry. Trends Cogn. Sci. 16, 81–91 (2012).
Eagle, D.M. et al. Stop-signal reaction-time task performance: role of prefrontal cortex and subthalamic nucleus. Cereb. Cortex 18, 178–188 (2008).
Hanes, D.P. & Schall, J.D. Neural control of voluntary movement initiation. Science 274, 427–430 (1996).
Osman, A., Kornblum, S. & Meyer, D.E. The point-of-no-return in choice reaction-time–controlled and ballistic stages of response preparation. J. Exp. Psychol. Hum. Percept. Perform. 12, 243–258 (1986).
Hikosaka, O. & Wurtz, R.H. Effects on eye-movements of a GABA agonist and antagonist injected into monkey superior colliculus. Brain Res. 272, 368–372 (1983).
Baunez, C. et al. Effects of STN lesions on simple vs choice reaction time tasks in the rat: preserved motor readiness, but impaired response selection. Eur. J. Neurosci. 13, 1609–1616 (2001).
Bergman, H., Wichmann, T. & DeLong, M.R. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249, 1436–1438 (1990).
Ballanger, B. et al. Stimulation of the subthalamic nucleus and impulsivity: release your horses. Ann. Neurol. 66, 817–824 (2009).
Majid, D.S., Cai, W., George, J.S., Verbruggen, F. & Aron, A.R. Transcranial magnetic stimulation reveals dissociable mechanisms for global versus selective corticomotor suppression underlying the stopping of action. Cereb. Cortex 22, 363–371 (2012).
Jahfari, S. et al. Effective connectivity reveals important roles for both the hyperdirect (fronto-subthalamic) and the indirect (fronto-striatal-pallidal) fronto-basal ganglia pathways during response inhibition. J. Neurosci. 31, 6891–6899 (2011).
Frank, M.J., Samanta, J., Moustafa, A.A. & Sherman, S.J. Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism. Science 318, 1309–1312 (2007).
Hikosaka, O. & Wurtz, R.H. Visual and oculomotor functions of monkey substantia nigra pars reticulata. I. Relation of visual and auditory responses to saccades. J. Neurophysiol. 49, 1230–1253 (1983).
Kravitz, A.V. et al. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466, 622–626 (2010).
Bevan, M.D., Bolam, J.P. & Crossman, A.R. Convergent synaptic input from the neostriatum and the subthalamus onto identified nigrothalamic neurons in the rat. Eur. J. Neurosci. 6, 320–334 (1994).
Aron, A.R. From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses. Biol. Psychiatry 69, e55–e68 (2011).
Gage, G.J., Stoetzner, C.R., Wiltschko, A.B. & Berke, J.D. Selective activation of striatal fast-spiking interneurons during choice execution. Neuron 67, 466–479 (2010).
Leventhal, D.L. et al. Basal ganglia beta oscillations accompany cue utilization. Neuron 73, 523–536 (2012).
Stuphorn, V., Brown, J.W. & Schall, J.D. Role of supplementary eye field in saccade initiation: executive, not direct, control. J. Neurophysiol. 103, 801–816 (2010).
Brown, J.W., Hanes, D.P., Schall, J.D. & Stuphorn, V. Relation of frontal eye field activity to saccade initiation during a countermanding task. Exp. Brain Res. 190, 135–151 (2008).
Cheruel, F., Dormont, J.F. & Farin, D. Activity of neurons of the subthalamic nucleus in relation to motor performance in the cat. Exp. Brain Res. 108, 206–220 (1996).
Deniau, J.M., Mailly, P., Maurice, N. & Charpier, S. The pars reticulata of the substantia nigra: a window to basal ganglia output. Prog. Brain Res. 160, 151–172 (2007).
Pare, M. & Hanes, D.P. Controlled movement processing: superior colliculus activity associated with countermanded saccades. J. Neurosci. 23, 6480–6489 (2003).
Handel, A. & Glimcher, P.W. Quantitative analysis of substantia nigra pars reticulata activity during a visually guided saccade task. J. Neurophysiol. 82, 3458–3475 (1999).
Schultz, W. Activity of pars reticulata neurons of monkey substantia-nigra in relation to motor, sensory, and complex events. J. Neurophysiol. 55, 660–677 (1986).
Basso, M.A. & Sommer, M.A. Exploring the role of the substantia nigra pars reticulata in eye movements. Neuroscience 198, 205–212 (2011).
Albin, R.L., Young, A.B. & Penney, J.B. The functional-anatomy of basal ganglia disorders. Trends Neurosci. 12, 366–375 (1989).
Lo, C.C. & Wang, X.J. Cortico-basal ganglia circuit mechanism for a decision threshold in reaction time tasks. Nat. Neurosci. 9, 956–963 (2006).
Humphries, M.D. & Gurney, K.N. A pulsed neural network model of bursting in the basal ganglia. Neural Netw. 14, 845–863 (2001).
Humphries, M.D., Stewart, R.D. & Gurney, K.N. A physiologically plausible model of action selection and oscillatory activity in the basal ganglia. J. Neurosci. 26, 12921–12942 (2006).
Blomfield, S. Arithmetical operations performed by nerve cells. Brain Res. 69, 115–124 (1974).
Segev, I. Dendritic processing. in The Handbook of Brain Theory and Neural Networks. (ed. Arbib, M.A.) 282–289 (MIT Press, 1998).
Sharp, D.J. et al. Distinct frontal systems for response inhibition, attentional capture, and error processing. Proc. Natl. Acad. Sci. USA 107, 6106–6111 (2010).
Shulman, G.L. et al. Interaction of stimulus-driven reorienting and expectation in ventral and dorsal frontoparietal and basal ganglia-cortical networks. J. Neurosci. 29, 4392–4407 (2009).
Levy, B.J. & Wagner, A.D. Cognitive control and right ventrolateral prefrontal cortex: reflexive reorienting, motor inhibition, and action updating. Ann. NY Acad. Sci. 1224, 40–62 (2011).
Wiecki, T.V. & Frank, M.J. A computational model of inhibitory control in frontal cortex and basal ganglia. Psychol. Rev. 120, 329–355 (2013).
Matsumoto, N., Minamimoto, T., Graybiel, A.M. & Kimura, M. Neurons in the thalamic CM-Pf complex supply striatal neurons with information about behaviorally significant sensory events. J. Neurophysiol. 85, 960–976 (2001).
Pan, W.X. & Hyland, B.I. Pedunculopontine tegmental nucleus controls conditioned responses of midbrain dopamine neurons in behaving rats. J. Neurosci. 25, 4725–4732 (2005).
Deschenes, M., Bourassa, J., Doan, V.D. & Parent, A. A single-cell study of the axonal projections arising from the posterior intralaminar thalamic nuclei in the rat. Eur. J. Neurosci. 8, 329–343 (1996).
Kita, T. & Kita, H. Cholinergic and non-cholinergic mesopontine tegmental neurons projecting to the subthalamic nucleus in the rat. Eur. J. Neurosci. 33, 433–443 (2011).
Kimura, M., Minamimoto, T., Matsumoto, N. & Hori, Y. Monitoring and switching of cortico-basal ganglia loop functions by the thalamo-striatal system. Neurosci. Res. 48, 355–360 (2004).
McHaffie, J.G., Stanford, T.R., Stein, B.E., Coizet, W. & Redgrave, P. Subcortical loops through the basal ganglia. Trends Neurosci. 28, 401–407 (2005).
Ding, J.B., Guzman, J.N., Peterson, J.D., Goldberg, J.A. & Surmeier, D.J. Thalamic gating of corticostriatal signaling by cholinergic interneurons. Neuron 67, 294–307 (2010).
Cavanagh, J.F. et al. Subthalamic nucleus stimulation reverses mediofrontal influence over decision threshold. Nat. Neurosci. 14, 1462–1467 (2011).
Watanabe, M. & Munoz, D.P. Neural correlates of conflict resolution between automatic and volitional actions by basal ganglia. Eur. J. Neurosci. 30, 2165–2176 (2009).
Cui, G. et al. Concurrent activation of striatal direct and indirect pathways during action initiation. Nature 494, 238–242 (2013).
Zandbelt, B.B. & Vink, M. On the role of the striatum in response inhibition. PLoS ONE 5, e13848 (2010).
Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates 5th edn. (Elsevier Academic Press, 2005).
Wiltschko, A.B., Gage, G.J. & Berke, J.D. Wavelet filtering before spike detection preserves waveform shape and enhances single-unit discrimination. J. Neurosci. Methods 173, 34–40 (2008).
Berke, J.D. Uncoordinated firing rate changes of striatal fast-spiking interneurons during behavioral task performance. J. Neurosci. 28, 10075–10080 (2008).
Verbruggen, F. & Logan, G.D. Models of response inhibition in the stop-signal and stop-change paradigms. Neurosci. Biobehav. Rev. 33, 647–661 (2009).
Gerstner, W. & Kistler, W.M. Spiking Neuron Models (Cambridge University Press, 2002).
Connelly, W.M., Schulz, J.M., Lees, G. & Reynolds, J.N.J. Differential short-term plasticity at convergent inhibitory synapses to the substantia nigra pars reticulata. J. Neurosci. 30, 14854–14861 (2010).
Acknowledgements
We thank V. Stuphorn, D. Weissman, A. Aron, G. Morris, M. Churchland, M. Bevan and D. Meyer for their helpful comments. J. Pettibone and A. Case provided valuable assistance. This work was supported by Deutsche Forschungsgemeinschaft grant SCHM 2745/1-1, the US National Institute on Drug Abuse, National Institute on Neurological Disorders and Stroke, and the University of Michigan.
Author information
Authors and Affiliations
Contributions
J.D.B. designed and oversaw the project. D.K.L. helped develop the behavioral task. D.K.L., N.M. and F.C. performed electrophysiological experiments. R.S. developed and performed the data analyses and computational modeling. R.S. and J.D.B. wrote the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Figures and Text
Supplementary Figures 1–10 and Supplementary Table 1 (PDF 14373 kb)
Supplementary Video 1
Video recording of a rat performing Go and Stop trials (MOV 3332 kb)
Rights and permissions
About this article
Cite this article
Schmidt, R., Leventhal, D., Mallet, N. et al. Canceling actions involves a race between basal ganglia pathways. Nat Neurosci 16, 1118–1124 (2013). https://doi.org/10.1038/nn.3456
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.3456
This article is cited by
-
Sex differences in learning and performing the Go/NoGo tasks
Biology of Sex Differences (2023)
-
Cell and circuit complexity of the external globus pallidus
Nature Neuroscience (2023)
-
Pedunculopontine Chx10+ neurons control global motor arrest in mice
Nature Neuroscience (2023)
-
Optogenetic inhibition of indirect pathway neurons in the dorsomedial striatum reduces excessive grooming in Sapap3-knockout mice
Neuropsychopharmacology (2022)
-
Compromised reactive but intact proactive inhibitory motor control in Tourette disorder
Scientific Reports (2022)