Journal of Computational Neuroscience

, Volume 47, Issue 2–3, pp 191–204 | Cite as

Reducing variability in motor cortex activity at a resting state by extracellular GABA for reliable perceptual decision-making

  • Osamu HoshinoEmail author
  • Rikiya Kameno
  • Kazuo Watanabe


Interaction between sensory and motor cortices is crucial for perceptual decision-making, in which intracortical inhibition might have an important role. We simulated a neural network model consisting of a sensory network (NS) and a motor network (NM) to elucidate the significance of their interaction in perceptual decision-making in association with the level of GABA in extracellular space: extracellular GABA concentration. Extracellular GABA molecules acted on extrasynaptic receptors embedded in membranes of pyramidal cells and suppressed them. A reduction in extracellular GABA concentration either in NS or NM increased the rate of errors in perceptual decision-making, for which an increase in ongoing-spontaneous fluctuations in subthreshold neuronal activity in NM prior to sensory stimulation was responsible. Feedback (NM-to-NS) signaling enhanced selective neuronal responses in NS, which in turn increased stimulus-evoked neuronal activity in NM. We suggest that GABA in extracellular space contributes to reducing variability in motor cortex activity at a resting state and thereby the motor cortex can respond correctly to a subsequent sensory stimulus. Feedback signaling from the motor cortex improves the selective responsiveness of the sensory cortex, which ensures the fidelity of information transmission to the motor cortex, leading to reliable perceptual decision-making.


Sensory cortex Motor cortex Sensory perception Cortical GABA 


Compliance with Ethical Standards

Conflict of interests

The authors declare that they have no conflict of interest.


  1. Bianchim, M.T., Haas, K.F., Macdonald, R.L. (2001). Structural determinants of fast desensitization and desensitization-deactivation coupling in GABAa receptors. J. Neurosci., 21, 1127–36.Google Scholar
  2. Bianchim, M.T., Haas, K.F., Macdonald, R.L. (2002). Alpha1 and alpha6 subunits specify distinct desensitization, deactivation and neurosteroid modulation of GABA(A) receptors containing the delta subunit. Neuropharmacology, 43, 492–502.Google Scholar
  3. Brickley, S.G., Cull-Candy, S.G., Farrant, M. (1996). Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J. Physiol., 497.3, 753–759.Google Scholar
  4. Brown, N., Kerby, J., Bonnert, T.P., Whiting, P.J., Wafford, K.A. (2002). Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors. Br. J. Pharmacol., 136, 965–974.PubMedPubMedCentralGoogle Scholar
  5. deCharms, R.C., & Zador, A. (2000). Neural representation and the cortical code. Annu. Rev. Neurosci., 23, 613–647.PubMedGoogle Scholar
  6. Drasbek, K.R., & Jensen, K. (2006). THIP, a hypnotic and antinociceptive drug, enhances an extrasynaptic GABAA receptor-mediated conductance in mouse neocortex. Cereb. Cortex, 16, 1134–1141.PubMedGoogle Scholar
  7. Edden, R.A., Muthukumaraswamy, S.D., Freeman, T.C., Singh, K.D. (2009). Orientation discrimination performance is predicted by GABA concentration and gamma oscillation frequency in human primary visual cortex. J. Neurosci., 29, 15721–15726.PubMedPubMedCentralGoogle Scholar
  8. Farrant, M., & Nusser, Z. (2005). Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat. Rev. Neurosci., 6, 215–229.Google Scholar
  9. Fox, M.D., Snyder, A.Z., Vincent, J.L., Raichle, M.E. (2007). Intrinsic fluctuations within cortical systems account for intertrial variability in human behavior. Neuron, 56, 171–184.PubMedGoogle Scholar
  10. Gonzalez-Burgos, G., Fish, K.N., Lewis, D.A. (2011). GABA Neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia. Neural Plasticity, 2011, 723184.PubMedPubMedCentralGoogle Scholar
  11. Hasler, G., van der Veen, J.W., Tumonis, T., Meyers, N., Shen, J., Drevets, W.C. (2007). Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch. Gen. Psychiatry, 64, 193–200.PubMedGoogle Scholar
  12. Hatsopoulos, N.G., & Suminski, A.J. (2011). Sensing with the motor cortex. Neuron, 72, 477–487.PubMedPubMedCentralGoogle Scholar
  13. Hoshino, O. (2009). GABA Transporter preserving ongoing spontaneous neuronal activity at firing subthreshold. Neural Comput., 21, 1683–1713.Google Scholar
  14. Hoshino, O. (2012). Regulation of ambient GABA levels by neuron-glia signaling for reliable perception of multisensory events. Neural Comput., 24, 2964–2993.PubMedGoogle Scholar
  15. Hoshino, O. (2014). Balanced crossmodal excitation and inhibition essential for maximizing multisensory gain. Neural Comput., 26, 1362–1385.PubMedGoogle Scholar
  16. Hoshino, O., Zheng, M., Watanabe, K. (2018). Perceptual judgments via sensory-motor interaction assisted by cortical GABA. J. Comput. Neurosci., 44, 233–251.PubMedGoogle Scholar
  17. Jones, M.V., & Westbrook, G.L. (1995). Desensitized states prolong GABAA channel responses to brief agonist pulses. Neuron, 15, 181–91.PubMedGoogle Scholar
  18. Kolasinski, J., Logan, J.P., Hinson, E.L., Manners, D., Divanbeighi, Z.A.P., Makin, T.R., Emir, U.E., Stagg, C.J. (2017). A mechanistic link from GABA to cortical architecture and perception. Current Biology, 27, 1685–1691.PubMedCentralGoogle Scholar
  19. Lerma, J., Herranz, A.S., Herreras, O., Abraira, V., Martin, D.R. (1986). In vivo determination of extracellular concentration of amino acids in the rat hippocampus: A method based on brain dialysis and computerized analysis. Brain Res., 384, 145–155.PubMedGoogle Scholar
  20. Leventhal, A.G., Thompson, K.G., Liu, D., Zhou, Y., Ault, S.J. (1995). Concomitant sensitivity to orientation, direction, and color of cells in layers 2, 3, and 4 of monkey striate cortex. J. Neurosci., 15, 1808–1818.PubMedPubMedCentralGoogle Scholar
  21. Maconochie, D.J., Zempel, J.M., Steinbach, J.H. (1994). How quickly can GABAA receptors open?. Neuron, 12, 61–71.PubMedGoogle Scholar
  22. Makino, H., Hwang, E.J., Hedrick, N.G., Komiyama, T. (2016). Circuit Mechanisms of Sensorimotor Learning. Neuron, 92, 705–721.PubMedPubMedCentralGoogle Scholar
  23. Manita, S., Suzuki, T., Homma, C., Matsumoto, T., Odagawa, M., Yamada, K., Ota, K., Matsubara, V., Inutsuka, A., Sato, M., Ohkura, M., Yamanaka, A., Yanagawa, Y., Nakai, J., Hayashi, Y., Larkum, M.E., Murayama, M. (2015). A Top-Down Cortical Circuit for Accurate Sensory Perception. Neuron, 86, 1304–1316.PubMedGoogle Scholar
  24. Mao, T., Kusefoglu, D., Hooks, B.M., Huber, D., Petreanu, L., Svoboda, K. (2011). Long-range neuronal circuits underlying the interaction betweeN Ssory and motor cortex. Neuron, 72, 111–123.PubMedPubMedCentralGoogle Scholar
  25. Matyas, F., Sreenivasan, V., Marbach, F., Wacongne, C., Barsy, B., Mateo, C., Aronoff, R., Petersen, C.C. (2010). Motor control by sensory cortex. Science, 330, 1240–1243.PubMedGoogle Scholar
  26. Mountcastle, V.B. (1997). The columnar organization of the neocortex. Brain: A Journal of Neurology, 120, 701–722.Google Scholar
  27. Nusser, Z., Roberts, J.D., Baude, A., Richards, J.G., Somogyi, P. (1995). Relative densities of synaptic and extrasynaptic GABAA receptors on cerebellar granule cells as determined by a quantitative immunogold method. The Journal of Neuroscience, 5, 2948–2960.Google Scholar
  28. Ortinski, P.I., Turner, J.R., Barberis, A., Motamedi, G., Yasuda, R.P., Wolfe, B.B., Kellar, K.J., Vicini, S. (2006). Deletion of the GABA(a) receptor alpha1 subunit increases tonic GABA(a) receptor current: a role for GABA uptake transporters. The Journal of Neuroscience, 26, 9323–9331.PubMedPubMedCentralGoogle Scholar
  29. Puts, N.A., Edden, R.A., Evans, C.J., McGlone, F., McGonigle, D.J. (2011). Regionally specific human GABA concentration correlates with tactile discrimination thresholds. J. Neurosci., 31, 16556–16560.PubMedPubMedCentralGoogle Scholar
  30. Sachidhanandam, S., Sreenivasan, V., Kyriakatos, A., Kremer, Y., Petersen, C.C. (2013). Membrane potential correlates of sensory perception in mouse barrel cortex. Nature Neuroscience, 16, 1671–1677.PubMedGoogle Scholar
  31. Sandberg, K., Blicher, J.U., Dong, M.Y., Rees, G., Near, J., Kanai, R. (2014). Occipital GABA correlates with cognitive failures in daily life. Neuroimage, 87, 55–60.PubMedPubMedCentralGoogle Scholar
  32. Saxena, N.C., & Macdonald, R.L. (1996). Properties of putative cerebellar gamma-aminobutyric acidA receptor isoforms. Mol. Pharmacol., 49, 567–579.PubMedGoogle Scholar
  33. Schmolesky, M.T., Wang, Y., Pu, M., Leventhal, A.G. (2000). Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys. Nat. Neurosci., 3, 384–390.PubMedGoogle Scholar
  34. Scimemi, A., Semyanov, A., Sperk, G., Kullmann, D.M., Walker, M.C. (2005). Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J. Neurosci., 25, 10016–10024.PubMedPubMedCentralGoogle Scholar
  35. Scimemi, A., Andersson, A., Heeroma, J.H., Strandberg, J., Rydenhag, B., McEvoy, A.W., Thom, M., Asztely, F., Walker. M.C. (2006). Tonic GABA(A) receptor-mediated currents in human brain. Eur. J. Neurosci., 24, 1157–1160.PubMedGoogle Scholar
  36. Semyanov, A., Walker, M.C., Kullmann, D.M., Silver, R.A. (2004). Tonically active GABA A receptors: modulating gain and maintaining the tone. Trends Neurosci., 27, 262–269.PubMedGoogle Scholar
  37. Siddoway, B., Hou, H., Xia, H. (2014). Molecular mechanisms of homeostatic synaptic downscaling. Neuropharmacology, 78, 38–44.PubMedGoogle Scholar
  38. Soltesz, I., & Nusser, Z. (2001). Neurobiology. Background inhibition to the fore. Nature, 409, 24–25.Google Scholar
  39. Somogyi, P., Takagi, H., Richards, J.G., Mohler, H. (1989). Subcellular localization of benzodiazepine/GABAA receptors in the cerebellum of rat, cat, and monkey using monoclonal antibodies. J. Neurosci., 9, 2197–2209.PubMedPubMedCentralGoogle Scholar
  40. Stagg, C.J., Bestmann, S., Constantinescu, A.O., Moreno, L.M., Allman, C., Mekle, R., Woolrich, M., Near, J., Johan-Berg, H., Rothwell, J.C. (2011). Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex. J. Physiol., 589, 5845–5855.PubMedPubMedCentralGoogle Scholar
  41. Sumner, P., Edden, R.A., Bompas, A., Evans, C.J., Singh, K.D. (2010). More GABA, less distraction: a neurochemical predictor of motor decision speed. Nat. Neurosci., 13, 825–827.PubMedGoogle Scholar
  42. Tossman, U., Jonsson, G., Ungerstedt, U. (1986). Regional distribution and extracellular levels of amino acids in rat central nervous system. Acta Physiol. Scand., 127, 533–545.PubMedGoogle Scholar
  43. Turrigiano, G.G., & Nelson, S.B. (2000). Hebb and homeostasis in neuronal plasticity. Curr. Opin. Neurobiol., 10, 358–364.PubMedGoogle Scholar
  44. Xu, X., Ichida, J., Shostak, Y., Bonds, A.B., Casagrande, V.A. (2002). Are primate lateral geniculate nucleus (LGN) cells really sensitive to orientation or direction?. Vis. Neurosci., 19, 97–108.PubMedGoogle Scholar
  45. Zach, N., Inbar, D., Grinvald, Y., Bergman, H., Vaadia, E. (2008). Emergence of novel representations in primary motor cortex and premotor neurons during associative learning. J. Neurosci., 28, 9545–9556.PubMedPubMedCentralGoogle Scholar
  46. Zagha, E., Casale, A.E., Sachdev, R.N., McGinley, M.J., McCormick, D.A. (2013). Motor cortex feedback influences sensory processing by modulating network state. Neuron, 79, 567–578.PubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Intelligent Systems EngineeringIbaraki UniversityHitachiJapan
  2. 2.Southern Tohoku Research Institute for NeuroscienceSouthern Tohoku General HospitalKoriyamaJapan

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