Abstract
Synapses and receptive fields of the cerebral cortex are plastic. However, changes to specific inputs must be coordinated within neural networks to ensure that excitability and feature selectivity are appropriately configured for perception of the sensory environment. We induced long-lasting enhancements and decrements to excitatory synaptic strength in rat primary auditory cortex by pairing acoustic stimuli with activation of the nucleus basalis neuromodulatory system. Here we report that these synaptic modifications were approximately balanced across individual receptive fields, conserving mean excitation while reducing overall response variability. Decreased response variability should increase detection and recognition of near-threshold or previously imperceptible stimuli. We confirmed both of these hypotheses in behaving animals. Thus, modification of cortical inputs leads to wide-scale synaptic changes, which are related to improved sensory perception and enhanced behavioral performance.
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
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hubel, D.H. & Wiesel, T.N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. 160, 106–154 (1962).
Hirsch, J.A. & Martinez, L.M. Circuits that build visual cortical receptive fields. Trends Neurosci. 29, 30–39 (2006).
Huberman, A.D., Feller, M.B. & Chapman, B. Mechanisms underlying development of visual maps and receptive fields. Annu. Rev. Neurosci. 31, 479–509 (2008).
Ye, C.Q., Poo, M.M., Dan, Y. & Zhang, X.H. Synaptic mechanisms of direction selectivity in primary auditory cortex. J. Neurosci. 30, 1861–1868 (2010).
Frégnac, Y., Shulz, D., Thorpe, S. & Bienenstock, E. A cellular analogue of visual cortical plasticity. Nature 333, 367–370 (1988).
Talwar, S.K. & Gerstein, G.L. Reorganization in awake rat auditory cortex by local microstimulation and its effect on frequency-discrimination behavior. J. Neurophysiol. 86, 1555–1572 (2001).
Meliza, C.D. & Dan, Y. Receptive-field modification in rat visual cortex induced by paired visual stimulation and single-cell spiking. Neuron 49, 183–189 (2006).
Jacob, V., Brasier, D.J., Erchova, I., Feldman, D. & Shulz, D.E. Spike timing-dependent synaptic depression in the in vivo barrel cortex of the rat. J. Neurosci. 27, 1271–1284 (2007).
Katz, L.C. & Shatz, C.J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996).
Buonomano, D.V. & Merzenich, M.M. Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998).
Smith, G.B., Heynen, A.J. & Bear, M.F. Bidirectional synaptic mechanisms of ocular dominance plasticity in visual cortex. Phil. Trans. R. Soc. Lond. B 364, 357–367 (2009).
Fritz, J., Shamma, S., Elhilali, M. & Klein, D. Rapid task-related plasticity of spectrotemporal receptive fields in primary auditory cortex. Nat. Neurosci. 6, 1216–1223 (2003).
Feldman, D.E. & Brecht, M. Map plasticity in somatosensory cortex. Science 310, 810–815 (2005).
Dan, Y. & Poo, M.M. Spike timing-dependent plasticity: from synapse to perception. Physiol. Rev. 86, 1033–1048 (2006).
de Villers-Sidani, E., Chang, E.F., Bao, S. & Merzenich, M.M. Critical period window for spectral tuning defined in the primary auditory cortex (A1) of the rat. J. Neurosci. 27, 180–189 (2007).
Li, Y., Van Hooser, S.D., Mazurek, M., White, L.E. & Fitzpatrick, D. Experience with moving visual stimuli drives the early development of cortical direction selectivity. Nature 456, 952–956 (2008).
Dorrn, A.L., Yuan, K., Barker, A.J., Schreiner, C.E. & Froemke, R.C. Developmental sensory experience balances cortical excitation and inhibition. Nature 465, 932–936 (2010).
Dahmen, J.C., Hartley, D.E. & King, A.J. Stimulus-timing-dependent plasticity of cortical frequency representation. J. Neurosci. 28, 13629–13639 (2008).
Greuel, J.M., Luhmann, H.J. & Singer, W. Pharmacological induction of use-dependent receptive field modifications in the visual cortex. Science 242, 74–77 (1988).
Metherate, R. & Ashe, J.H. Nucleus basalis stimulation facilitates thalamocortical synaptic transmission in the rat auditory cortex. Synapse 14, 132–143 (1993).
Bakin, J.S. & Weinberger, N.M. Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis. Proc. Natl. Acad. Sci. USA 93, 11219–11224 (1996).
Froemke, R.C., Merzenich, M.M. & Schreiner, C.E. A synaptic memory trace for cortical receptive field plasticity. Nature 450, 425–429 (2007).
Goard, M. & Dan, Y. Basal forebrain activation enhances cortical coding of natural scenes. Nat. Neurosci. 12, 1444–1449 (2009).
Reed, A. et al. Cortical map plasticity improves learning but is not necessary for improved performance. Neuron 70, 121–131 (2011).
Fritz, J., Elhilali, M. & Shamma, S. Active listening: task-dependent plasticity of spectrotemporal receptive fields in primary auditory cortex. Hear. Res. 206, 159–176 (2005).
Shuler, M.G. & Bear, M.F. Reward timing in the primary visual cortex. Science 311, 1606–1609 (2006).
Martin, S.J., Grimwood, P.D. & Morris, R.G.M. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000).
Hübener, M. & Bonhoeffer, T. Searching for engrams. Neuron 67, 363–371 (2010).
Brown, M., Irvine, D.R. & Park, V.N. Perceptual learning on an auditory frequency discrimination task by cats: association with changes in primary auditory cortex. Cereb. Cortex 14, 952–965 (2004).
Edeline, J.-M. & Weinberger, N.M. Receptive field plasticity in the auditory cortex during frequency discrimination training: selective retuning independent of task difficulty. Behav. Neurosci. 107, 82–103 (1993).
McLin, D.E. III, Miasnikov, A.A. & Weinberger, N.M. Induction of behavioral associative memory by stimulation of the nucleus basalis. Proc. Natl. Acad. Sci. USA 99, 4002–4007 (2002).
Han, Y.K., Köver, H., Insanally, M.N., Semerdijan, J.H. & Bao, S. Early experience impairs perceptual discrimination. Nat. Neurosci. 10, 1191–1197 (2007).
Abbott, L.F. & Nelson, S.B. Synaptic plasticity: taming the beast. Nat. Neurosci. 3, 1178–1183 (2000).
Toyoizumi, T. & Miller, K.D. Equalization of ocular dominance columns induced by an activity-dependent learning rule and the maturation of inhibition. J. Neurosci. 29, 6514–6525 (2009).
Desai, N.S., Cudmore, R.H., Nelson, S.B. & Turrigiano, G.G. Critical periods for experience-dependent synaptic scaling in visual cortex. Nat. Neurosci. 5, 783–789 (2002).
Royer, S. & Paré, D. Conservation of total synaptic weight through balanced synaptic potentiation and depression. Nature 422, 518–522 (2003).
Rumsey, C.C. & Abbott, L.F. Equalization of synaptic efficacy by activity- and timing-dependent synaptic plasticity. J. Neurophysiol. 91, 2273–2280 (2004).
Deweese, M.R. & Zador, A.M. Shared and private variability in the auditory cortex. J. Neurophysiol. 92, 1840–1855 (2004).
Lee, M.G., Hassani, O.K., Alonso, A. & Jones, B.E. Cholinergic basal forebrain neurons burst with theta during waking and paradoxical sleep. J. Neurosci. 25, 4365–4369 (2005).
Hasselmo, M.E. & Sarter, M. Modes and models of forebrain cholinergic neuromodulation of cognition. Neuropsychopharmacology 36, 52–73 (2011).
Zaborszky, L., Pang, K., Somogyi, J., Nadasdy, Z. & Kallo, I. The basal forebrain corticopetal system revisited. Ann. NY Acad. Sci. 877, 339–367 (1999).
Lin, S.C. & Nicolelis, M.A. Neuronal ensemble bursting in the basal forebrain encodes salience irrespective of valence. Neuron 59, 138–149 (2008).
Fries, P., Reynolds, J.H., Rorie, A.E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560–1563 (2001).
Averbeck, B.B., Latham, P.E. & Pouget, A. Neural correlations, population coding and computation. Nat. Rev. Neurosci. 7, 358–366 (2006).
Cohen, M.R. & Maunsell, J.H. Attention improves performance primarily by reducing interneuronal correlations. Nat. Neurosci. 12, 1594–1600 (2009).
Elhilali, M., Fritz, J.B., Chi, T.S. & Shamma, S. Auditory cortical receptive fields: stable entities with plastic abilities. J. Neurosci. 27, 10372–10382 (2007).
Tanner, W.P. & Swets, J.A. A decision-making theory of visual detection. Psychol. Rev. 61, 401–409 (1954).
Liu, R.C. & Schreiner, C.E. Auditory cortical detection and discrimination correlates with communicative significance. PLoS Biol. 5, e173 (2007).
Polley, D.B., Heiser, M.A., Blake, D.T., Schreiner, C.E. & Merzenich, M.M. Associative learning shapes the neural code for stimulus magnitude in primary auditory cortex. Proc. Natl. Acad. Sci. USA 101, 16351–16356 (2004).
Wright, B.A., Sabin, A.T., Zhang, Y., Marrone, N. & Fitzgerald, M.B. Enhancing perceptual learning by combining practice with periods of additional sensory stimulation. J. Neurosci. 30, 12868–12877 (2010).
Acknowledgements
We thank L.F. Abbott, T. Babcock, M. Berry, E. Chang, Z. Chen, E. de Villers-Sidani, A.L. Dorrn, P. Dutta, A. Fairhall, S.P. Gandhi, G. Glassner, C.A. Hoeffer, K. Imaizumi, B.J. Jones, N. Kopell, R. Liu, G. Myers, P. O'Hara, J. Shih, A.Y. Tan, C.-L. Teng and L. Wilbrecht for comments, discussions and technical assistance. J. Pivkova created the artwork in Figure 1a. This work was supported by the US National Institute on Deafness and Other Communication Disorders (grant DC009635 to R.C.F., grant DC009836 to D.B.P. and grant DC02260 to C.E.S.), US National Science Foundation (grants 0615308 and 0627126 to P.A.L.), Intel Research (P.A.L.), DoCoMo Capital and Foundation Capital (P.A.L.), the Conte Center for Neuroscience Research at the University of California, San Francisco (grant MH077970 to M.M.M. and C.E.S.), Hearing Research Inc. (C.E.S.), the John C. and Edward Coleman Fund (M.M.M. and C.E.S.) and the US National Academies Keck Future Initiatives (R.C.F. and P.A.L.). A.J.B. is supported by a US National Science Foundation Predoctoral Fellowship. M.W. is supported by a Sequoia Capital Stanford Graduate Fellowship. I.C. is supported by an US National Institute of Mental Health training grant. P.A.L. is supported by a Microsoft Research New Faculty Fellowship. R.C.F. is supported by a Sloan Research Fellowship.
Author information
Authors and Affiliations
Contributions
R.C.F., I.C., D.B.P., M.M.M. and C.E.S. designed the experiments. R.C.F., I.C. and A.R.O.M. performed the electrophysiological experiments. R.C.F., I.C., A.J.B., K.Y., B.A.S., N.Z. and H.B. performed the behavioral experiments. M.W. and P.A.L. designed and built the wireless device. R.C.F. wrote the manuscript. All authors discussed the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–10 (PDF 423 kb)
Rights and permissions
About this article
Cite this article
Froemke, R., Carcea, I., Barker, A. et al. Long-term modification of cortical synapses improves sensory perception. Nat Neurosci 16, 79–88 (2013). https://doi.org/10.1038/nn.3274
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.3274
This article is cited by
-
The cholinergic basal forebrain provides a parallel channel for state-dependent sensory signaling to auditory cortex
Nature Neuroscience (2023)
-
Dendrites help mitigate the plasticity-stability dilemma
Scientific Reports (2023)
-
Locus coeruleus activity improves cochlear implant performance
Nature (2023)
-
Effect of cortical extracellular GABA on motor response
Journal of Computational Neuroscience (2022)
-
Fear learning induces α7-nicotinic acetylcholine receptor-mediated astrocytic responsiveness that is required for memory persistence
Nature Neuroscience (2021)