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Emergence of cortical inhibition by coordinated sensory-driven plasticity at distinct synaptic loci

Nature Neuroscience volume 13, pages 1240–1248 (2010)Cite this article

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Abstract

Feedforward GABAergic inhibition sets the dendritic integration window, thereby controlling timing and output in cortical circuits. However, the manner in which feedforward inhibitory circuits emerge is unclear, despite this being a critical step for neocortical development and function. We found that sensory experience drove plasticity of the feedforward inhibitory circuit in mouse layer 4 somatosensory barrel cortex in the second postnatal week via two distinct mechanisms. First, sensory experience selectively strengthened thalamocortical-to-feedforward interneuron inputs via a presynaptic mechanism but did not regulate other inhibitory circuit components. Second, experience drove a postsynaptic mechanism in which a downregulation of a prominent thalamocortical NMDA excitatory postsynaptic potential in stellate cells regulated the final expression of functional feedforward inhibitory input. Thus, experience is required for specific, coordinated changes at thalamocortical synapses onto both inhibitory and excitatory neurons, producing a circuit plasticity that results in maturation of functional feedforward inhibition in layer 4.

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Figure 1: Sensory experience drives the developmental increase in feedforward inhibitory input in layer 4 barrel cortex.
Figure 2: Sensory experience drives an increase in the relative strength of thalamocortical synaptic transmission onto feedforward inhibitory interneurons.
Figure 3: Sensory experience causes a decrease in failure rate and alters paired-pulse plasticity at thalamocortical synapses onto feedforward inhibitory interneurons.
Figure 4: Sensory experience does not alter synaptic transmission or connectivity between feedforward interneurons and stellate cells in layer 4.
Figure 5: Lack of effective feedforward inhibition in a subpopulation of stellate cells despite the presence of a relatively large feedforward inhibitory input.
Figure 6: An NMDA receptor–mediated component to the thalamocortical synaptic response is prominent at resting membrane potential in P6–8 stellate cells and is developmentally downregulated.
Figure 7: The prominent thalamocortical NMDA component prolongs the PSP to offset the effects of feedforward inhibition.
Figure 8: Sensory experience increases truncation mediated by a given amount of feedforward inhibition via reduction of the NMDA receptor–mediated component.

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References

  1. Woolsey, T.A. & Van der Loos, H. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res. 17, 205–242 (1970).

    Article  CAS  PubMed  Google Scholar 

  2. Bureau, I., von Saint Paul, F. & Svoboda, K. Interdigitated paralemniscal and lemniscal pathways in the mouse barrel cortex. PLoS Biol. 4, e382 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Petreanu, L., Mao, T., Sternson, S.M. & Svoboda, K. The subcellular organization of neocortical excitatory connections. Nature 457, 1142–1145 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Porter, J.T., Johnson, C.K. & Agmon, A. Diverse types of interneurons generate thalamus-evoked feedforward inhibition in the mouse barrel cortex. J. Neurosci. 21, 2699–2710 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Swadlow, H.A. Thalamocortical control of feed-forward inhibition in awake somatosensory 'barrel' cortex. Phil. Trans. R. Soc. Lond. B 357, 1717–1727 (2002).

    Article  Google Scholar 

  6. Gabernet, L., Jadhav, S.P., Feldman, D.E., Carandini, M. & Scanziani, M. Somatosensory integration controlled by dynamic thalamocortical feed-forward inhibition. Neuron 48, 315–327 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Daw, M.I., Ashby, M.C. & Isaac, J.T. Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex. Nat. Neurosci. 10, 453–461 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Cruikshank, S.J., Lewis, T.J. & Connors, B.W. Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex. Nat. Neurosci. 10, 462–468 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Sun, Q.Q., Huguenard, J.R. & Prince, D.A. Barrel cortex microcircuits: thalamocortical feedforward inhibition in spiny stellate cells is mediated by a small number of fast-spiking interneurons. J. Neurosci. 26, 1219–1230 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bruno, R.M. & Sakmann, B. Cortex is driven by weak, but synchronously active, thalamocortical synapses. Science 312, 1622–1627 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Kremkow, J., Perrinet, L.U., Masson, G.S. & Aertsen, A. Functional consequences of correlated excitatory and inhibitory conductances in cortical networks. J. Comput. Neurosci. 28, 579–594 (2010).

    Article  PubMed  Google Scholar 

  12. Wang, H.P., Spencer, D., Fellous, J.M. & Sejnowski, T.J. Synchrony of thalamocortical inputs maximizes cortical reliability. Science 328, 106–109 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fox, K. Anatomical pathways and molecular mechanisms for plasticity in the barrel cortex. Neuroscience 111, 799–814 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Foeller, E. & Feldman, D.E. Synaptic basis for developmental plasticity in somatosensory cortex. Curr. Opin. Neurobiol. 14, 89–95 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Fox, K. A critical period for experience-dependent synaptic plasticity in rat barrel cortex. J. Neurosci. 12, 1826–1838 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shoykhet, M., Land, P.W. & Simons, D.J. Whisker trimming begun at birth or on postnatal day 12 affects excitatory and inhibitory receptive fields of layer IV barrel neurons. J. Neurophysiol. 94, 3987–3995 (2005).

    Article  PubMed  Google Scholar 

  17. Lee, S.H., Land, P.W. & Simons, D.J. Layer- and cell type–specific effects of neonatal whisker-trimming in adult rat barrel cortex. J. Neurophysiol. 97, 4380–4385 (2007).

    Article  PubMed  Google Scholar 

  18. Simons, D.J. & Land, P.W. Early experience of tactile stimulation influences organization of somatic sensory cortex. Nature 326, 694–697 (1987).

    Article  CAS  PubMed  Google Scholar 

  19. Stern, E.A., Maravall, M. & Svoboda, K. Rapid development and plasticity of layer 2/3 maps in rat barrel cortex in vivo. Neuron 31, 305–315 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Hull, C., Isaacson, J.S. & Scanziani, M. Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs. J. Neurosci. 29, 9127–9136 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Maffei, A., Nataraj, K., Nelson, S.B. & Turrigiano, G.G. Potentiation of cortical inhibition by visual deprivation. Nature 443, 81–84 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Sun, Q.Q. Experience-dependent intrinsic plasticity in interneurons of barrel cortex layer IV. J. Neurophysiol. 102, 2955–2973 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Allen, C.B., Celikel, T. & Feldman, D.E. Long-term depression induced by sensory deprivation during cortical map plasticity in vivo. Nat. Neurosci. 6, 291–299 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Hardingham, N., Wright, N., Dachtler, J. & Fox, K. Sensory deprivation unmasks a PKA-dependent synaptic plasticity mechanism that operates in parallel with CaMKII. Neuron 60, 861–874 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. Heynen, A.J. et al. Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation. Nat. Neurosci. 6, 854–862 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Yoon, B.J., Smith, G.B., Heynen, A.J., Neve, R.L. & Bear, M.F. Essential role for a long-term depression mechanism in ocular dominance plasticity. Proc. Natl. Acad. Sci. USA 106, 9860–9865 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kullmann, D.M. & Lamsa, K.P. Long-term synaptic plasticity in hippocampal interneurons. Nat. Rev. Neurosci. 8, 687–699 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Oren, I., Nissen, W., Kullmann, D.M., Somogyi, P. & Lamsa, K.P. Role of ionotropic glutamate receptors in long-term potentiation in rat hippocampal CA1 oriens–lacunosum moleculare interneurons. J. Neurosci. 29, 939–950 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mierau, S.B., Meredith, R.M., Upton, A.L. & Paulsen, O. Dissociation of experience-dependent and -independent changes in excitatory synaptic transmission during development of barrel cortex. Proc. Natl. Acad. Sci. USA 101, 15518–15523 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Philpot, B.D., Sekhar, A.K., Shouval, H.Z. & Bear, M.F. Visual experience and deprivation bidirectionally modify the composition and function of NMDA receptors in visual cortex. Neuron 29, 157–169 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Franks, K.M. & Isaacson, J.S. Synapse-specific downregulation of NMDA receptors by early experience: a critical period for plasticity of sensory input to olfactory cortex. Neuron 47, 101–114 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Binshtok, A.M., Fleidervish, I.A., Sprengel, R. & Gutnick, M.J. NMDA receptors in layer 4 spiny stellate cells of the mouse barrel cortex contain the NR2C subunit. J. Neurosci. 26, 708–715 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Espinosa, F. & Kavalali, E.T. NMDA receptor activation by spontaneous glutamatergic neurotransmission. J. Neurophysiol. 101, 2290–2296 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Das, S. et al. Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature 393, 377–381 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Al-Hallaq, R.A. et al. Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2 subunits. Mol. Pharmacol. 62, 1119–1127 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Wong, H.K. et al. Temporal and regional expression of NMDA receptor subunit NR3A in the mammalian brain. J. Comp. Neurol. 450, 303–317 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Monyer, H., Burnashev, N., Laurie, D.J., Sakmann, B. & Seeburg, P.H. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12, 529–540 (1994).

    Article  CAS  PubMed  Google Scholar 

  38. Morishita, W., Marie, H. & Malenka, R.C. Distinct triggering and expression mechanisms underlie LTD of AMPA and NMDA synaptic responses. Nat. Neurosci. 8, 1043–1050 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Bellone, C. & Nicoll, R.A. Rapid bidirectional switching of synaptic NMDA receptors. Neuron 55, 779–785 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Feldmeyer, D., Egger, V., Lubke, J. & Sakmann, B. Reliable synaptic connections between pairs of excitatory layer 4 neurones within a single 'barrel' of developing rat somatosensory cortex. J. Physiol. (Lond.) 521, 169–190 (1999).

    Article  CAS  Google Scholar 

  41. Petersen, C.C. & Sakmann, B. The excitatory neuronal network of rat layer 4 barrel cortex. J. Neurosci. 20, 7579–7586 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lefort, S., Tomm, C., Floyd Sarria, J.C. & Petersen, C.C. The excitatory neuronal network of the C2 barrel column in mouse primary somatosensory cortex. Neuron 61, 301–316 (2009).

    Article  CAS  PubMed  Google Scholar 

  43. Tamamaki, N. et al. Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J. Comp. Neurol. 467, 60–79 (2003).

    Article  CAS  PubMed  Google Scholar 

  44. Isaac, J.T., Crair, M.C., Nicoll, R.A. & Malenka, R.C. Silent synapses during development of thalamocortical inputs. Neuron 18, 269–280 (1997).

    Article  CAS  PubMed  Google Scholar 

  45. Agmon, A. & Connors, B.W. Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro. Neuroscience 41, 365–379 (1991).

    Article  CAS  PubMed  Google Scholar 

  46. Isaac, J.T., Oliet, S.H., Hjelmstad, G.O., Nicoll, R.A. & Malenka, R.C. Expression mechanisms of long-term potentiation in the hippocampus. J. Physiol. (Paris) 90, 299–303 (1996).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank C. McBain for discussions and Y. Yanagawa (Gunma University) for providing GAD67-GFP knockin mouse. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Program.

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  1. Developmental Synaptic Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

    Ramesh Chittajallu & John T R Isaac

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R.C. performed and analyzed the experiments. R.C. and J.T.R.I. designed the experiments and wrote the manuscript.

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Correspondence to Ramesh Chittajallu or John T R Isaac.

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Chittajallu, R., Isaac, J. Emergence of cortical inhibition by coordinated sensory-driven plasticity at distinct synaptic loci. Nat Neurosci 13, 1240–1248 (2010). https://doi.org/10.1038/nn.2639

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