Postnatal Maturation and Experience-Dependent Plasticity of Inhibitory Circuits in Barrel Cortex



Sensory experience drives the refinement of sensory maps in developing adult sensory cortices (Wiesel and Hubel 1974; Stryker 1978; Crair et al. 1998; Feldman and Brecht 2005). Tremendous progress has been made toward understanding the process of maturation of excitatory networks. Cortical inhibition has also been shown to play a vital role in the regulation of critical periods for sensory plasticity (Hensch 2005). However, it is unclear whether neocortical inhibitory networks exhibit experience-dependent postnatal maturation. In my laboratory, we employ the so-called “barrel cortex” (Woolsey and Van der 1970) that, represents the individual whiskers on the snout of rodents. The map exhibits plasticity throughout life, in that under- or over-stimulation of a whisker is reflected by contraction or expansion, respectively, of the barrel representing it in the primary somatosensory cortex (Simons and Land 1987). This review focuses on the mechanisms underlying activity-dependent regulation of neocortical inhibitory circuits and the roles of inhibition in somatosensory cortical map plasticity during postnatal development. The focus will be placed on the following questions related to experience-dependent plasticity of neocortical inhibitory networks. (1) How do intrinsic and synaptic properties of inhibitory circuits in barrel cortex change during postnatal maturation? (2) How does sensory stimulation or deprivation affect the maturation of inhibitory circuits? (3) Does the maturation of neocortical inhibitory circuits proceed in an activity-dependent manner or do they develop independently of sensory inputs? (4) What are the molecular and cellular mechanisms that underlie the activity-dependent or -independent maturation of inhibitory networks?


GABAA Receptor Sensory Experience Excitatory Neuron Intracortical Inhibition Sensory Deprivation 



I thank Chunzhao Zhang, Yuanyuan Jiao, Leah Selby and Andrew Young for their help and excellent assistance in all studies described in this chapter. I thank Dr. Yuchio Yanagawa at the Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine for the generous gift of GAD67-GFP mouse. My work is supported by NIH. Most of work dealing with the properties of excitatory neurons and excitatory synapses in the barrel cortex could not be cited here due to the focus of this book on the GABAergic system. I apologize to my colleagues for such necessary omissions.


  1. Agmon A, Hollrigel G, O’Dowd DK (1996) Functional GABAergic synaptic connection in neonatal mouse barrel cortex. J Neurosci 16:4684–4695PubMedGoogle Scholar
  2. Ali AB, Bannister AP, Thomson AM (2007) Robust correlations between action potential duration and the properties of synaptic connections in layer 4 interneurones in neocortical slices from juvenile rats and adult rat and cat. J Physiol 580:149–169CrossRefPubMedGoogle Scholar
  3. Barth AL, Gerkin RC, Dean KL (2004) Alteration of neuronal firing properties after in vivo experience in a FosGFP transgenic mouse. J Neurosci 24:6466–6475CrossRefPubMedGoogle Scholar
  4. Baude A, Nusser Z, Roberts JD, Mulvihill E, McIlhinney RA, Somogyi P (1993) The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11:771–787CrossRefPubMedGoogle Scholar
  5. Bruno RM, Simons DJ (2002) Feedforward mechanisms of excitatory and inhibitory cortical receptive fields. J Neurosci 22:10966–10975PubMedGoogle Scholar
  6. Castro-Alamancos MA (2000) Origin of synchronized oscillations induced by neocortical disinhibition in vivo. J Neurosci 20:9195–9206PubMedGoogle Scholar
  7. Connors BW, Gutnick MJ, Prince DA (1982) Electrophysiological properties of neocortical neurons in vitro. J Neurophysiol 48:1302–1320PubMedGoogle Scholar
  8. Crair MC, Gillespie DC, Stryker MP (1998) The role of visual experience in the development of columns in cat visual cortex. Science 279:566–570CrossRefPubMedGoogle Scholar
  9. Cruikshank SJ, Lewis TJ, Connors BW (2007) Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex. Nat Neurosci 10:462–468PubMedGoogle Scholar
  10. Dalezios Y, Lujan R, Shigemoto R, Roberts JD, Somogyi P (2002) Enrichment of mGluR7a in the presynaptic active zones of GABAergic and non-GABAergic terminals on interneurons in the rat somatosensory cortex. Cereb Cortex 12:961–974CrossRefPubMedGoogle Scholar
  11. Daw MI, Ashby MC, Isaac JT (2007) Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex. Nat Neurosci 10:453–461CrossRefPubMedGoogle Scholar
  12. Feldman DE, Brecht M (2005) Map plasticity in somatosensory cortex. Science 310:810–815CrossRefPubMedGoogle Scholar
  13. Feldman DE, Nicoll RA, Malenka RC (1999) Synaptic plasticity at thalamocortical synapses in developing rat somatosensory cortex: LTP, LTD, and silent synapses. J Neurobiol 41:92–101CrossRefPubMedGoogle Scholar
  14. Feldman DE, Nicoll RA, Malenka RC, Isaac JT (1998) Long-term depression at thalamocortical synapses in developing rat somatosensory cortex. Neuron 21:347–357CrossRefPubMedGoogle Scholar
  15. Filipkowski RK, Rydz M, Berdel B, Morys J, Kaczmarek L (2000) Tactile experience induces c-fos expression in rat barrel cortex. Learn Mem 7:116–122CrossRefPubMedGoogle Scholar
  16. Filipkowski RK, Rydz M, Kaczmarek L (2001) Expression of c-Fos, Fos B, Jun B, and Zif268 transcription factor proteins in rat barrel cortex following apomorphine-evoked whisking behavior. Neuroscience 106:679–688CrossRefPubMedGoogle Scholar
  17. Fiszman ML, Barberis A, Lu C, Fu Z, Erdelyi F, Szabo G, Vicini S (2005) NMDA receptors increase the size of GABAergic terminals and enhance GABA release. J Neurosci 25:2024–2031CrossRefPubMedGoogle Scholar
  18. Fuchs JL, Salazar E (1998) Effects of whisker trimming on GABA(A) receptor binding in the barrel cortex of developing and adult rats. J Comp Neurol 395:209–216CrossRefPubMedGoogle Scholar
  19. Fukuda T, Kosaka T, Singer W, Galuske RA (2006) Gap junctions among dendrites of cortical GABAergic neurons establish a dense and widespread intercolumnar network. J Neurosci 26:3434–3443CrossRefPubMedGoogle Scholar
  20. Galarreta M, Hestrin S (2002) Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex. Proc Natl Acad Sci U S A 99:12438–12443CrossRefPubMedGoogle Scholar
  21. Gianfranceschi L, Siciliano R, Walls J, Morales B, Kirkwood A, Huang ZJ, Tonegawa S, Maffei L (2003) Visual cortex is rescued from the effects of dark rearing by overexpression of BDNF. Proc Natl Acad Sci U S A 100:12486–12491CrossRefPubMedGoogle Scholar
  22. Gibson JR, Beierlein M, Connors BW (2005) Functional properties of electrical synapses between inhibitory interneurons of neocortical layer 4. J Neurophysiol 93:467–480CrossRefPubMedGoogle Scholar
  23. Glorioso C, Sabatini M, Unger T, Hashimoto T, Monteggia LM, Lewis DA, Mirnics K (2006) Specificity and timing of neocortical transcriptome changes in response to BDNF gene ablation during embryogenesis or adulthood. Mol Psychiatry 11:633–648CrossRefPubMedGoogle Scholar
  24. Golshani P, Truong H, Jones EG (1997) Developmental expression of GABA(A) receptor subunit and GAD genes in mouse somatosensory barrel cortex. J Comp Neurol 383:199–219CrossRefPubMedGoogle Scholar
  25. Heinen K, Bosman LW, Spijker S, van Pelt J, Smit AB, Voorn P, Baker RE, Brussaard AB (2004) GABAA receptor maturation in relation to eye opening in the rat visual cortex. Neuroscience 124:161–171CrossRefPubMedGoogle Scholar
  26. Hensch TK (2005) Critical period plasticity in local cortical circuits. Nat Rev Neurosci 6:877–888CrossRefPubMedGoogle Scholar
  27. Hensch TK, Stryker MP (2004) Columnar architecture sculpted by GABA circuits in developing cat visual cortex. Science 303:1678–1681CrossRefPubMedGoogle Scholar
  28. Itami C, Kimura F, Nakamura S (2007) Brain-derived neurotrophic factor regulates the maturation of layer 4 fast-spiking cells after the second postnatal week in the developing barrel cortex. J Neurosci 27:2241–2252CrossRefPubMedGoogle Scholar
  29. Iwasato T, Datwani A, Wolf AM, Nishiyama H, Taguchi Y, Tonegawa S, Knopfel T, Erzurumlu RS, Itohara S (2000) Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex. Nature 406:726–731CrossRefPubMedGoogle Scholar
  30. Iwasato T, Erzurumlu RS, Huerta PT, Chen DF, Sasaoka T, Ulupinar E, Tonegawa S (1997) NMDA receptor-dependent refinement of somatotopic maps. Neuron 19:1201–1210CrossRefPubMedGoogle Scholar
  31. Jiao Y, Zhang C, Yanagawa Y, Sun QQ (2006) Major effects of sensory experiences on the neocortical inhibitory circuits. J Neurosci 26:8691–8701CrossRefPubMedGoogle Scholar
  32. Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC (1995) Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci 18:527–535CrossRefPubMedGoogle Scholar
  33. Kelly MK, Carvell GE, Kodger JM, Simons DJ (1999) Sensory loss by selected whisker removal produces immediate disinhibition in the somatosensory cortex of behaving rats. J Neurosci 19:9117–9125PubMedGoogle Scholar
  34. Kiser PJ, Cooper NG, Mower GD (1998) Expression of two forms of glutamic acid decarboxylase (GAD67 and GAD65) during postnatal development of rat somatosensory barrel cortex. J Comp Neurol 402:62–74CrossRefPubMedGoogle Scholar
  35. Knott GW, Holtmaat A, Wilbrecht L, Welker E, Svoboda K (2006) Spine growth precedes synapse formation in the adult neocortex in vivo. Nat Neurosci 9:1117–1124CrossRefPubMedGoogle Scholar
  36. Knott GW, Quairiaux C, Genoud C, Welker E (2002) Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice. Neuron 34:265–273CrossRefPubMedGoogle Scholar
  37. Kriegstein AR, Suppes T, Prince DA (1987) Cellular and synaptic physiology and epileptogenesis of developing rat neocortical neurons in vitro. Brain Res 431:161–171PubMedGoogle Scholar
  38. Land PW, de Blas AL, Reddy N (1995) Immunocytochemical localization of GABAA receptors in rat somatosensory cortex and effects of tactile deprivation. Somatosens Mot Res 12:127–141CrossRefPubMedGoogle Scholar
  39. Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A, Noebels JL, Paylor R, Morgan JI, Leonard CS, Rudy B (2000) Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J Neurosci 20:9071–9085PubMedGoogle Scholar
  40. Lee SH, Land PW, Simons DJ (2007) Layer- and cell-type-specific effects of neonatal whisker-trimming in adult rat barrel cortex. J Neurophysiol 97:4380–4385CrossRefPubMedGoogle Scholar
  41. Lien CC, Mu Y, Vargas-Caballero M, Poo MM (2006) Visual stimuli-induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors. Nat Neurosci 9:372–380CrossRefPubMedGoogle Scholar
  42. Liu XB, Jones EG (2003) Fine structural localization of connexin-36 immunoreactivity in mouse cerebral cortex and thalamus. J Comp Neurol 466:457–467CrossRefPubMedGoogle Scholar
  43. Liu XB, Munoz A, Jones EG (1998) Changes in subcellular localization of metabotropic glutamate receptor subtypes during postnatal development of mouse thalamus. J Comp Neurol 395:450–465CrossRefPubMedGoogle Scholar
  44. Long MA, Cruikshank SJ, Jutras MJ, Connors BW (2005) Abrupt maturation of a spike-synchronizing mechanism in neocortex. J Neurosci 25:7309–7316CrossRefPubMedGoogle Scholar
  45. Lu B, Pang PT, Woo NH (2005) The yin and yang of neurotrophin action. Nat Rev Neurosci 6:603–614CrossRefPubMedGoogle Scholar
  46. Lu HC, Gonzalez E, Crair MC (2001) Barrel cortex critical period plasticity is independent of changes in NMDA receptor subunit composition. Neuron 32:619–634CrossRefPubMedGoogle Scholar
  47. Luhmann HJ, Prince DA (1991) Postnatal maturation of the GABAergic system in rat neocortex. J Neurophysiol 65:247–263PubMedGoogle Scholar
  48. Lujan R, Roberts JD, Shigemoto R, Ohishi H, Somogyi P (1997) Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1 alpha, mGluR2 and mGluR5, relative to neurotransmitter release sites. J Chem Neuroanat 13:219–241CrossRefPubMedGoogle Scholar
  49. Ma Y, Hu H, Berrebi AS, Mathers PH, Agmon A (2006) Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice. J Neurosci 26:5069–5082CrossRefPubMedGoogle Scholar
  50. Maier DL, McCasland JS (1997) Calcium-binding protein phenotype defines metabolically distinct groups of neurons in barrel cortex of behaving hamsters. Exp Neurol 145:71–80CrossRefPubMedGoogle Scholar
  51. Mancilla JG, Lewis TJ, Pinto DJ, Rinzel J, Connors BW (2007) Synchronization of electrically coupled pairs of inhibitory interneurons in neocortex. J Neurosci 27:2058–2073CrossRefPubMedGoogle Scholar
  52. Massengill JL, Smith MA, Son DI, O’Dowd DK (1997) Differential expression of K4-AP currents and Kv3.1 potassium channel transcripts in cortical neurons that develop distinct firing phenotypes. J Neurosci 17:3136–3147PubMedGoogle Scholar
  53. McCasland JS, Hibbard LS (1997) GABAergic neurons in barrel cortex show strong, whisker-dependent metabolic activation during normal behavior. J Neurosci 17:5509–5527PubMedGoogle Scholar
  54. McCasland JS, Hibbard LS, Rhoades RW, Woolsey TA (1997) Activation of a wide-spread network of inhibitory neurons in barrel cortex. Somatosens Mot Res 14:138–147CrossRefPubMedGoogle Scholar
  55. McCormick DA, Connors BW, Lighthall JW, Prince DA (1985) Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J Neurophysiol 54:782–806PubMedGoogle Scholar
  56. McCormick DA, Prince DA (1987) Post-natal development of electrophysiological properties of rat cerebral cortical pyramidal neurones. J Physiol 393:743–762PubMedGoogle Scholar
  57. Micheva KD, Beaulieu C (1995) Neonatal sensory deprivation induces selective changes in the quantitative distribution of GABA-immunoreactive neurons in the rat barrel field cortex. J Comp Neurol 361:574–584CrossRefPubMedGoogle Scholar
  58. Micheva KD, Beaulieu C (1997) Development and plasticity of the inhibitory neocortical circuitry with an emphasis on the rodent barrel field cortex: a review. Can J Physiol Pharmacol 75:470–478CrossRefPubMedGoogle Scholar
  59. Montoro RJ, Yuste R (2004) Gap junctions in developing neocortex: a review. Brain Res Brain Res Rev 47:216–226CrossRefPubMedGoogle Scholar
  60. Moore CI, Nelson SB (1998) Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J Neurophysiol 80:2882–2892PubMedGoogle Scholar
  61. Nadarajah B, Parnavelas JG (1999) Gap junction-mediated communication in the developing and adult cerebral cortex. Novartis Found Symp 219:157–170PubMedGoogle Scholar
  62. Nadarajah B, Thomaidou D, Evans WH, Parnavelas JG (1996) Gap junctions in the adult cerebral cortex: regional differences in their distribution and cellular expression of connexins. J Comp Neurol 376:326–342CrossRefPubMedGoogle Scholar
  63. Owens DF, Liu XL, Kriegstein AR (1999) Changing properties of GABAA receptor-mediated signaling during early neocortical development. J Neurophysiol 82:570–583PubMedGoogle Scholar
  64. Pallas SL, Wenner P, Gonzalez-Islas C, Fagiolini M, Razak KA, Kim G, Sanes D, Roerig B (2006) Developmental plasticity of inhibitory circuitry. J Neurosci 26:10358–10361CrossRefPubMedGoogle Scholar
  65. Porter JT, Johnson CK, Agmon A (2001) Diverse types of interneurons generate thalamus-evoked feedforward inhibition in the mouse barrel cortex. J Neurosci 21:2699–2710PubMedGoogle Scholar
  66. Prince DA (1999) Epileptogenic neurons and circuits. Adv Neurol 79:665–684PubMedGoogle Scholar
  67. Quairiaux C, Armstrong-James M, Welker E (2007) Modified sensory processing in the barrel cortex of the adult mouse after chronic whisker stimulation. J Neurophysiol 97:2130–2147CrossRefPubMedGoogle Scholar
  68. Razak KA, Pallas SL (2006) Dark rearing reveals the mechanism underlying stimulus size tuning of superior colliculus neurons. Vis Neurosci 23:741–748CrossRefPubMedGoogle Scholar
  69. Rema V, Ebner FF (1996) Postnatal changes in NMDAR1 subunit expression in the rat trigeminal pathway to barrel field cortex. J Comp Neurol 368:165–184CrossRefPubMedGoogle Scholar
  70. Rice FL, Van der LH (1977) Development of the barrels and barrel field in the somatosensory cortex of the mouse. J Comp Neurol 171:545–560CrossRefPubMedGoogle Scholar
  71. Rivera C, Voipio J, Payne JA, Ruusuvuori E, Lahtinen H, Lamsa K, Pirvola U, Saarma M, Kaila K (1999) The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397:251–255CrossRefPubMedGoogle Scholar
  72. Shoykhet M, Land PW, Simons DJ (2005) Whisker trimming begun at birth or on postnatal day 12 affects excitatory and inhibitory receptive fields of layer IV barrel neurons. J Neurophysiol 94:3987–3995CrossRefPubMedGoogle Scholar
  73. Silberberg G, Bethge M, Markram H, Pawelzik K, Tsodyks M (2004) Dynamics of population rate codes in ensembles of neocortical neurons. J Neurophysiol 91:704–709CrossRefPubMedGoogle Scholar
  74. Simons DJ, Land PW (1987) Early experience of tactile stimulation influences organization of somatic sensory cortex. Nature 326:694–697CrossRefPubMedGoogle Scholar
  75. Spires TL, Molnar Z, Kind PC, Cordery PM, Upton AL, Blakemore C, Hannan AJ (2005) Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signalling. Cereb Cortex 15:385–393CrossRefPubMedGoogle Scholar
  76. Staiger JF, Masanneck C, Bisler S, Schleicher A, Zuschratter W, Zilles K (2002) Excitatory and inhibitory neurons express c-Fos in barrel-related columns after exploration of a novel environment. Neuroscience 109:687–699CrossRefPubMedGoogle Scholar
  77. Stryker MP (1978) Postnatal development of ocular dominance columns in layer IV of the cat’s visual cortex and the effects of monocular deprivation. Arch Ital Biol 116:420–426PubMedGoogle Scholar
  78. Sun QQ, Huguenard JR, Prince DA (2006) Barrel cortex microcircuits: thalamocortical feedforward inhibition in spiny stellate cells is mediated by a small number of fast-spiking interneurons. J Neurosci 26:1219–1230CrossRefPubMedGoogle Scholar
  79. Sun QQ, Zhang Z, Jiao Y, Zhang C, Szabo G, Erdelyi F (2009) Differential metabotropic glutamate receptor expression and modulation in two neocortical inhibitory networks. J Neurophysiol 101:2679–2692CrossRefPubMedGoogle Scholar
  80. Swadlow HA (2002) Thalamocortical control of feed-forward inhibition in awake somatosensory ‘barrel’ cortex. Philos Trans R Soc Lond B Biol Sci 357:1717–1727CrossRefPubMedGoogle Scholar
  81. Swadlow HA (2003) Fast-spike interneurons and feedforward inhibition in awake sensory neocortex. Cereb Cortex 13:25–32CrossRefPubMedGoogle Scholar
  82. Varju P, Katarova Z, Madarasz E, Szabo G (2001) GABA signalling during development: new data and old questions. Cell Tissue Res 305:239–246CrossRefPubMedGoogle Scholar
  83. Wang Y, Gupta A, Toledo-Rodriguez M, Wu CZ, Markram H (2002) Anatomical, physiological, molecular and circuit properties of nest basket cells in the developing somatosensory cortex. Cereb Cortex 12:395–410CrossRefPubMedGoogle Scholar
  84. Wang Y, Toledo-Rodriguez M, Gupta A, Wu C, Silberberg G, Luo J, Markram H (2004) Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat. J Physiol 561:65–90CrossRefPubMedGoogle Scholar
  85. West AE, Griffith EC, Greenberg ME (2002) Regulation of transcription factors by neuronal activity. Nat Rev Neurosci 3:921–931CrossRefPubMedGoogle Scholar
  86. Wiesel TN, Hubel DH (1974) Ordered arrangement of orientation columns in monkeys lacking visual experience. J Comp Neurol 158:307–318CrossRefPubMedGoogle Scholar
  87. Wilent WB, Contreras D (2005) Dynamics of excitation and inhibition underlying stimulus selectivity in rat somatosensory cortex. Nat Neurosci 8:1364–1370CrossRefPubMedGoogle Scholar
  88. Woo NH, Lu B (2006) Regulation of cortical interneurons by neurotrophins: from development to cognitive disorders. Neuroscientist 12:43–56CrossRefPubMedGoogle Scholar
  89. Woolsey TA, Van der LH (1970) 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 17:205–242CrossRefPubMedGoogle Scholar
  90. Xiang Z, Huguenard JR, Prince DA (1998) Cholinergic switching within neocortical inhibitory networks. Science 281:985–988CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Zoology and Physiology, Graduate Neuroscience ProgramUniversity of WyomingLaramieUSA

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