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Differing effects of intracortical circuits on plasticity

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Abstract

Practice of a motor task leads to an increase in amplitude of motor-evoked potentials (MEP) in the exercised muscle. This is termed practice-dependent plasticity, and is abolished by the NMDA antagonist dextromethorphan and the GABAA agonist lorazepam. Here, we sought to determine whether specific subtypes of GABAA circuits are responsible for this effect by comparing the action of the non-selective agonist, lorazepam with that of the selective GABAA-alpha1 receptor agonist, zolpidem. In seven healthy subjects, transcranial magnetic stimulation (TMS) was used to quantify changes in amplitude of MEP after practice of a ballistic motor task. In addition we measured how the same drugs affected MEP amplitudes and the excitability of a number of cortical inhibitory circuits [short-interval intracortical inhibition (SICI), short-interval afferent inhibition (SAI) and long-interval intracortical inhibition]. This allowed us to explore correlations between drugs effects in measures of cortical excitability and practice-dependent plasticity of MEP amplitudes. As previously reported, lorazepam increased SICI and decreased SAI, while zolpidem only decreased SAI. The new findings were that practice-dependent plasticity of MEPs was impaired by lorazepam but not zolpidem, and that this was negatively correlated with lorazepam-induced changes in SICI but not SAI. This suggests that the intracortical circuits involved in SICI (and not neurons expressing GABAA-alpha1 receptor subunits that are implicated in SAI) may be involved in controlling the amount of practice-dependent MEP plasticity.

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References

  • Ali AB, Thomson AM (2008) Synaptic alpha 5 subunit-containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex. Cereb Cortex 18(6):1260–1271

    Article  PubMed  Google Scholar 

  • Ascoli GA, Alonso-Nanclares L, Anderson SA, Barrionuevo G, Benavides-Piccione R, Burkhalter A, Buzsaki G, Cauli B, Defelipe J, Fairen A, Feldmeyer D, Fishell G, Fregnac Y, Freund TF, Gardner D, Gardner EP, Goldberg JH, Helmstaedter M, Hestrin S, Karube F, Kisvarday ZF, Lambolez B, Lewis DA, Marin O, Markram H, Munoz A, Packer A, Petersen CC, Rockland KS, Rossier J, Rudy B, Somogyi P, Staiger JF, Tamas G, Thomson AM, Toledo-Rodriguez M, Wang Y, West DC, Yuste R (2008) Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 9(7):557–568

    Article  PubMed  CAS  Google Scholar 

  • Bacci A, Rudolph U, Huguenard JR, Prince DA (2003) Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclasses. J Neurosci 23(29):9664–9674

    PubMed  CAS  Google Scholar 

  • Boroojerdi B, Ziemann U, Chen R, Butefisch CM, Cohen LG (2001) Mechanisms underlying human motor system plasticity. Muscle Nerve 24(5):602–613

    Article  PubMed  CAS  Google Scholar 

  • Butefisch CM, Davis BC, Wise SP, Sawaki L, Kopylev L, Classen J, Cohen LG (2000) Mechanisms of use-dependent plasticity in the human motor cortex. Proc Natl Acad Sci U S A 97(7):3661–3665

    Article  PubMed  CAS  Google Scholar 

  • Casasola C, Montiel T, Calixto E, Brailowsky S (2004) Hyperexcitability induced by GABA withdrawal facilitates hippocampal long-term potentiation. Neuroscience 126(1):163–171

    Article  PubMed  CAS  Google Scholar 

  • Classen J, Liepert J, Wise SP, Hallett M, Cohen LG (1998) “Rapid plasticity of human cortical movement representation induced by practice. J Neurophysiol 79(2):1117–1123

    PubMed  CAS  Google Scholar 

  • Di Lazzaro V, Oliviero A, Meglio M, Cioni B, Tamburrini G, Tonali P, Rothwell JC (2000) Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex. Clin Neurophysiol 111(5):794–799

    Article  PubMed  CAS  Google Scholar 

  • Di Lazzaro V, Pilato F, Dileone M, Profice P, Ranieri F, Ricci V, Bria P, Tonali PA, Ziemann U (2007) Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: a TMS study. Clin Neurophysiol 118(10):2207–2214

    Article  PubMed  CAS  Google Scholar 

  • Di Lazzaro V, Pilato F, Dileone M, Ranieri F, Ricci V, Profice P, Bria P, Tonali PA, Ziemann U (2006) GABAA receptor subtype specific enhancement of inhibition in human motor cortex. J Physiol 575(Pt 3):721–726

    Article  PubMed  CAS  Google Scholar 

  • Florian J, Muller-Dahlhaus M, Liu Y, Ziemann U (2008) Inhibitory circuits and the nature of their interactions in the human motor cortex a pharmacological TMS study. J Physiol 586(2):495–514

    Article  PubMed  CAS  Google Scholar 

  • Fritschy JM, Weinmann O, Wenzel A, Benke D (1998) Synapse-specific localization of NMDA and GABA(A) receptor subunits revealed by antigen-retrieval immunohistochemistry. J Comp Neurol 390(2):194–210

    Article  PubMed  CAS  Google Scholar 

  • Glazewski S, Herman C, McKenna M, Chapman PF, Fox K (1998) Long-term potentiation in vivo in layers II/III of rat barrel cortex. Neuropharmacology 37(4–5):581–592

    Article  PubMed  CAS  Google Scholar 

  • Hess G, Aizenman CD, Donoghue JP (1996) Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex. J Neurophysiol 75(5):1765–1778

    PubMed  CAS  Google Scholar 

  • Kawaguchi Y, Karube F, Kubota Y (2006) Dendritic branch typing and spine expression patterns in cortical nonpyramidal cells. Cereb Cortex 16(5):696–711

    Article  PubMed  Google Scholar 

  • Kawaguchi Y, Kubota Y (1997) GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cereb Cortex 7(6):476–486

    Article  PubMed  CAS  Google Scholar 

  • Kimiskidis VK, Papagiannopoulos S, Kazis DA, Sotirakoglou K, Vasiliadis G, Zara F, Kazis A, Mills KR (2006) Lorazepam-induced effects on silent period and corticomotor excitability. Exp Brain Res 173(4):603–611

    Article  PubMed  CAS  Google Scholar 

  • Klausberger T, Roberts JD, Somogyi P (2002) Cell type- and input-specific differences in the number and subtypes of synaptic GABA(A) receptors in the hippocampus. J Neurosci 22(7):2513–2521

    PubMed  CAS  Google Scholar 

  • Kubota Y, Kawaguchi Y (2000) Dependence of GABAergic synaptic areas on the interneuron type and target size. J Neurosci 20(1):375–386

    PubMed  CAS  Google Scholar 

  • Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519

    PubMed  CAS  Google Scholar 

  • Kyriakopoulos AA, Greenblatt DJ, Shader RI (1978) Clinical pharmacokinetics of lorazepam: a review. J Clin Psychiatry 39(10 Pt 2):16–23

    PubMed  CAS  Google Scholar 

  • Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Wu C (2004) Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 5(10):793–807

    Article  PubMed  CAS  Google Scholar 

  • McDonnell MN, Orekhov Y, Ziemann U (2006) The role of GABA(B) receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 173(1):86–93

    Article  PubMed  CAS  Google Scholar 

  • Miles R, Toth K, Gulyas AI, Hajos N, Freund TF (1996) Differences between somatic and dendritic inhibition in the hippocampus. Neuron 16(4):815–823

    Article  PubMed  CAS  Google Scholar 

  • Mohler H, Fritschy JM, Rudolph U (2002) A new benzodiazepine pharmacology. J Pharmacol Exp Ther 300(1):2–8

    Article  PubMed  CAS  Google Scholar 

  • Mohler H, Fritschy JM, Vogt K, Crestani F, Rudolph U (2005) Pathophysiology and pharmacology of GABA(A) receptors. Handb Exp Pharmacol 169:225–247

    Article  PubMed  Google Scholar 

  • Muellbacher W, Ziemann U, Boroojerdi B, Cohen L, Hallett M (2001) Role of the human motor cortex in rapid motor learning. Exp Brain Res 136(4):431–438

    Article  PubMed  CAS  Google Scholar 

  • Muellbacher W, Ziemann U, Wissel J, Dang N, Kofler M, Facchini S, Boroojerdi B, Poewe W, Hallett M (2002) Early consolidation in human primary motor cortex. Nature 415(6872):640–644

    Article  PubMed  CAS  Google Scholar 

  • Nusser Z, Sieghart W, Benke D, Fritschy JM, Somogyi P (1996) Differential synaptic localization of two major gamma-aminobutyric acid type A receptor alpha subunits on hippocampal pyramidal cells. Proc Natl Acad Sci U S A 93(21):11939–11944

    Article  PubMed  CAS  Google Scholar 

  • Pleger B, Schwenkreis P, Dinse HR, Ragert P, Hoffken O, Malin JP, Tegenthoff M (2003) Pharmacological suppression of plastic changes in human primary somatosensory cortex after motor learning. Exp Brain Res 148(4):525–532

    PubMed  Google Scholar 

  • Rioult-Pedotti MS, Friedman D, Donoghue JP (2000) Learning-induced LTP in neocortex. Science 290(5491):533–536

    Article  PubMed  CAS  Google Scholar 

  • Rioult-Pedotti MS, Friedman D, Hess G, Donoghue JP (1998) Strengthening of horizontal cortical connections following skill learning. Nat Neurosci 1(3):230–234

    Article  PubMed  CAS  Google Scholar 

  • Sailer A, Molnar GF, Cunic DI, Chen R (2002) Effects of peripheral sensory input on cortical inhibition in humans. J Physiol 544(Pt 2):617–629

    Article  PubMed  CAS  Google Scholar 

  • Salva P, Costa J (1995) Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet 29(3):142–153

    Article  PubMed  CAS  Google Scholar 

  • Sawaki L, Boroojerdi B, Kaelin-Lang A, Burstein AH, Butefisch CM, Kopylev L, Davis B, Cohen LG (2002) Cholinergic influences on use-dependent plasticity. J Neurophysiol 87(1):166–171

    PubMed  CAS  Google Scholar 

  • Segev I, Burke R (eds) (1998) Methods in neuronal modeling. MIT Press, Cambridge

    Google Scholar 

  • Steele PM, Mauk MD (1999) Inhibitory control of LTP and LTD: stability of synapse strength. J Neurophysiol 81(4):1559–1566

    PubMed  CAS  Google Scholar 

  • Stefan K, Wycislo M, Classen J (2004) Modulation of associative human motor cortical plasticity by attention. J Neurophysiol 92(1):66–72

    Article  PubMed  Google Scholar 

  • Tokimura H, Di Lazzaro V, Tokimura Y, Oliviero A, Profice P, Insola A, Mazzone P, Tonali P, Rothwell JC (2000) Short latency inhibition of human hand motor cortex by somatosensory input from the hand. J Physiol 523(Pt 2):503–513

    Article  PubMed  CAS  Google Scholar 

  • Wassermann EM, Samii A, Mercuri B, Ikoma K, Oddo D, Grill SE, Hallett M (1996) Responses to paired transcranial magnetic stimuli in resting, active, and recently activated muscles. Exp Brain Res 109(1):158–163

    Article  PubMed  CAS  Google Scholar 

  • Xiang Z, Huguenard JR, Prince DA (1998) Cholinergic switching within neocortical inhibitory networks. Science 281(5379):985–988

    Article  PubMed  CAS  Google Scholar 

  • Xiang Z, Huguenard JR, Prince DA (2002) Synaptic inhibition of pyramidal cells evoked by different interneuronal subtypes in layer v of rat visual cortex. J Neurophysiol 88(2):740–750

    PubMed  Google Scholar 

  • Ziemann U (2004) TMS and drugs. Clin Neurophysiol 115(8):1717–1729

    Article  PubMed  CAS  Google Scholar 

  • Ziemann U, Corwell B, Cohen LG (1998a) Modulation of plasticity in human motor cortex after forearm ischemic nerve block. J Neurosci 18(3):1115–1123

    PubMed  CAS  Google Scholar 

  • Ziemann U, Hallett M, Cohen LG (1998b) Mechanisms of deafferentation-induced plasticity in human motor cortex. J Neurosci 18(17):7000–7007

    PubMed  CAS  Google Scholar 

  • Ziemann U, Muellbacher W, Hallett M, Cohen LG (2001) Modulation of practice-dependent plasticity in human motor cortex. Brain 124(Pt 6):1171–1181

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Ms Rima Gupta, Clinical Trials Pharmacist at the National Hospital for Neurology and Neurosurgery, London, for preparation and dispensing the drug. This study received support from the Medical Research Council and the Wellington Fund.

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Authors and Affiliations

  1. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London, WC1N 3BG, UK

    J. T. H. Teo, C. Terranova, O. Swayne, R. J. Greenwood & J. C. Rothwell

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  1. J. T. H. Teo
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  2. C. Terranova
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  3. O. Swayne
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  4. R. J. Greenwood
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  5. J. C. Rothwell
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Correspondence to J. T. H. Teo.

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Teo, J.T.H., Terranova, C., Swayne, O. et al. Differing effects of intracortical circuits on plasticity. Exp Brain Res 193, 555–563 (2009). https://doi.org/10.1007/s00221-008-1658-4

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  • DOI: https://doi.org/10.1007/s00221-008-1658-4

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