Experimental Brain Research

, 199:411 | Cite as

Theta burst and conventional low-frequency rTMS differentially affect GABAergic neurotransmission in the rat cortex

  • Jörn Trippe
  • Annika Mix
  • Selcen Aydin-Abidin
  • Klaus Funke
  • Alia Benali
Research Article

Abstract

Modified cortical excitability following repetitive transcranial magnetic stimulation (rTMS) may be related to short- or long-term synaptic plasticity of neuronal excitation but could also affect cortical inhibition. Therefore, in the rat we tested how three different rTMS protocols, intermittent and continuous theta-burst (iTBS, cTBS), and low-frequency 1 Hz stimulation, change the expression of GAD65, GAD67 and GAT-1 which are expressed in cortical inhibitory interneurons in an activity-dependent manner. Acutely (2 h), all protocols reduced the expression of GAD67 in frontal, motor, somatosensory and visual cortex but increased that of GAD65 and GAT-1 to different degree, with iTBS having the strongest acute effect. The initial decrease in GAD67 reversed after 1 day, leading to a strong increase in GAD67 expression for up to 7 days primarily in the frontal cortex in case of iTBS, cTBS and in all studied areas following 1 Hz rTMS. While also GAD65 and GAT-1 expression reversed after 1 day in case of iTBS and cTBS, 1 Hz rTMS induced a steady increase in GAD65 and GAT-1 expression during the 7 days investigated. Our data demonstrate that rTMS affects the expression of activity-dependent proteins of the cortical inhibitory interneurons. Besides common effects of low- (1 Hz) and high-frequency (TBS) stimulation on protein expression, differences in quantity and time course of changes point to differences in the contribution of possible neuronal subsystems. Further studies are needed to distinguish cell-type specific effects.

Keywords

Repetitive TMS Theta-burst stimulation GAD67 GAD65 GAT-1 Cortical inhibition Synaptic plasticity 

References

  1. Aydin-Abidin S, Trippe J, Funke K, Eysel UT, Benali A (2008) High- and low-frequency repetitive transcranial magnetic stimulation differentially activates c-Fos and zif268 protein expression in the rat brain. Exp Brain Res 188(2):249–261CrossRefPubMedGoogle Scholar
  2. Benali A, Leefken I, Eysel UT, Weiler E (2003) A computerized image analysis system for quantitative analysis of cells in histological brain sections. J Neurosci Meth 125(1–2):33–43CrossRefGoogle Scholar
  3. Benali A, Weiler E, Benali Y, Dinse HR, Eysel UT (2008) Excitation and inhibition jointly regulate cortical reorganization in adult rats. J Neurosci 28(47):12284–12293CrossRefPubMedGoogle Scholar
  4. Benson DL, Huntsman MM, Jones EG (1994) Activity-dependent changes in GAD and preprotachykinin mRNAs in visual cortex of adult monkeys. Cereb Cortex 4(1):40–51CrossRefPubMedGoogle Scholar
  5. Bergado-Acosta JR, Sangha S, Narayanan RT, Obata K, Pape HC, Stork O (2008) Critical role of the 65-kDa isoform of glutamic acid decarboxylase in consolidation and generalization of Pavlovian fear memory. Learn Mem 15(3):163–171CrossRefPubMedGoogle Scholar
  6. Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232(2):331–356PubMedGoogle Scholar
  7. Caputi A, Rozov A, Blatow M, Monyer H (2008) Two calretinin-positive GABAergic cell types in layer 2/3 of the mouse neocortex provide different forms of inhibition. Cerebr Cortex 19(6):1345–1359CrossRefGoogle Scholar
  8. Chaudhuri A, Nissanov J, Larocque S, Rioux L (1997) Dual activity maps in primate visual cortex produced by different temporal patterns of zif268 mRNA and protein expression. PNAS 94(6):2671–2675CrossRefPubMedGoogle Scholar
  9. Clement EA, Richard A, Thwaites M, Ailon J, Peters S, Dickson CT (2008) Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia. PLoS ONE 3(4):e2004CrossRefPubMedGoogle Scholar
  10. de Graaf R, Mason G, Patel A, Behar KL, Rothman DL (2003) In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism. NMR Biomed 16(6–7):339–357CrossRefPubMedGoogle Scholar
  11. Di Lazzaro V, Pilato F, Saturno E, Oliviero A, Dileone M, Mazzone P, Insola A, Tonali PA, Ranieri F, Huang YZ, Rothwell JC (2005) Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex. J Physiol 565(3):945–950CrossRefPubMedGoogle Scholar
  12. Di Lazzaro V, Pilato F, Dileone M, Profice P, Oliviero A, Mazzone P, Insola A, Ranieri F, Meglio M, Tonali PA, Rothwell JC (2008) The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. J Physiol 586(16):3871–3879CrossRefPubMedGoogle Scholar
  13. Esclapez M, Tillakaratne NJ, Kaufman DL, Tobin AJ, Houser CR (1994) Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms. J Neurosci 14(3):1834–1855PubMedGoogle Scholar
  14. Esser SK, Huber R, Massimini M, Peterson MJ, Ferrarelli F, Tononi G (2006) A direct demonstration of cortical LTP in humans: a combined TMS/EEG study. Brain Res Bull 69(1):86–94CrossRefPubMedGoogle Scholar
  15. Fagiolini M, Hensch TK (2000) Inhibitory threshold for critical-period activation in primary visual cortex. Nature 404(6774):183–186CrossRefPubMedGoogle Scholar
  16. Greif KF, Tillakaratne NJ, Erlander MG, Feldblum S, Tobin AJ (1992) Transient increase in expression of a glutamate decarboxylase (GAD) mRNA during the postnatal development of the rat striatum. Dev Biol 153(1):158–164CrossRefPubMedGoogle Scholar
  17. Griffiths R, Norman RI (1993) Effects of anaesthetics on uptake, synthesis and release of transmitters. Br J Anaesth 71(1):96–107CrossRefPubMedGoogle Scholar
  18. Hara K, Harris A (2002) The anesthetic mechanism of urethane: the effects on neurotransmitter-gated ion channels. Anest Pharmacol 94(2):313–318Google Scholar
  19. Hartmann M, Heumann R, Lessmann V (2001) Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses. EMBO J 20(21):5887–5897CrossRefPubMedGoogle Scholar
  20. Hentsch TK (2005) Critical period plasticity in local cortical circuits. Nat Rev Neurosci 6(11):877–888CrossRefGoogle Scholar
  21. Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45(2):201–206CrossRefPubMedGoogle Scholar
  22. Jiang B, Kitamura A, Yasuda H, Sohya K, Maruyama A, Yanagawa Y, Obata K, Tsumoto T (2004) Brain-derived neurotrophic factor acutely depresses excitatory synaptic transmission to GABAergic neurons in visual cortical slices. Eur J Neurosci 20(3):709–718CrossRefPubMedGoogle Scholar
  23. Jones MW, Errington ML, French PJ, Fine A, Bliss TV, Garel S, Charnay P, Bozon B, Laroche S, Davis S (2001) A requirement for the immediate early gene Zif268 in the expression of late LTP and long-term memories. Nat Neurosci 4(3):289–296CrossRefPubMedGoogle Scholar
  24. Kang TC, Kim HS, Seo MO, Choi SY, Kwon OS, Baek NI, Lee HY, Won MH (2001) The temporal alteration of GAD67/GAD65 ratio in the gerbil hippocampal complex following seizure. Brain Res 920(1–2):159–169CrossRefPubMedGoogle Scholar
  25. Kullmann DM, Lamsa KP (2007) Long-term synaptic plasticity in hippocampal interneurons. Nat Rev Neurosci 8(9):687–699CrossRefPubMedGoogle Scholar
  26. Lewis DA, Hashimoto T, Vok DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6(4):312–314CrossRefPubMedGoogle Scholar
  27. Liang F, Jones EG (1997a) Differential and time-dependent changes in gene expression for type II calcium/calmodulin-dependent protein kinase, 67 kDa glutamic acid decarboxylase, and glutamate receptor subunits in tetanus toxin-induced focal epilepsy. J Neurosci 17(6):2168–2180PubMedGoogle Scholar
  28. Liang F, Jones EG (1997b) Zif268 and Fos-like immunoreactivity in tetanus toxin-induced epilepsy: reciprocal changes in the epileptic focus and the surround. Brain Res 778(2):281–292CrossRefPubMedGoogle Scholar
  29. López-Bendito G, Sturgess K, Erdélyi F, Szabo G, Molnár Z, Paulsen O (2004) Preferential origin and layer destination of GAD65-GFP cortical interneurons. Cerebr Cortex 14:1122–1133CrossRefGoogle Scholar
  30. 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):793–807CrossRefPubMedGoogle Scholar
  31. Michaluk J, Antkiewicz-Michaluk L, Vetulani J (2001) Conditions of application of repeated transcranial magnetic stimulation to rats may mask the effects of the treatment. Pol J Pharmacol 53(6):685–687PubMedGoogle Scholar
  32. Minchin MC (1981) The effect of anaesthetics on the uptake and release of gamma-aminobutyrate and D-aspartate in rat brain slices. Brit J Pharmacol 73(3):681–689Google Scholar
  33. Patel AB, de Graaf RA, Martin DL, Battaglioli G, Behar KL (2006) Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo. J Neurochem 97(2):385–396CrossRefPubMedGoogle Scholar
  34. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, San DiegoGoogle Scholar
  35. Prince DA, Deisz RA, Thompson SM, Chagnac-Amitai Y (1992) Functional alterations in GABAergic inhibition during activity. Epilepsy Res (Suppl) 8:31–38Google Scholar
  36. Rees VH, Laurence DJ (1955) The correspondence with Beer’s law for the optical density of stained protein patterns on filter paper as a function of surface protein concentration. Clin Chem 1(5):329–344PubMedGoogle Scholar
  37. Rossini PM, Rossi S (2007) Transcranial magnetic stimulation: diagnostic, therapeutic, and research potential. Neurology 68(7):484–488CrossRefPubMedGoogle Scholar
  38. Siebner HR, Rothwell J (2003) Transcranial magnetic stimulation: new insights into representational cortical plasticity. Exp Brain Res 148(1):1–16CrossRefPubMedGoogle Scholar
  39. Sinclair MD (2003) A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. Can Vet J 44(11):885–897PubMedGoogle Scholar
  40. Stagg CJ, Wylezinska M, Matthews PM, Johansen-Berg H, Jezzard P, Rothwell JC, Bestmann S (2009) Neurochemical effects of theta burst stimulation as assessed by magnetic resonance spectroscopy. J Neurophysiol 101(6):2872–2877CrossRefPubMedGoogle Scholar
  41. Sun QQ, Zhang Z, Jiao Y, Zhang C, Szabó G, Erdélyi F (2009) Differential metabotropic glutamate receptor expression and modulation in two neocortical inhibitory networks. J Neurophysiol 101(5):2679–2692CrossRefPubMedGoogle Scholar
  42. Teo JT, Terranova C, Swayne O, Greenwood RJ, Rothwell JC (2009) Differing effects of intracortical circuits on plasticity. Exp Brain Res 193(4):555–563CrossRefPubMedGoogle Scholar
  43. Touge T, Gerschlager W, Brown P, Rothwell JC (2001) Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses. Clin Neurophysiol 112(11):2138–2145CrossRefPubMedGoogle Scholar
  44. Trippe J, Benali A, Weiler E, Mix A, Funke K (2008) Chronic reduction of parvalbumin expression in rat cortex following treatment with high-frequency intermittend theta-burst repetitive transcranial magnetic stimulation. FENS Abstr 6:122.18Google Scholar
  45. Tropea D, Kreiman G, Lyckman A, Mukherjee S, Yu H, Horng S, Sur M (2006) Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex. Nat Neurosci 9(5):660–668CrossRefPubMedGoogle Scholar
  46. Tsumoto T (1992) Long-term potentiation and long-term depression in the neocortex. Prog Neurobiol 39(2):209–228CrossRefPubMedGoogle Scholar
  47. Wang H, Wang X, Scheich H (1996) LTD and LTP induced by transcranial magnetic stimulation in auditory cortex. NeuroReport 7(2):521–525CrossRefPubMedGoogle Scholar
  48. Wei J, Wu JY (2008) Post-translational regulation of L-glutamic acid decarboxylase in the brain. Neurochem Res 33(8):1459–1465CrossRefPubMedGoogle Scholar
  49. Wei J, Davis KM, Wu H, Wu JY (2004) Protein phosphorylation of human brain glutamic acid decarboxylase (GAD)65 and GAD67 and its physiological implications. Biochemistry 43(20):6182–6189CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jörn Trippe
    • 1
  • Annika Mix
    • 1
  • Selcen Aydin-Abidin
    • 1
  • Klaus Funke
    • 1
  • Alia Benali
    • 1
  1. 1.Department of Neurophysiology, Medical FacultyRuhr-University BochumBochumGermany

Personalised recommendations