Skip to main content
Log in

Contributions of GABAergic and glutamatergic mechanisms to isoflurane-induced suppression of thalamic somatosensory information transfer

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Indications for a pivotal role of the thalamocortical network in producing the state of anesthesia have come from in vivo animal studies as well as imaging studies in humans. We studied possible synaptic mechanisms of anesthesia-induced suppression of touch perception in the rat’s thalamus. Thalamocortical relay neurons (TCNs) receive ascending and descending glutamatergic excitatory inputs via NMDA and non-NMDA receptors (AMPAR) and are subjected to GABAAergic inhibitory input which shapes the sensory information conveyed to the cortex. The involvement of these synaptic receptors in the suppressive effects of the prototypic volatile anesthetic isoflurane was assessed by local iontophoretic administration of receptor agonists/antagonists during extracellular recordings of TCNs of the ventral posteromedial nucleus responding to whisker vibration in rats anesthetized with isoflurane concentrations of ∼0.9 vol.% (baseline) and ∼1.9 vol.% (ISO high). ISO high induced a profound suppression of response activity reflected by a conversion of the sustained vibratory responses to ON responses. Administration of NMDA, AMPA, or GABAAR antagonists caused a reversal to sustained responses in 88, 94 and 88% of the neurons, respectively, with a recovery to baseline levels of response activity. The data show that the block of thalamocortical transfer of tactile information under ISO high may result from an enhancement of GABAAergic inhibition and/or a reduction of glutamatergic excitation. Furthermore, they show that the ascending vibratory signals still reach the thalamic neurons under the high isoflurane concentration, indicating that this input is resistant to isoflurane while the attenuation of excitation may be brought about at the corticothalamic glutamatergic facilitatory input.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Alkire MT, Haier RJ, Fallon JH (2000) Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness. Conscious Cogn 9:370–386

    Article  PubMed  CAS  Google Scholar 

  • Alloway KD, Wallace MB, Johnson MJ (1994) Cross-correlation analysis of cuneothalamic interactions in the rat somatosensory system: influence of receptive field topography and comparisons with thalamocortical interactions. J Neurophysiol 72:1949–1972

    PubMed  CAS  Google Scholar 

  • Antognini JF, Buonocore MH, Disbrow EA, Carstens E (1997) Isoflurane anesthesia blunts cerebral responses to noxious and innocuous stimuli: a fMRI study. Life Sci 61:PL349–PL354

    Article  CAS  Google Scholar 

  • Carla V, Moroni F (1992) General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. Neurosci Lett 146:21–24

    Article  PubMed  CAS  Google Scholar 

  • Darian-Smith I, Rowe MJ, Sessle BJ (1968) “Tactile” stimulus intensity: information transmission by relay neurons in different trigeminal nuclei. Science 160:791–794

    Article  PubMed  CAS  Google Scholar 

  • Debarbieux F, Brunton J, Charpak S (1998) Effect of bicuculline on thalamic activity: a direct blockade of IAHP in reticularis neurons. J Neurophysiol 79:2911–2918

    PubMed  CAS  Google Scholar 

  • Deschênes M, Paradis M, Roy JP, Steriade M (1984) Electrophysiology of neurons of lateral thalamic nuclei in cat: resting properties and burst discharges. J Neurophysiol 51:1196–1219

    PubMed  Google Scholar 

  • De Sousa SL, Dickinson R, Lieb WR, Franks NP (2000) Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon. Anesthesiology 92:1055–1066

    Article  PubMed  Google Scholar 

  • Destexhe A (2000) Modelling corticothalamic feedback and the gating of the thalamus by the cerebral cortex. J Physiol (Paris) 94:391–410

    Article  CAS  Google Scholar 

  • Detsch O, Vahle-Hinz C, Kochs E, Siemers M, Bromm B (1999) Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer. Brain Res 829:77–89

    Article  PubMed  CAS  Google Scholar 

  • Detsch O, Vahle-Hinz C, Kochs E, Siemers M, Bromm B (2001) Differential susceptibility of successive stages of the somatosensory pathway to isoflurane anesthesia. Europ J Anaesthesiol 18 Suppl. 21:A-218

    Google Scholar 

  • Detsch O, Kochs E, Siemers M, Bromm B, Vahle-Hinz C (2002a) Differential effects of isoflurane on excitatory and inhibitory synaptic inputs to thalamic neurones in vivo. Br J Anaesth 89:294–300

    Article  CAS  Google Scholar 

  • Detsch O, Reeker W, Siemers M, Kochs E, Bromm B (2002b) Suppression of tactile information transfer by isoflurane within the central nervous system. In: Urban BW, Barann M (eds) Molecular and basic mechanisms of anesthesia. Pabst Sci Publ, Lengerich pp 484–492

    Google Scholar 

  • Ghosh S, Murray GM, Turman AB, Rowe MJ (1994) Corticothalamic influences on transmission of tactile information in the ventroposterolateral thalamus of the cat: effect of reversible inactivation of somatosensory cortical areas I and II. Exp Brain Res 100:276–286

    Article  PubMed  CAS  Google Scholar 

  • Golshani P, Liu X-B, Jones EG (2001) Differences in quantal amplitude reflect GluR4-subunit number at corticothalamic synapses on two populations of thalamic neurons. PNAS 98:4172–4177

    Article  PubMed  CAS  Google Scholar 

  • Gottschaldt K-M, Young DW (1977a) Properties of different functional types of neurons in the cat’s rostral trigeminal nuclei responding to sinus hair stimulation. J Physiol 272:57–84

    Google Scholar 

  • Gottschaldt K-M, Young DW (1977b) Quantitative aspects of responses in trigeminal relay neurones and interneurones following mechanical stimulation of sinus hairs and skin in the cat. J Physiol 272:85–103

    Google Scholar 

  • Hartings JA, Simons DJ (2000) Inhibition suppresses transmission of tonic vibrissa-evoked activity in the rat ventrobasal thalamus. J Neurosci 20 RC100:1–5

    Google Scholar 

  • Hentschke H, Schwarz C, Antkowiak B (2005) Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor-mediated inhibition. Eur J Neurosci 21:93–102

    Article  PubMed  Google Scholar 

  • Heyer EJ, Nowak LM, Macdonald RL (1981) Bicuculline: a convulsant with synaptic and nonsynaptic effects. Neurology 31:381–1390

    Google Scholar 

  • Hicks TP (1984) The history and development of microiontophoresis in experimental neurobiology. Prog Neurobiol 22:185–240

    Article  PubMed  CAS  Google Scholar 

  • Hicks TP, Metherate R, Landry P, Dykes RW (1986) Bicuculline-induced alterations of response properties in functionally identified ventroposterior thalamic neurones. Exp Brain Res 63:248–264

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann WE, Edelman G, Kochs E, Werner C, Segil L, Albrecht RF (1991) Cerebral autoregulation in awake versus isoflurane-anesthetized rats. Anesth Analg 73:753–757

    Google Scholar 

  • Hoogland PV, Wouterlood FG, Welker E, Van der Loos H (1991) Ultrastructure of giant and small thalamic terminals of cortical origin: a study of the projections from the barrel cortex in mice using Phaseolus vulgaris leuco-agglutinin (PHA-L). Exp Brain Res 87:159–172

    Article  PubMed  CAS  Google Scholar 

  • Ito M (1988) Response properties and topography of vibrissa-sensitive VPM neurons in the rat. J Neurophysiol 60:1181–1197

    PubMed  CAS  Google Scholar 

  • Jahnsen H, Llinás R (1984) Electrophysiological properties of guinea-pig thalamic neurones: an in vitro study. J Physiol 349:205–226

    PubMed  CAS  Google Scholar 

  • Khakh BS, Henderson G (2000) Modulation of fast synaptic transmission by presynaptic ligand-gated cation channels. J Autonom Nerv Sys 81:110–121

    Article  CAS  Google Scholar 

  • Krasowski MD, Harrison NL (1999) General anesthetic actions on ligand-gated ion channels. Cell Mol Life Sci 55:1278–1303

    Article  PubMed  CAS  Google Scholar 

  • Lee SM, Friedberg MH, Ebner FF (1994a) The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus: I. Assessment of receptive field changes following thalamic reticular nucleus lesions. J Neurophysiol 71:1702–1715

    CAS  Google Scholar 

  • Lee SM, Friedberg MH, Ebner FF (1994b) The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus: II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons. J Neurophysiol 71:1716–1726

    CAS  Google Scholar 

  • MacIver MB (1997) General anesthetic actions on transmission at glutamate and GABA synapses. In: Yaksh TL (ed) Anesthesia: biologic foundations. Lippincott-Raven, Philadelphia pp 277–286

    Google Scholar 

  • McCormick DA (1992) Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog Neurobiol 39:337–388

    Article  PubMed  CAS  Google Scholar 

  • Mineff EM, Weinberg RJ (2000) Differential synaptic distribution of AMPAR subunits in the ventral posterior and reticular thalamic nuclei of the rat. Neurosci 101:969–982

    Article  CAS  Google Scholar 

  • Minnery BS, Simons DJ (2003) Response properties of whisker-associated trigeminothalamic neurons in rat nucleus principalis. J Neurophysiol 89:40–56

    Article  PubMed  Google Scholar 

  • Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL (1997) Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors. Nature 389:385–389

    Article  PubMed  CAS  Google Scholar 

  • Pearce RA (2003) General anesthetic effects on GABAA receptors. In: Antognini JF, Carstens EE, Raines DE (eds) Neural mechanisms of anesthesia. Humana, Totowa pp 265–282

    Google Scholar 

  • Peoples RW, Weight FF (1997) Anesthetic actions on excitatory amino acid receptors. In: Yaksh TL (ed) Anesthesia: biologic foundations. Lippincott-Raven, Philadelphia, pp 239–258

    Google Scholar 

  • Perouansky M, Antognini JF (2003) Glutamate receptors: physiology and anesthetic pharmacology. In: Antognini JF, Carstens EE, Raines DE (eds) Neural mechanisms of anesthesia. Humana, Totowa pp 319–332

    Google Scholar 

  • Perouansky M, Hemmings HC, Pearce RA (2004) Anesthetic effects on glutamatergic neurotransmission: Lessons learned from a large synapse. Anesthesiology 100:470–472

    Article  PubMed  Google Scholar 

  • Salt TE, Eaton SA (1996) Functions of ionotropic and metabotropic glutamate receptors in sensory transmission in the mammalian thalamus. Prog Neurobiol 48:55–72

    Article  PubMed  CAS  Google Scholar 

  • Seutin V, Johnson SW (1999) Recent advances in the pharmacology of quaternary salts of bicuculline. Trends Pharmacol Sci 20:268–270

    Article  PubMed  CAS  Google Scholar 

  • Sherman SM, Guillery RW (1996) Functional organization of thalamocortical relays. J Neurophysiol 76:1367–1395

    PubMed  CAS  Google Scholar 

  • Steriade M, Jones EG, McCormick DA (1997) Thalamus. vol. I. Organisation and function. Elsevier, Amsterdam

  • Topf N, Jenkins A, Baron N, Harrison NL (2003) Effects of isoflurane on gamma-aminobutyric acid type A receptors activated by full and partial agonists. Anesthesiology 98:306–311

    Article  PubMed  CAS  Google Scholar 

  • Vahle-Hinz C, Gottschaldt KM (1983) Principal differences in the organization of the thalamic face representation in rodents and felids. In: Macchi G, Rustioni A, Spreafico R (eds) Somatosensory integration in the thalamus. Elsevier, Amsterdam pp 125–145

    Google Scholar 

  • Vahle-Hinz C, Hicks TP (2003) Temporal shaping of phasic neuronal responses by GABA-mediated and non-GABA-mediated mechanisms in the somatosensory thalamus of the rat. Exp Brain Res 153:310–321

    Article  PubMed  CAS  Google Scholar 

  • Vahle-Hinz C, Hicks TP, Gottschaldt KM (1994) Amino acids modify thalamo-cortical response transformation expressed by neurons of the ventrobasal complex. Brain Res 637:139–155

    Article  PubMed  CAS  Google Scholar 

  • Vahle-Hinz C, Detsch O, Siemers M, Kochs E, Bromm B (2001) Local GABAA receptor blockade reverses isoflurane’s suppressive effects on thalamic neurons in vivo. Anesth Analg 92:1578–1584

    Article  PubMed  CAS  Google Scholar 

  • Westphalen RI, Hemmings HC Jr (2003) Selective depression by general anesthetics of glutamate versus GABA release from isolated cortical nerve terminals. J Pharmacol Exp Ther 304:1188–1196

    Article  PubMed  CAS  Google Scholar 

  • White NS, Alkire MT (2003) Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness. NeuroImage 19:402–411

    Article  PubMed  Google Scholar 

  • Wu XS, Sun JY, Evers A, Crowder M, Wu LG (2004) Isoflurane inhibits transmitter release and the presynaptic action potential. Anesthesiology 100:663–670

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christiane Vahle-Hinz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vahle-Hinz, C., Detsch, O., Siemers, M. et al. Contributions of GABAergic and glutamatergic mechanisms to isoflurane-induced suppression of thalamic somatosensory information transfer. Exp Brain Res 176, 159–172 (2007). https://doi.org/10.1007/s00221-006-0604-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-006-0604-6

Keywords

Navigation