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Dynamics of neuronal assemblies are modulated by anaesthetics but not analgesics

Published online by Cambridge University Press:  01 July 2007

T. F. T. Collins
Affiliation:
Oxford University, Department of Pharmacology, Oxford, UK
E. O. Mann
Affiliation:
Oxford University, Department of Physiology, Oxford, UK
M. R. H. Hill
Affiliation:
Oxford University, Department of Pharmacology, Oxford, UK
E. J. Dommett
Affiliation:
Oxford University, Department of Pharmacology, Oxford, UK
S. A. Greenfield*
Affiliation:
Oxford University, Department of Pharmacology, Oxford, UK
*
Correspondence to: Susan A. Greenfield, Department of Pharmacology, Oxford University, Mansfield Road, Oxford, OX1 3QT, UK. E-mail: [email protected]; Tel: +441865 271852; Fax: +441865 271853
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Summary

Background and objective

Analgesics and anaesthetics have diverse synaptic actions that nonetheless have a common net inhibitory action on neuronal discharge. It is puzzling, therefore, that these two classes of compounds have fundamentally different affects, one blocking pain and the other consciousness. Indeed, beyond the isolated synapse, little is known of the larger scale mechanisms that mediate actual function, for example, transient neuronal assemblies. It was hypothesized that the two classes of drugs might have, respectively, differential effects on transient activation of these assemblies of neurons working together.

Methods

Hippocampal tissue from juvenile Wistar rats was used for in vitro optical imaging with voltage-sensitive dyes and simultaneous field potential recordings. The response to paired pulse stimulation of the hippocampus was recorded in the presence and absence of two types of analgesic (morphine and gabapentin) and two types of anaesthetic (thiopental and propofol).

Results

Optical imaging and electrophysiology used in parallel yield quite different results. Most consistently, the imaging technique was able to detect an enhanced period of activation following anaesthetic, but not analgesic application. This effect was not readily seen from electrophysiology field potential recordings.

Conclusions

These findings suggest that, irrespective of the effects of the two drug classes at a synaptic level, the dynamics of transient neuronal assemblies are modified selectively by anaesthetics and not analgesics.

Type
Original Article
Copyright
Copyright © European Society of Anaesthesiology 2007

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References

1.Mann, EO, Tominaga, T, Ichikawa, M, Greenfield, SA. Cholinergic modulation of the spatiotemporal pattern of hippocampal activity in vitro. Neuropharmacology 2005; 48: 118133.CrossRefGoogle ScholarPubMed
2.Grinvald, A, Lieke, EE, Frostig, RD, Hildesheim, R. Cortical point-spread function and long-range lateral interactions revealed by real-time optical imaging of Macaque monkey primary visual cortex. J Neurosci 1994; 14: 25452568.CrossRefGoogle ScholarPubMed
3.Greenfield, SA. The private life of the brain. London: Penguin, 2000.Google Scholar
4.Corigall, WA, Linseman, MA. A specific affect of morphine on evoked activity in the rat hippocampal slice. Brain Res 1980; 192: 227238.CrossRefGoogle Scholar
5.Swearengen, E, Chavkin, C. Comparison of opioid and GABA receptor control of excitability and membrane conductance in hippocampal CA1 pyramidal cells in rat. Neuropharmacology 1989; 28: 689697.CrossRefGoogle ScholarPubMed
6.Whittington, MA, Traub, RD, Faulkner, HJ, Jefferys, JGR, Chettiar, K. Morphine disrupts long-range synchrony of gamma oscillations in hippocampal slices. Proc Natl Acad Sci USA 1998; 95: 58075811.CrossRefGoogle ScholarPubMed
7.Bertrand, S, Nouel, D, Morin, F, Nagy, F, Lacaille, JC. Gabapentin actions on Kir3 currents and N-type Ca2+ channels via GABAB receptors in hippocampal pyramidal cells. Synapse 2003; 50: 95109.CrossRefGoogle ScholarPubMed
8.Bieda, MC, MacIver, MB. Major role for tonic GABAA conductances in anaesthetic suppression of intrinsic neuronal excitability. J Neurophysiol 2004; 92: 16581667.CrossRefGoogle ScholarPubMed
9.Peduto, VA, Concas, A, Santoro, G, Biggio, G, Gassa, GL. Biochemical and electrophysiological evidence that propofol enhances GABAergic transmission in the rat brain. Anesthesiology 1991; 75: 10001009.CrossRefGoogle ScholarPubMed
10.Orser, BA, Bertlik, M, Wang, LY, MacDonald, JF. Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-d-aspartate subtype of glutamate receptor in cultured rat hippocampal neurones. Br J Pharmacol 1995; 116: 17611768.CrossRefGoogle Scholar
11.Rehberg, B, Duch, DS. Suppression of central nervous system sodium channels by propofol. Anesthesiology 1999; 91: 512520.CrossRefGoogle ScholarPubMed
12.Inoue, Y, Shibuya, I, Kabashima, N et al. . The mechanism of inhibitory actions of propofol on rat supraoptic neurones. Anesthesiology 1999; 91: 167178.CrossRefGoogle Scholar
13.Funahashi, M, Higuchi, H, Miyawaki, T, Shimida, S, Matsuo, R. Propofol suppresses a hyperpolarization-activated inward current in rat hippocampal CA1 neurons. Neurosci Lett 2001; 311: 177180.CrossRefGoogle ScholarPubMed
14.Scwhieler, L, Delbro, DS, Engberg, G, Erhardt, S. The anaesthetic agent propofol interacts with GABAB-receptors: an electrophysiological study in rat. Life Sci 2003; 72: 27932801.Google Scholar
15.Hirota, K, Roth, SH, Fujimura, J, Masuda, A, Ito, Y. GABAergic mechanisms in the actions of general anaesthesics. Toxicol Lett 1998; 100–101: 203207.CrossRefGoogle Scholar
16.Faulkner, HJ, Traub, RD, Whittington, MA. Anaesthetic/amnesic agents disrupt beta frequency oscillations associated with potentiation of excitatory synaptic potentials in the rat hippocampal slice. Br J Pharmacol 1999; 128: 18131825.CrossRefGoogle ScholarPubMed
17.Faulkner, HJ, Traub, RD, Whittington, MA. Disruption of synchronous gamma oscillations in the rat hippocampal slice: a common mechanism of anaesthetic drug action. Br J Pharmacol 1998; 125: 483492.CrossRefGoogle ScholarPubMed
18.O’Mara, SM, Commins, S, Anderson, M. Synaptic plasticity in the hippocampal area CA1-subiculum projection: implications for theories of memory. Hippocampus 2000; 10: 447456.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
19.Dennett, DC. Consciousness explained. Boston: Brown, 1991.Google Scholar
20.Kinsbourne, M. The intralaminar thalamic nuclei: subjectivity pumps or attention-action coordinators? Conscious Cogn 1995; 4: 167171.CrossRefGoogle ScholarPubMed
21.Greenfield, SA. Mind, brain and consciousness. Br J Psychol 2002; 181: 9193.CrossRefGoogle ScholarPubMed
22.O’Brien, G, Opie, J. A connectionist theory of phenomenal experience. Behav Brain Sci 1999; 22: 127148.CrossRefGoogle ScholarPubMed
23.Pedroarena, C, Llinas, R. Dendritic calcium conductances generate high-frequency oscillation in thalamocortical neurons. Proc Natl Acad Sci USA 1997; 94: 724728.CrossRefGoogle ScholarPubMed
24.Llinas, R, Ribary, U, Contrreras, D, Pedroarena, C. The neuronal basis for consciousness. Phil Trans R Soc London B 1998; 353: 18411849.Google ScholarPubMed
25.Flohr, H. Sensations and brain processes. Behav Brain Res 1995; 71: 157161.CrossRefGoogle ScholarPubMed
26.Flohr, H, Glade, U, Motzko, D. The neural correlate of consciousness and the mechanisms of general anaesthesia. Toxicol Lett 1998; 100–101: 2329.CrossRefGoogle Scholar
27.Traub, RD, Whittington, MA, Colling, SB, Buzsaki, G, Jefferys, JGR. Analysis of gamma rhythms in the rat hippocampus in vitro and in vivo. J Physiol 1996; 493: 471484.CrossRefGoogle ScholarPubMed
28.Bragin, A, Jando, G, Nadasdy, Z, Hetke, J, Wise, G, Buzsaki, G. Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J Neurosci 1995; 15: 4760.CrossRefGoogle ScholarPubMed
29.Tiitinen, H, Sinkkonen, J, Reinikaien, K, Alho, K, Lavikainen, J, Naatanen, R. Selective attention enhances the auditory 40 Hz transient response in humans. Nature 1993; 364: 5960.CrossRefGoogle ScholarPubMed
30.De Pascalis, V, Ray, WJ. Effects on memory load on event-related patterns of 40 Hz EEG during cognitive and motor tasks. Int J Psychophysiol 1987; 28: 347352.Google Scholar