Effect of halothane on type 2 immobility‐related hippocampal theta field activity and theta‐on/theta‐off cell discharges

Rats were studied in acute and chronic (freely moving) recording conditions during exposure to different levels of the volatile anesthetic halothane, in order to assess effects on hippocampal theta field activity in the chronic condition and on theta‐related cellular discharges in the acute condition. Previous work has shown that the generation of hippocampal type 2 theta depends on the coactivation of cholinergic and GABAergic inputs from the medial septum. Based on these data and recent findings that halothane acts on interneuron GABAA receptors, we predicted that exposure of rats to subanesthetic levels would result in the induction of type 2 theta field activity. In the chronic condition, exposure to subanesthetic levels of halothane (0.5–1.0 vol %) was found to induce theta field activity during periods of immobility (type 2 theta) with a mean increase of 39% in amplitude (mV) compared to control levels during movement. The total percentage of signal power (V2) associated with peak theta frequencies (80% compared to control levels of 47%) was also increased by halothane. Over the whole range of administered halothane concentrations, theta field frequency progressively declined from a mean peak frequency of 6.5 ± 0.8 Hz at 0.5 vol % halothane to a mean peak frequency of 4.0 ± 1.8 Hz at 2.0 vol % halothane. Subsequent administration of a muscarinic cholinergic antagonist, atropine sulfate, selectively abolished all type 2 immobility‐related theta field activity, while type 1 movement‐related theta was still intact. At anesthetic levels (1.5–2.0 vol %) in acute experiments, hippocampal field activity spontaneously cycled between theta and large‐amplitude irregular activity. Analysis of depth profiles in four experiments revealed they were identical to those previously described for rats under urethane anesthesia conditions. In addition, the discharge properties of 31 theta‐related cells, classified as tonic and phasic theta‐on and tonic and phasic theta‐off cells, did not differ significantly from those described previously in rats anesthetized with urethane. These data provide further support for an involvement of GABAA receptors in the generation of hippocampal theta. Hippocampus 2003;13:38–47. © 2003 Wiley‐Liss, Inc.

[1]  Christian Rosenmund,et al.  Identification of Differentiation-Associated Brain-Specific Phosphate Transporter as a Second Vesicular Glutamate Transporter (VGLUT2) , 2001, The Journal of Neuroscience.

[2]  R. Traub,et al.  Axo-Axonal Coupling A Novel Mechanism for Ultrafast Neuronal Communication , 2001, Neuron.

[3]  H. Faulkner,et al.  Evidence for a Common Binding Cavity for Three General Anesthetics within the GABAA Receptor , 2001, The Journal of Neuroscience.

[4]  M. MacIver,et al.  Membrane and Synaptic Actions of Halothane on Rat Hippocampal Pyramidal Neurons and Inhibitory Interneurons , 2000, The Journal of Neuroscience.

[5]  J. Burt,et al.  Mechanism and selectivity of the effects of halothane on gap junction channel function. , 2000, Circulation research.

[6]  P. Somogyi,et al.  Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons , 2000, Nature Neuroscience.

[7]  T. Kosaka,et al.  Gap Junctions Linking the Dendritic Network of GABAergic Interneurons in the Hippocampus , 2000, The Journal of Neuroscience.

[8]  S. Hestrin,et al.  A network of fast-spiking cells in the neocortex connected by electrical synapses , 1999, Nature.

[9]  B. Connors,et al.  Two networks of electrically coupled inhibitory neurons in neocortex , 1999, Nature.

[10]  G. Buzsáki,et al.  Interdependence of Multiple Theta Generators in the Hippocampus: a Partial Coherence Analysis , 1999, The Journal of Neuroscience.

[11]  J. Tepper,et al.  Inhibitory control of neostriatal projection neurons by GABAergic interneurons , 1999, Nature Neuroscience.

[12]  Y Yarom,et al.  Electrotonic Coupling Interacts with Intrinsic Properties to Generate Synchronized Activity in Cerebellar Networks of Inhibitory Interneurons , 1999, The Journal of Neuroscience.

[13]  J. Csicsvari,et al.  Oscillatory Coupling of Hippocampal Pyramidal Cells and Interneurons in the Behaving Rat , 1999, The Journal of Neuroscience.

[14]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[15]  F. Skinner,et al.  Slow Oscillations (≤1 Hz) Mediated by GABAergic Interneuronal Networks in Rat Hippocampus , 1998, The Journal of Neuroscience.

[16]  R. Traub,et al.  Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro , 1998, Nature.

[17]  Y. Yaari,et al.  Halothane Blocks Synaptic Excitation of Inhibitory Interneurons , 1996, Anesthesiology.

[18]  R. Traub,et al.  Effects of intravenous anaesthetic agents on fast inhibitory oscillations in the rat hippocampus in vitro , 1996, British journal of pharmacology.

[19]  B. Maciver,et al.  Synaptic Mechanisms of Thiopental‐induced Alterations in Synchronized Cortical Activity , 1996, Anesthesiology.

[20]  R. Traub,et al.  Neuronal networks for induced ‘40 Hz’ rhythms , 1996, Trends in Neurosciences.

[21]  P. Somogyi,et al.  Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons , 1995, Nature.

[22]  R. Traub,et al.  Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation , 1995, Nature.

[23]  W. R. Lieb,et al.  Molecular and cellular mechanisms of general anaesthesia , 1994, Nature.

[24]  B. H. Bland,et al.  Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex , 1993, Progress in Neurobiology.

[25]  J. Konopacki,et al.  Theta-like activity in hippocampal formation slices: cholinergic-GABAergic interaction. , 1993, Neuroreport.

[26]  B. H. Bland,et al.  The extrinsic modulation of hippocampal theta depends on the coactivation of cholinergic and GABA-ergic medial septal inputs , 1992, Neuroscience & Biobehavioral Reviews.

[27]  E. London,et al.  Receptor binding and electrophysiological effects of Dehydroepiandrosterone sulfate, an antagonist of the GABAA receptor , 1991, Neuroscience.

[28]  B. H. Bland,et al.  In vivo intrahippocampal microinfusion of carbachol and bicuculline induces theta‐like oscillations in the septally deafferented hippocampus , 1991, Hippocampus.

[29]  C. Peracchia.  Effects of the anesthetics heptanol, halothane and isoflurane on gap junction conductance in crayfish septate axons: A calcium- and hydrogen-independent phenomenon potentiated by caffeine and theophylline, and inhibited by 4-aminopyridine , 1991, The Journal of Membrane Biology.

[30]  B. H. Bland,et al.  Preliminary observations on the physiology and pharmacology of hippocampal θ-off cells , 1989, Brain Research.

[31]  M. Christie,et al.  Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  Brian H. Bland,et al.  Carbachol-induced EEG ‘theta’ in hippocampal formation slices: evidence for a third generator of theta in CA3c area , 1988, Brain Research.

[33]  B. H. Bland,et al.  State-dependent spike train dynamics of hippocampal formation neurons: evidence for theta-on and theta-off cells , 1987, Brain Research.

[34]  B. H. Bland.  The physiology and pharmacology of hippocampal formation theta rhythms , 1986, Progress in Neurobiology.

[35]  F. H. Lopes da Silva,et al.  Spectral characteristics of the hippocampal EEG in the freely moving rat. , 1982, Electroencephalography and clinical neurophysiology.

[36]  Ian Q. Whishaw,et al.  Generators and topography of hippocampal Theta (RSA) in the anaesthetized and freely moving rat , 1976, Brain Research.

[37]  Jonathan Winson,et al.  Hippocampal theta rhythm. I. Depth profiles in the curarized rat , 1976, Brain Research.

[38]  C. H. Vanderwolf,et al.  Two types of hippocampal rhythmical slow activity in both the rabbit and the rat: Relations to behavior and effects of atropine, diethyl ether, urethane, and pentobarbital , 1975, Experimental Neurology.

[39]  J. B. Ranck,et al.  Localization and anatomical identification of theta and complex spike cells in dorsal hippocampal formation of rats , 1975, Experimental Neurology.

[40]  P. Andersen,et al.  Two generators of hippocampal theta activity in rabbits , 1975, Brain Research.

[41]  C. H. Vanderwolf,et al.  Hippocampal electrical activity and voluntary movement in the rat. , 1969, Electroencephalography and clinical neurophysiology.

[42]  Brian H. Bland,et al.  The medial septum: Node of the ascending brainstem hippocampal synchronizing pathways. , 2000 .

[43]  G. Buzsáki,et al.  Intracellular correlates of hippocampal theta rhythm in identified pyramidal cells, granule cells, and basket cells , 1995, Hippocampus.

[44]  S. Steffensen.  Dehydroepiandrosterone sulfate suppresses hippocampal recurrent inhibition and synchronizes neuronal activity to theta rhythm , 1995, Hippocampus.

[45]  J. Winson,et al.  Patterns of hippocampal theta rhythm in the freely moving rat. , 1974, Electroencephalography and clinical neurophysiology.