Auditory sensory gating in hippocampus and reticular thalamic neurons in anesthetized rats

BACKGROUND Auditory gating is thought to reflect sensory information processing and is absent or diminished in schizophrenic patients. Although abnormal thalamic sensory processing has been proposed in schizophrenia, sensory gating of thalamic neurons has not been demonstrated experimentally. The aim of the present study was to establish whether auditory gating is present in the rat thalamus using a well-characterized animal model of auditory gating and schizophrenia. METHODS Hippocampal electroencephalogram and single-unit activity in the thalamic reticular nucleus (nRT) were recorded in anaesthetized rats. Evoked potentials in the hippocampus and neuronal activity in the nRT were monitored in response to bilateral auditory stimuli. The effects of the psychostimulant D-amphetamine and the antipsychotic haloperidol on auditory gating were evaluated. RESULTS Thalamic reticular nucleus neurons showed gated responses to paired-tone auditory stimuli, resembling hippocampal auditory gating. D-amphetamine disrupted auditory gating of nRT neurons and abolished their burst activity. D-amphetamine also disrupted hippocampal auditory gating and induced hippocampal theta activity. The amphetamine-induced gating deficit was reversed by haloperidol in both regions. CONCLUSIONS Our findings provide the first experimental evidence for auditory gating of nRT neurons. We demonstrated that amphetamine disrupts sensory processing of nRT neurons, indicating similarities between hippocampal and thalamic sensory gating. These findings support the presumed connection between dopamine hyperfunction and abnormal thalamic filtering in schizophrenia.

[1]  B. Pakkenberg,et al.  Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. , 1990, Archives of general psychiatry.

[2]  A. C. Cuello,et al.  Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry , 1985, Brain Research.

[3]  P. Bickford,et al.  Auditory sensory gating in the rat hippocampus: modulation by brainstem activity , 1993, Brain Research.

[4]  G. V. Simpson,et al.  Multiple brain systems generating the rat auditory evoked potential. II. Dissociation of auditory cortex and non-lemniscal generator systems , 1993, Brain Research.

[5]  A. Cools,et al.  Hippocampal and cortical sensory gating in rats: effects of quinpirole microinjections in nucleus accumbens core and shell , 2001, Neuroscience.

[6]  J. Luthman,et al.  Effects of neonatal dopamine depletion on sensory inhibition in the rat , 1996, Pharmacology Biochemistry and Behavior.

[7]  R. Guillery,et al.  Paying attention to the thalamic reticular nucleus , 1998, Trends in Neurosciences.

[8]  A. Parent,et al.  Projection from the external pallidum to the reticular thalamic nucleus in the squirrel monkey , 1991, Brain Research.

[9]  J E Skinner,et al.  Selective regulation of thalamic sensory relay nuclei by nucleus reticularis thalami. , 1976, Electroencephalography and clinical neurophysiology.

[10]  L. Swanson.  The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[11]  K. Stevens,et al.  Normalizing Effects of Nicotine and a Novel Nicotinic Agonist on Hippocampal Auditory Gating in Two Animal Models , 1997, Pharmacology Biochemistry and Behavior.

[12]  S. Foote,et al.  Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  P. Bickford,et al.  Phencyclidine and auditory sensory gating in the hippocampus of the rat , 1992, Neuropharmacology.

[14]  T. Wassink,et al.  Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms , 1999, Biological Psychiatry.

[15]  F. Crick.  Function of the thalamic reticular complex: the searchlight hypothesis. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[16]  A Carlsson,et al.  The current status of the dopamine hypothesis of schizophrenia. , 1988, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[17]  A. Shosaku,et al.  Auditory neurons in the rat thalamic reticular nucleus , 2004, Experimental Brain Research.

[18]  Christer Halldin,et al.  PET Mapping of Extrastriatal D2-like Dopamine Receptors in the Human Brain Using an Anatomic Standardization Technique and [11C]FLB 457 , 1999, NeuroImage.

[19]  M S Buchsbaum,et al.  PET and MRI of the thalamus in never-medicated patients with schizophrenia. , 1996, The American journal of psychiatry.

[20]  David A. McCormick,et al.  Acetylcholine induces burst firing in thalamic reticular neurones by activating a potassium conductance , 1986, Nature.

[21]  R. Freedman,et al.  Medial septal neuron activity in relation to an auditory sensory gating paradigm , 1993, Neuroscience.

[22]  W Melega,et al.  Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  J. Palacios,et al.  Differential Visualization of Dopamine D2 and D3 Receptor Sites in Rat Brain. A Comparative Study Using In Situ Hybridization Histochemistry and Ligand Binding Autoradiography , 1993, The European journal of neuroscience.

[24]  J. Edeline,et al.  Characteristics of reliable tone-evoked oscillations in the rat thalamo-cortical auditory system , 2000, Hearing Research.

[25]  James E. Vaughn,et al.  GABA neurons are the major cell type of the nucleus reticularis thalami , 1980, Brain Research.

[26]  R. Croft,et al.  Associations of P50 suppression and desensitization with perceptual and cognitive features of “unreality” in schizotypy , 2001, Biological Psychiatry.

[27]  A. Mcghie,et al.  Disorders of attention and perception in early schizophrenia. , 1961, The British journal of medical psychology.

[28]  D. Rosielle,et al.  Psychiatry , 1905, NeuroImage.

[29]  K. Iwama,et al.  Analysis of recurrent inhibitory circuit in rat thalamus: Neurophysiology of the thalamic reticular nucleus , 1989, Progress in Neurobiology.

[30]  A. Malhotra,et al.  Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R. Llinás,et al.  Electrophysiology of mammalian thalamic neurones in vitro , 1982, Nature.

[32]  P. Fabene,et al.  Neural correlates of sensory gating in the rat: decreased Fos induction in the lateral septum , 2001, Brain Research Bulletin.

[33]  Robert Freedman,et al.  Gating of auditory P50 in schizophrenics: Unique effects of clozapine , 1996, Biological Psychiatry.

[34]  Robert Freedman,et al.  Auditory sensory gating in hippocampal neurons: A model system in the rat , 1990, Biological Psychiatry.

[35]  J. Edeline,et al.  Tone‐evoked oscillations in the rat auditory cortex result from interactions between the thalamus and reticular nucleus , 2000, The European journal of neuroscience.

[36]  E. G. Jones,et al.  Some aspects of the organization of the thalamic reticular complex , 2004, The Journal of comparative neurology.

[37]  Markus Heilig,et al.  Synaptic degeneration in thalamus in schizophrenia , 1996, The Lancet.

[38]  H. Nauta.  Projections of the pallidal complex: An autoradiographic study in the cat , 1979, Neuroscience.

[39]  J. Ehrhardt,et al.  Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. , 1994, Science.

[40]  A. Grace,et al.  Modulation of dorsal thalamic cell activity by the ventral pallidum: Its role in the regulation of thalamocortical activity by the basal ganglia , 1994, Synapse.

[41]  M. Geyer,et al.  Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. , 1998, The American journal of psychiatry.

[42]  G. Rose,et al.  Neurophysiological studies of sensory gating in rats: Effects of amphetamine, phencyclidine, and haloperidol , 1986, Biological Psychiatry.

[43]  R. Vertes,et al.  Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. , 1997, Neuroscience.

[44]  N. Swerdlow,et al.  Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens , 2005, Psychopharmacology.

[45]  M. Laruelle,et al.  Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies , 1999, Journal of psychopharmacology.

[46]  A. Parent,et al.  Projections of brainstem core cholinergic and non-cholinergic neurons of cat to intralaminar and reticular thalamic nuclei , 1988, Neuroscience.

[47]  S. Haber,et al.  Organization of the output of the ventral striatopallidal system in the rat: Ventral pallidal efferents , 1993, Neuroscience.

[48]  Donald J Woodward,et al.  Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats , 1999, Brain Research.

[49]  H. Sackeim,et al.  Amphetamine disrupts P50 suppression in normal subjects , 1999, Biological Psychiatry.

[50]  Charles L. Cox,et al.  Glutamate Inhibits Thalamic Reticular Neurons , 1999, The Journal of Neuroscience.

[51]  W. Nauta,et al.  Efferent connections of the ventral pallidum: Evidence of a dual striato pallidofugal pathway , 1985, The Journal of comparative neurology.

[52]  U. Schridde,et al.  The role of hippocampal theta activity in sensory gating in the rat , 2001, Physiology & Behavior.

[53]  T Sharma,et al.  Magnetic resonance imaging of the thalamus in first-episode psychosis. , 2001, The American journal of psychiatry.

[54]  Thierry Bal,et al.  Sensory gating mechanisms of the thalamus , 1994, Current Opinion in Neurobiology.

[55]  J. Yamamoto.  Roles of cholinergic, dopaminergic, noradrenergic, serotonergic and GABAergic systems in changes of the EEG power spectra and behavioral states in rabbits. , 1988, Japanese journal of pharmacology.

[56]  D. Sibley,et al.  D2 dopamine receptor distribution in the rodent CNS using anti-peptide antisera , 1993, Brain Research.

[57]  R. Dingledine,et al.  Brain stem stimulation and the acetylcholine‐evoked inhibition of neurones in the feline nucleus reticularis thalami , 1977, The Journal of physiology.

[58]  R. V. Van Heertum,et al.  Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[59]  S. Snyder,et al.  Amphetamine psychosis: a "model" schizophrenia mediated by catecholamines. , 1973, The American journal of psychiatry.

[60]  D L Braff,et al.  Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder. , 2000, The American journal of psychiatry.

[61]  P. Venables,et al.  INPUT DYSFUNCTION IN SCHIZOPHRENIA. , 1964, Progress in experimental personality research.

[62]  Dennis S. Charney,et al.  Neurobiology of Mental Illness , 2004 .

[63]  A Carlsson,et al.  A Paradigm Shift in Brain Research , 2001, Science.

[64]  M. Deschenes,et al.  Muscarinic inhibition of reticular thalamic cells by basal forebrain neurones. , 1992, Neuroreport.

[65]  R Freedman,et al.  Schizophrenia, sensory gating, and nicotinic receptors. , 1998, Schizophrenia bulletin.

[66]  J. Joyce,et al.  Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat, cat, and human in relation to tyrosine hydroxylase‐immunoreactive fibers , 1994, Hippocampus.

[67]  J. Krystal,et al.  Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. , 1996, Proceedings of the National Academy of Sciences of the United States of America.