Dopamine Selectively Inhibits the Direct Cortical Pathway to the CA1 Hippocampal Region

The perforant path input (pp) is a major direct source of specific sensory information for the CA1 hippocampal region. The termination area of this pathway, the stratum lacunosum-moleculare, has the highest concentration of dopamine receptors in the hippocampus. We have examined the properties of the pp input and its modulation by dopamine. The input is glutamatergic and has a larger NMDA component than the Schaffer collateral (sc) input. Dopamine strongly inhibits the response to pp stimulation (IC50 ∼3 μm) but not the response to sc stimulation. Dopamine reduces both the NMDA and AMPA components of transmission at the pp and increases paired-pulse facilitation. In the sc, the NMDA component but not the AMPA component is decreased, and paired-pulse facilitation is not affected. The effect of dopamine on the pp does not depend on GABAA inhibition but is reduced by the antagonists of both D1 and D2 families of dopamine receptors. The effect is not completely blocked by the combination of D1 and D2 antagonists, but is completely blocked by the atypical neuroleptic clozapine. Our results provide the first evidence for strong dopaminergic control of transmission in the perforant path. By inhibiting this pathway, dopamine hyperfunction and/or NMDA hypofunction abnormalities implicated in schizophrenia may isolate CA1 from its main source of sensory information.

[1]  R. Lubow.  Latent inhibition. , 1973, Psychological bulletin.

[2]  O. Vinogradova.  Functional Organization of the Limbic System in the Process of Registration of Information: Facts and Hypotheses , 1975 .

[3]  J. Nadler,et al.  Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice. , 1982, The Journal of pharmacology and experimental therapeutics.

[4]  F. F. Weight,et al.  Perforant pathway activation of hippocampal CA1 stratum pyramidale neurons: Electrophysiological evidence for a direct pathway , 1982, Brain Research.

[5]  P. Calabresi,et al.  Dopaminergic and noradrenergic responses in the hippocampal slice preparation Evidence for different receptors , 1984, Neuropharmacology.

[6]  V. Gribkoff,et al.  Modulation by dopamine of population responses and cell membrane properties of hippocampal CA1 neurons in vitro , 1984, Brain Research.

[7]  S. Pockett.  Dopamine changes the shape of action potentials in hippocampal pyramidal cells , 1985, Brain Research.

[8]  R. Nicoll,et al.  Dopamine decreases the calcium-activated afterhyperpolarization in hippocampal CA1 pyramidal cells , 1986, Brain Research.

[9]  Gordon H. Bower,et al.  Computational models of learning in simple neural systems , 1989 .

[10]  G. Buzsáki.  Two-stage model of memory trace formation: A role for “noisy” brain states , 1989, Neuroscience.

[11]  W. Levy.  A computational approach to hippocampal function , 1989 .

[12]  P. Greengard,et al.  Inhibition by dopamine of (Na+ + K+)ATPase activity in neostriatal neurons through D1 and D2 dopamine receptor synergism , 1990, Nature.

[13]  M. Yeckel,et al.  Feedforward excitation of the hippocampus by afferents from the entorhinal cortex: redefinition of the role of the trisynaptic pathway. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  F. H. Lopes da Silva,et al.  Anatomic organization and physiology of the limbic cortex. , 1990, Physiological reviews.

[15]  M. Packard,et al.  Dissociation of hippocampus and caudate nucleus memory systems by posttraining intracerebral injection of dopamine agonists. , 1991, Behavioral neuroscience.

[16]  M. Martres,et al.  Dopamine activation of the arachidonic acid cascade as a basis for D1D2 receptor synergism , 1991, Nature.

[17]  Eric R. Marsh,et al.  Do Central Antiadrenergic Actions Contribute to the Atypical Properties of Clozapine? , 1992, British Journal of Psychiatry.

[18]  B. Bunney.  Clozapine: A Hypothesised Mechanism for its Unique Clinical Profile , 1992, British Journal of Psychiatry.

[19]  P. Calabresi,et al.  Coactivation of D1 and D2 dopamine receptors is required for long-term synaptic depression in the striatum , 1992, Neuroscience Letters.

[20]  W B Levy,et al.  Electrophysiological and pharmacological characterization of perforant path synapses in CA1: mediation by glutamate receptors. , 1992, Journal of neurophysiology.

[21]  B. McNaughton,et al.  Computational approaches to hippocampal function , 1992, Current Biology.

[22]  Coward Dm,et al.  General pharmacology of clozapine. , 1992 .

[23]  D. Coward,et al.  General Pharmacology of Clozapine , 1992, British Journal of Psychiatry.

[24]  M. LeMay,et al.  Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. , 1992, The New England journal of medicine.

[25]  D. Surmeier,et al.  D1 and D2 dopamine receptor modulation of sodium and potassium currents in rat neostriatal neurons. , 1993, Progress in brain research.

[26]  M. Sasa,et al.  A mechanism underlying dopamine D1 and D2 receptor‐mediated inhibition of dopaminergic neurones in the ventral tegmental area in vitro , 1993, British journal of pharmacology.

[27]  John O'Keefe,et al.  Hippocampus, theta, and spatial memory , 1993, Current Opinion in Neurobiology.

[28]  Enhancement of D2 receptor agonist‐induced inhibition by D1 receptor agonist in the ventral tegmental area , 1993, British journal of pharmacology.

[29]  E. Kandel,et al.  Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. , 1993, Science.

[30]  M. Hasselmo,et al.  Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  B. Turetsky,et al.  Frontal and temporal lobe brain volumes in schizophrenia: relationship to symptomatology and clinical subtype , 1994, Biological Psychiatry.

[32]  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.

[33]  H. Fibiger,et al.  The potent and selective dopamine D1 receptor agonist A-77636 increases cortical and hippocampal acetylcholine release in the rat. , 1994, European journal of pharmacology.

[34]  H. Meltzer,et al.  An overview of the mechanism of action of clozapine. , 1994, The Journal of clinical psychiatry.

[35]  L. Aguayo,et al.  Dopamine inhibits a sustained calcium current through activation of alpha adrenergic receptors and a GTP-binding protein in adult rat sympathetic neurons. , 1994, The Journal of pharmacology and experimental therapeutics.

[36]  J. Gray,et al.  Latent inhibition in drug naive schizophrenics: relationship to duration of illness and dopamine D2 binding using SPET , 1995, Schizophrenia Research.

[37]  Jeffrey A. Lieberman,et al.  Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia , 1995, Schizophrenia Research.

[38]  R I Grossman,et al.  Frontal and temporal lobe brain volumes in schizophrenia. Relationship to symptoms and clinical subtype. , 1995, Archives of general psychiatry.

[39]  J. Olney,et al.  Glutamate receptor dysfunction and schizophrenia. , 1995, Archives of general psychiatry.

[40]  A. Halberstadt.  The phencyclidine-glutamate model of schizophrenia. , 1995, Clinical neuropharmacology.

[41]  R. Empson,et al.  Perforant path connections to area CA1 are predominantly inhibitory in the rat hippocampal‐entorhinal cortex combined slice preparation , 1995, Hippocampus.

[42]  A. Carlsson.  Neurocircuitries and neurotransmitter interactions in schizophrenia , 1995, International clinical psychopharmacology.

[43]  G. Fein,et al.  Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: A 31Phosphorous magnetic resonance spectroscopic imaging study , 1995, Biological Psychiatry.

[44]  R. Quirion,et al.  Local modulation of hippocampal acetylcholine release by dopamine D1 receptors: a combined receptor autoradiography and in vivo dialysis study , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  William B. Levy,et al.  Another network model bites the dust: Entorhinal inputs are no more than weakly excitatory in the hippocampal CA1 region , 1995, Hippocampus.

[46]  K. Takenouchi,et al.  Shortening of the hippocampal formation in first‐episode schizophrenic patients , 1995, Psychiatry and clinical neurosciences.

[47]  M. Buchsbaum,et al.  Structural and functional correlates of subsyndromes in chronic schizophrenia. , 1995, Psychopathology.

[48]  P. Somogyi,et al.  High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus , 1995, Neuroscience.

[49]  Richard S. J. Frackowiak,et al.  A functional neuroanatomy of hallucinations in schizophrenia , 1995, Nature.

[50]  C. Gerfen,et al.  D1–D2 dopamine receptor synergy in striatum: effects of intrastriatal infusions of dopamine agonists and antagonists on immediate early gene expression , 1995, Neuroscience.

[51]  J. Gorman,et al.  Reality monitoring failure in schizophrenia: The role of selective attention , 1996, Schizophrenia Research.

[52]  J. Lisman,et al.  D1/D5 Dopamine Receptor Activation Increases the Magnitude of Early Long-Term Potentiation at CA1 Hippocampal Synapses , 1996, The Journal of Neuroscience.

[53]  K. Hsu,et al.  Characterization of dopamine receptors mediating inhibition of excitatory synaptic transmission in the rat hippocampal slice. , 1996, Journal of neurophysiology.

[54]  É. Hajós‐Korcsok,et al.  8-OH-DPAT-induced release of hippocampal noradrenaline in vivo: evidence for a role of both 5-HT1A and dopamine D1 receptors. , 1996, European journal of pharmacology.

[55]  S. Sesack,et al.  Hippocampal afferents to the rat prefrontal cortex: Synaptic targets and relation to dopamine terminals , 1996, The Journal of comparative neurology.

[56]  Glutamate receptors and schizophrenia: opportunities and caveats. , 1996 .

[57]  P. Perruchet,et al.  Implicit and explicit associative memory in patients with schizophrenia , 1996, Schizophrenia Research.

[58]  M. Munetz.  Contemporary Issues in the Treatment of Schizophrenia , 1996 .

[59]  P. Goldman-Rakic,et al.  Localization of dopamine D4 receptors in GABAergic neurons of the primate brain , 1996, Nature.

[60]  T. Kaneko,et al.  Pre- and postsynaptic localization of a metabotropic glutamate receptor, mGluR2, in the rat brain: an immunohistochemical study with a monoclonal antibody , 1996, Neuroscience Letters.

[61]  N. Swerdlow,et al.  Do D1/D2 Interactions Regulate Prepulse Inhibition in Rats? , 1996, Neuropsychopharmacology.

[62]  J. Lisman,et al.  Physiologically realistic formation of autoassociative memory in networks with theta/gamma oscillations: role of fast NMDA channels. , 1996, Learning & memory.

[63]  J. Brioni,et al.  Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat , 1996, Neuroscience.

[64]  D. Javitt.  Glutamate receptors and schizophrenia: opportunities and caveats. , 1996, Molecular psychiatry.

[65]  O. Pongs,et al.  Distribution of high-conductance Ca(2+)-activated K+ channels in rat brain: targeting to axons and nerve terminals , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[66]  B. Bunney,et al.  D1–D2 Interaction in Feedback Control of Midbrain Dopamine Neurons , 1997, The Journal of Neuroscience.

[67]  M. Smith,et al.  Substituted 4-aminopiperidines having high in vitro affinity and selectivity for the cloned human dopamine D4 receptor. , 1997, European journal of pharmacology.

[68]  R. Hampson,et al.  The significance of neural ensemble codes during behavior and cognition. , 1997, Annual review of neuroscience.

[69]  F. J. White,et al.  Dopamine enhances glutamate-induced excitation of rat striatal neurons by cooperative activation of D1 and D2 class receptors , 1997, Neuroscience Letters.

[70]  M. Millan,et al.  Noradrenaline and adrenaline are high affinity agonists at dopamine D4 receptors. , 1997, European journal of pharmacology.

[71]  E. Malchiodi,et al.  Distribution of D4 dopamine receptor in rat brain with sequence-specific antibodies. , 1997, Brain research. Molecular brain research.

[72]  H Eichenbaum,et al.  Declarative memory: insights from cognitive neurobiology. , 1997, Annual review of psychology.

[73]  I Izquierdo,et al.  Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[74]  S. Sesack,et al.  Ultrastructural immunocytochemical localization of the dopamine D2 receptor within GABAergic neurons of the rat striatum , 1997, Brain Research.

[75]  R. Bernabeu,et al.  Involvement of hippocampal D1/D5 receptor-cAMP signaling pathways in a late memory consolidation phase of an aversively-motivated task in rats , 1997 .

[76]  J. Meador-Woodruff,et al.  Linking the Family of D2 Receptors to Neuronal Circuits in Human Brain: Insights into Schizophrenia , 1997, Neuropsychopharmacology.

[77]  F. H. Lopes da Silva,et al.  Nucleus Reuniens Thalami Modulates Activity in Hippocampal Field CA1 through Excitatory and Inhibitory Mechanisms , 1997, The Journal of Neuroscience.

[78]  Andreas Lüthi,et al.  Modulation of AMPA receptor unitary conductance by synaptic activity , 1998, Nature.

[79]  S. Sesack,et al.  Dopamine axons in primate prefrontal cortex: specificity of distribution, synaptic targets, and development. , 1998, Advances in pharmacology.

[80]  J. Lisman,et al.  D1/D5 Dopamine Receptors Inhibit Depotentiation at CA1 Synapses via cAMP-Dependent Mechanism , 1998, The Journal of Neuroscience.

[81]  G. Barrionuevo,et al.  Electrophysiological and pharmacological characterization of the direct perforant path input to hippocampal area CA3. , 1998, Journal of neurophysiology.

[82]  N. Alpert,et al.  Impaired recruitment of the hippocampus during conscious recollection in schizophrenia , 1998, Nature Neuroscience.