Properties and Plasticity of Excitatory Synapses on Dopaminergic and GABAergic Cells in the Ventral Tegmental Area

Excitatory inputs to the ventral tegmental area (VTA) influence the activity of both dopaminergic (DA) and GABAergic (GABA) cells, yet little is known about the basic properties of excitatory synapses on these two cell types. Using a midbrain slice preparation and whole-cell recording techniques, we found that excitatory synapses on DA and GABA cells display several differences. Synapses on DA cells exhibit a depression in response to repetitive activation, are minimally affected by the GABAB receptor agonist baclofen, and express NMDA receptor-dependent long-term potentiation (LTP). In contrast, synapses on GABA cells exhibit a facilitation in response to repetitive activation, are depressed significantly by baclofen, and do not express LTP. The relative contribution of NMDA and non-NMDA receptors to the synaptic currents recorded from the two cell types is the same as is the depression of synaptic transmission elicited by the application of adenosine, serotonin, or methionine enkephalin (met-enkephalin). The significant differences in the manner in which excitatory synaptic inputs to DA and GABA cells in the VTA can be modulated have potentially important implications for understanding the behavior of VTA neurons during normal behavior and during pathological states such as addiction.

[1]  J. B. Ranck,et al.  Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. II. Hippocampal slow waves and theta cell firing during bar pressing and other behaviors. , 1973, Experimental neurology.

[2]  W. Chambers,et al.  Reflexes involving triceps surae from the ankle joint of the cat. , 1973, Experimental neurology.

[3]  J. B. Ranck,et al.  Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. , 1973, Experimental neurology.

[4]  J. O’Keefe Place units in the hippocampus of the freely moving rat , 1976, Experimental Neurology.

[5]  S. Langer,et al.  Presynaptic receptors , 1978, Nature.

[6]  T. Bliss,et al.  Synaptic plasticity in the hippocampus , 1979, Trends in Neurosciences.

[7]  M. J. Christie,et al.  Excitotoxin lesions suggest an aspartatergic projection from rat medial prefrontal cortex to ventral tegmental area , 1985, Brain Research.

[8]  M. J. Christie,et al.  Excitatory amino acid projections to the nucleus accumbens septi in the rat: A retrograde transport study utilizingd[3H]aspartate and [3H]GABA , 1987, Neuroscience.

[9]  H. Kita,et al.  Efferent projections of the subthalamic nucleus in the rat: Light and electron microscopic analysis with the PHA‐L method , 1987, The Journal of comparative neurology.

[10]  P. Duffy,et al.  Regulation of the mesocorticolimbic dopamine system by glutamic acid receptor subtypes. , 1989, The Journal of pharmacology and experimental therapeutics.

[11]  A. Grace,et al.  Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  N. Mercuri,et al.  Two cell types in rat substantia nigra zona compacta distinguished by membrane properties and the actions of dopamine and opioids , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  P. Verbanck,et al.  Evidence for the presence of N-methyl-d-aspartate receptors in the ventral tegmental area of the rat: an electrophysiological in vitro study , 1990, Brain Research.

[14]  R. Tsien,et al.  Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices , 1990, Nature.

[15]  Kim Cooper,et al.  Low access resistance perforated patch recordings using amphotericin B , 1991, Journal of Neuroscience Methods.

[16]  E. Costa,et al.  Glutamate receptor subtypes mediate excitatory synaptic currents of dopamine neurons in midbrain slices , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  S. A. Turkanis,et al.  DNQX blockade of amphetamine behavioral sensitization , 1991, Brain Research.

[18]  H. Haas,et al.  The electrophysiology of adenosine in the mammalian central nervous system , 1991, Progress in Neurobiology.

[19]  S. Sesack,et al.  Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area , 1992, The Journal of comparative neurology.

[20]  R. North,et al.  Two types of neurone in the rat ventral tegmental area and their synaptic inputs. , 1992, The Journal of physiology.

[21]  D. Johnston,et al.  NMDA-receptor-independent long-term potentiation. , 1992, Annual review of physiology.

[22]  M. Scanziani,et al.  Presynaptic inhibition in the hippocampus , 1993, Trends in Neurosciences.

[23]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[24]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[25]  P. Kalivas Neurotransmitter regulation of dopamine neurons in the ventral tegmental area , 1993, Brain Research Reviews.

[26]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[27]  G. Collingridge,et al.  Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors , 1993, Nature.

[28]  E. French,et al.  Electrophysiological evidence for the existence of NMDA and non‐NMDA receptors on rat ventral tegmental dopamine neurons , 1993, Synapse.

[29]  S. Schenk,et al.  Sensitization to cocaine's motor activating properties produced by electrical kindling of the medial prefrontal cortex but not of the hippocampus , 1994, Brain Research.

[30]  J. Williams,et al.  Cocaine inhibits GABA release in the VTA through endogenous 5-HT , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  Robert C. Malenka,et al.  Synaptic plasticity in the hippocampus: LTP and LTD , 1994, Cell.

[32]  E. French,et al.  NMDA, kainate, and AMPA depolarize nondopamine neurons in the rat ventral tegmentum , 1995, Brain Research Bulletin.

[33]  E. V. Bockstaele,et al.  GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain , 1995, Brain Research.

[34]  M. Reith,et al.  The role of serotonin in the actions of psychostimulants: molecular and pharmacological analyses , 1995, Behavioural Brain Research.

[35]  J. Williams,et al.  Opioid Receptors and the Regulation of Ion Conductances , 1995, Reviews in the neurosciences.

[36]  R. Nicoll,et al.  Contrasting properties of two forms of long-term potentiation in the hippocampus , 1995, Nature.

[37]  M M Merzenich,et al.  Temporal information transformed into a spatial code by a neural network with realistic properties , 1995, Science.

[38]  F. J. White,et al.  Synaptic regulation of mesocorticolimbic dopamine neurons. , 1996, Annual review of neuroscience.

[39]  C. McBain,et al.  Long-Term Potentiation in Distinct Subtypes of Hippocampal Nonpyramidal Neurons , 1996, The Journal of Neuroscience.

[40]  T. Robbins,et al.  Neurobehavioural mechanisms of reward and motivation , 1996, Current Opinion in Neurobiology.

[41]  C. Stevens,et al.  Heterogeneity of Release Probability, Facilitation, and Depletion at Central Synapses , 1997, Neuron.

[42]  G. Koob,et al.  The Neurobiology of Addiction , 1997, Alcohol health and research world.

[43]  J. Williams,et al.  A subset of ventral tegmental area neurons is inhibited by dopamine, 5-hydroxytryptamine and opioids , 1997, Neuroscience.

[44]  P. Overton,et al.  Burst firing in midbrain dopaminergic neurons , 1997, Brain Research Reviews.

[45]  G F Koob,et al.  Drug abuse: hedonic homeostatic dysregulation. , 1997, Science.

[46]  Ann Marie Craig,et al.  Activity Regulates the Synaptic Localization of the NMDA Receptor in Hippocampal Neurons , 1997, Neuron.

[47]  R. Nicoll,et al.  Postsynaptically Silent Synapses in Single Neuron Cultures , 1998, Neuron.

[48]  Peter Somogyi,et al.  Cell Type and Pathway Dependence of Synaptic AMPA Receptor Number and Variability in the Hippocampus , 1998, Neuron.

[49]  K. Tóth,et al.  Target-specific expression of presynaptic mossy fiber plasticity. , 1998, Science.

[50]  B. Gähwiler,et al.  Target cell-specific modulation of transmitter release at terminals from a single axon. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[51]  R. Nicoll,et al.  Development of excitatory circuitry in the hippocampus. , 1998, Journal of neurophysiology.

[52]  S. Henriksen,et al.  Electrophysiological Characterization of GABAergic Neurons in the Ventral Tegmental Area , 1998, The Journal of Neuroscience.

[53]  P. Overton,et al.  Alterations in excitatory amino acid‐mediated regulation of midbrain dopaminergic neurones induced by chronic psychostimulant administration and stress: relevance to behavioural sensitization and drug addiction , 1998, Addiction biology.

[54]  H. Markram,et al.  Differential signaling via the same axon of neocortical pyramidal neurons. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[55]  M. Wolf,et al.  The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants , 1998, Progress in Neurobiology.

[56]  J. Deuchars,et al.  CA1 pyramidal to basket and bistratified cell EPSPs: dual intracellular recordings in rat hippocampal slices , 1998, The Journal of physiology.

[57]  P. Somogyi,et al.  Target-cell-specific facilitation and depression in neocortical circuits , 1998, Nature Neuroscience.

[58]  Richard L. Huganir,et al.  Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons , 1999, Nature Neuroscience.

[59]  J. Partridge,et al.  Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses , 1999, Nature Neuroscience.