Substance P Mediates Excitatory Interactions between Striatal Projection Neurons

The striatum is the largest nucleus of the basal ganglia, and is crucially involved in motor control. Striatal projection cells are medium-size spiny neurons (MSNs) and form functional GABAergic synapses with other MSNs through their axon collaterals. A subpopulation of MSNs also release substance P (SP), but its role in MSN–MSN communication is unknown. We studied this issue in rat brain slices, in the presence of antagonists for GABA, acetylcholine, dopamine, and opioid receptors; under these conditions, whole-cell paired recordings from MSNs (located <100 μm apart) revealed that, in 31/137 (23%) pairs, a burst of five spikes in a MSN caused significant facilitation (14.2 ± 8.9%) of evoked glutamatergic responses in the other MSN. Reciprocal facilitation of glutamatergic responses was present in 4 of these pairs. These facilitatory effects were maximal when spikes preceded glutamatergic responses by 100 ms, and were completely blocked by the NK1 receptor antagonist L-732,138. Furthermore, in 31/57 (54%) MSNs, a burst of 5 antidromic stimuli delivered to MSN axons in the globus pallidus significantly potentiated glutamatergic responses evoked 250 or 500 ms later by stimulation of the corpus callosum. These effects were larger at 250 than 500 ms intervals, were completely blocked by L-732,138, and facilitated spike generation. These data demonstrate that MSNs facilitate glutamatergic inputs to neighboring MSNs through spike-released SP acting on NK1 receptors. The current view that MSNs form inhibitory networks characterized by competitive dynamics will have to be updated to incorporate the fact that groups of MSNs interact in an excitatory manner.

[1]  Y. Kubota,et al.  Dependence of GABAergic Synaptic Areas on the Interneuron Type and Target Size , 2000, The Journal of Neuroscience.

[2]  Y. Kawaguchi,et al.  Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  Roy M. Smeal,et al.  A rat brain slice preparation for characterizing both thalamostriatal and corticostriatal afferents , 2007, Journal of Neuroscience Methods.

[4]  A. D. Smith,et al.  Synaptic Connections Between Spiny Neurons of the Direct and Indirect Pathways in the Neostriatum of the Rat: Evidence from Dopamine Receptor and Neuropeptide Immunostaining , 1996, The European journal of neuroscience.

[5]  Charles J. Wilson,et al.  Comparison of IPSCs Evoked by Spiny and Fast-Spiking Neurons in the Neostriatum , 2004, The Journal of Neuroscience.

[6]  G. Somjen,et al.  Conditions for the triggering of spreading depression studied with computer simulations. , 2002, Journal of neurophysiology.

[7]  Jeffery R Wickens,et al.  Inhibitory interactions between spiny projection neurons in the rat striatum. , 2002, Journal of neurophysiology.

[8]  Enrico Bracci,et al.  Cholinergic Interneurons Control the Excitatory Input to the Striatum , 2007, The Journal of Neuroscience.

[9]  Charles J. Wilson,et al.  Feedforward and feedback inhibition in neostriatal GABAergic spiny neurons , 2008, Brain Research Reviews.

[10]  Y. Smith,et al.  Cortical inputs to m2‐immunoreactive striatal interneurons in rat and monkey , 2000, Synapse.

[11]  David A McCormick,et al.  Cortical and subcortical generators of normal and abnormal rhythmicity. , 2002, International review of neurobiology.

[12]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[13]  J. Penney,et al.  The functional anatomy of disorders of the basal ganglia , 1995, Trends in Neurosciences.

[14]  A. Graybiel.  Building action repertoires: memory and learning functions of the basal ganglia , 1995, Current Opinion in Neurobiology.

[15]  R. North,et al.  Membrane properties and synaptic responses of rat striatal neurones in vitro. , 1991, The Journal of physiology.

[16]  Charles J. Wilson,et al.  Effect of subthreshold up and down states on the whisker-evoked response in somatosensory cortex. , 2004, Journal of neurophysiology.

[17]  Charles J. Wilson,et al.  Surround inhibition among projection neurons is weak or nonexistent in the rat neostriatum. , 1994, Journal of neurophysiology.

[18]  A M Graybiel,et al.  Cortically Driven Immediate-Early Gene Expression Reflects Modular Influence of Sensorimotor Cortex on Identified Striatal Neurons in the Squirrel Monkey , 1997, The Journal of Neuroscience.

[19]  T. Kita,et al.  Effects of 4-aminopyridine (4-AP) on rat neostriatal neurons in an in vitro slice preparation , 1985, Brain Research.

[20]  P. Redgrave,et al.  The basal ganglia: a vertebrate solution to the selection problem? , 1999, Neuroscience.

[21]  C. Wilson,et al.  Potassium currents responsible for inward and outward rectification in rat neostriatal spiny projection neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  P. Goldman-Rakic.  The corticostriatal fiber system in the rhesus monkey: organization and development. , 1983, Progress in brain research.

[23]  P. Nieto,et al.  Tachykinins and tachykinin receptors: structure and activity relationships. , 2004, Current medicinal chemistry.

[24]  W. Singer,et al.  Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties , 1989, Nature.

[25]  Charles J. Wilson,et al.  Cholinergic interneuron characteristics and nicotinic properties in the striatum. , 2002, Journal of neurobiology.

[26]  Charles J. Wilson,et al.  Regulation of action-potential firing in spiny neurons of the rat neostriatum in vivo. , 1998, Journal of neurophysiology.

[27]  T. Kita,et al.  Passive electrical membrane properties of rat neostriatal neurons in an in vitro slice preparation , 1984, Brain Research.

[28]  Antoine Depaulis,et al.  Endogenous control of epilepsy: The nigral inhibitory system , 1994, Progress in Neurobiology.

[29]  J. Bargas,et al.  Dopaminergic Modulation of Axon Collaterals Interconnecting Spiny Neurons of the Rat Striatum , 2003, The Journal of Neuroscience.

[30]  J. Jefferys,et al.  On the Synchronizing Mechanisms of Tetanically Induced Hippocampal Oscillations , 1999, The Journal of Neuroscience.

[31]  Charles J. Wilson,et al.  Membrane potential synchrony of simultaneously recorded striatal spiny neurons in vivo , 1998, Nature.

[32]  Charles J. Wilson,et al.  Fine structure and synaptic connections of the common spiny neuron of the rat neostriatum: A study employing intracellular injection of horseradish peroxidase , 1980 .

[33]  M. Avoli,et al.  Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro , 2002, Progress in Neurobiology.

[34]  Charles J. Wilson,et al.  Contribution of a slowly inactivating potassium current to the transition to firing of neostriatal spiny projection neurons. , 1994, Journal of neurophysiology.

[35]  Henry H. Yin,et al.  Dopaminergic Control of Corticostriatal Long-Term Synaptic Depression in Medium Spiny Neurons Is Mediated by Cholinergic Interneurons , 2006, Neuron.

[36]  Martin J. McKeown,et al.  When Do Epileptic Seizures Really Begin? , 2001, Neuron.

[37]  M. Low,et al.  Facilitated glutamatergic transmission in the striatum of D2 dopamine receptor-deficient mice. , 2001, Journal of neurophysiology.

[38]  R. Andrew,et al.  Spreading depression: imaging and blockade in the rat neocortical brain slice. , 2002, Journal of neurophysiology.

[39]  T. Aosaki,et al.  Roles of μ-Opioid Receptors in GABAergic Synaptic Transmission in the Striosome and Matrix Compartments of the Striatum , 2008, Molecular Neurobiology.

[40]  B. Connors,et al.  Intrinsic firing patterns of diverse neocortical neurons , 1990, Trends in Neurosciences.

[41]  Charles J. Wilson,et al.  Connectivity and Convergence of Single Corticostriatal Axons , 1998, The Journal of Neuroscience.

[42]  D. Surmeier,et al.  Dichotomous Anatomical Properties of Adult Striatal Medium Spiny Neurons , 2008, The Journal of Neuroscience.

[43]  Jeffery R Wickens,et al.  Simulation of GABA function in the basal ganglia: computational models of GABAergic mechanisms in basal ganglia function. , 2007, Progress in brain research.

[44]  Charles J. Wilson,et al.  The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  M. Nicolelis,et al.  Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system. , 1995, Science.

[46]  M. Steriade,et al.  Neocortical very fast oscillations (ripples, 80-200 Hz) during seizures: intracellular correlates. , 2003, Journal of neurophysiology.

[47]  J. Bargas,et al.  Patterns of excitatory and inhibitory synaptic transmission in the rat neostriatum as revealed by 4-AP. , 1994, Journal of neurophysiology.

[48]  K. Gale,et al.  Subcortical structures and pathways involved in convulsive seizure generation. , 1992, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[49]  M. Iadarola,et al.  Substantia nigra: site of anticonvulsant activity mediated by gamma-aminobutyric acid. , 1982, Science.

[50]  Charles J. Wilson,et al.  GABAergic microcircuits in the neostriatum , 2004, Trends in Neurosciences.

[51]  Luc Defebvre,et al.  Relationship between oscillations in the basal ganglia and synchronization of cortical activity. , 2002, Epileptic disorders : international epilepsy journal with videotape.

[52]  J. Bolam,et al.  The postsynaptic targets of substance P-immunoreactive terminals in the rat neostriatum with particular reference to identified spiny striatonigral neurons , 2004, Experimental Brain Research.

[53]  H. Bergman,et al.  Information processing, dimensionality reduction and reinforcement learning in the basal ganglia , 2003, Progress in Neurobiology.

[54]  D. Plenz.  When inhibition goes incognito: feedback interaction between spiny projection neurons in striatal function , 2003, Trends in Neurosciences.

[55]  Enrico Bracci,et al.  Dopamine excites fast-spiking interneurons in the striatum. , 2002, Journal of neurophysiology.

[56]  P. Calabresi,et al.  Physiological role of GABAb receptors in the mammalian neostriatum. , 1992, Advances in biochemical psychopharmacology.

[57]  C. Wilson,et al.  Intracellular recording of identified neostriatal patch and matrix spiny cells in a slice preparation preserving cortical inputs. , 1989, Journal of neurophysiology.

[58]  Carlos Cepeda,et al.  Transient and Progressive Electrophysiological Alterations in the Corticostriatal Pathway in a Mouse Model of Huntington's Disease , 2003, The Journal of Neuroscience.

[59]  P. Greengard,et al.  Dopamine and cAMP-Regulated Phosphoprotein 32 kDa Controls Both Striatal Long-Term Depression and Long-Term Potentiation, Opposing Forms of Synaptic Plasticity , 2000, The Journal of Neuroscience.

[60]  P. Schwindt,et al.  Quantitative analysis of firing properties of pyramidal neurons from layer 5 of rat sensorimotor cortex. , 1997, Journal of neurophysiology.

[61]  J. Penney,et al.  Differential expression of mGluR5 metabotropic glutamate receptor mRNA by rat striatal neurons , 1995, The Journal of comparative neurology.

[62]  J. Wickens,et al.  Actions of adenosine A 2A receptors on synaptic connections of spiny projection neurons in the neostriatal inhibitory network. , 2008, Journal of neurophysiology.

[63]  J. McNamara,et al.  Activation of substantia nigra neurons: role in the propagation of seizures in kindled rats , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[64]  L. Vercueil,et al.  Seizures and the basal ganglia: a review of the clinical data. , 2002, Epileptic disorders : international epilepsy journal with videotape.

[65]  C. Gerfen.  The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. , 1992, Annual review of neuroscience.

[66]  J. Wickens,et al.  Dopamine reverses the depression of rat corticostriatal synapses which normally follows high-frequency stimulation of cortex In vitro , 1996, Neuroscience.

[67]  Antonio Pisani,et al.  Metabotropic glutamate receptors and striatal synaptic plasticity: implications for neurological diseases , 2004, Progress in Neurobiology.

[68]  Enrico Bracci,et al.  Voltage‐dependent membrane potential oscillations of rat striatal fast‐spiking interneurons , 2003, The Journal of physiology.

[69]  Charles J. Wilson.  GABAergic inhibition in the neostriatum. , 2007, Progress in brain research.

[70]  R. Traub,et al.  Are there unifying principles underlying the generation of epileptic afterdischarges in vitro? , 1994, Progress in brain research.

[71]  Antonio Pisani,et al.  Acetylcholine-mediated modulation of striatal function , 2000, Trends in Neurosciences.

[72]  R. North,et al.  Pre- and postsynaptic inhibition by opioids in rat striatum , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[73]  T. Sejnowski,et al.  Thalamocortical oscillations in the sleeping and aroused brain. , 1993, Science.

[74]  Charles J. Wilson,et al.  Intrinsic Membrane Properties Underlying Spontaneous Tonic Firing in Neostriatal Cholinergic Interneurons , 2000, The Journal of Neuroscience.

[75]  Florin Amzica,et al.  Neuronal and Glial Membrane Potentials during Sleep and Paroxysmal Oscillations in the Neocortex , 2000, The Journal of Neuroscience.

[76]  J. Houk,et al.  Model of cortical-basal ganglionic processing: encoding the serial order of sensory events. , 1998, Journal of neurophysiology.

[77]  J. Deniau,et al.  Synaptic Convergence of Motor and Somatosensory Cortical Afferents onto GABAergic Interneurons in the Rat Striatum , 2002, Journal of Neuroscience.

[78]  M. Croning,et al.  Action of adenosine receptor antagonists on hypoxia‐induced effects in the rat hippocampus in vitro , 1995, British journal of pharmacology.

[79]  C. Wilson,et al.  Origins of post synaptic potentials evoked in spiny neostriatal projection neurons by thalamic stimulation in the rat , 2004, Experimental Brain Research.

[80]  P. Calabresi,et al.  Engagement of rat striatal neurons by cortical epileptiform activity investigated with paired recordings. , 2004, Journal of neurophysiology.

[81]  P. Goldman-Rakic,et al.  Presynaptic and postsynaptic subcellular localization of substance P receptor immunoreactivity in the neostriatum of the rat and rhesus monkey (Macaca mulatta) , 1996, The Journal of comparative neurology.

[82]  Luis Carrillo-Reid,et al.  Different inhibitory inputs onto neostriatal projection neurons as revealed by field stimulation. , 2005, Journal of neurophysiology.

[83]  J. Bolam,et al.  Input from the frontal cortex and the parafascicular nucleus to cholinergic interneurons in the dorsal striatum of the rat , 1992, Neuroscience.

[84]  A. Crossman.  Functional anatomy of movement disorders , 2000, Journal of anatomy.

[85]  P. Somogyi,et al.  Monosynaptic cortical input and local axon collaterals of identified striatonigral neurons. A light and electron microscopic study using the golgi‐peroxidase transport‐degeneration procedure , 1981, The Journal of comparative neurology.

[86]  P. Groves,et al.  Fine structure and synaptic connections of the common spiny neuron of the rat neostriatum: a study employing intracellular inject of horseradish peroxidase. , 1980, The Journal of comparative neurology.

[87]  Charles J. Wilson,et al.  Move to the rhythm: oscillations in the subthalamic nucleus–external globus pallidus network , 2002, Trends in Neurosciences.

[88]  Charles J. Wilson,et al.  Spontaneous subthreshold membrane potential fluctuations and action potential variability of rat corticostriatal and striatal neurons in vivo. , 1997, Journal of neurophysiology.

[89]  J. Bolam,et al.  Synaptic organisation of the basal ganglia , 2000, Journal of anatomy.

[90]  P. Apicella.  Tonically active neurons in the primate striatum and their role in the processing of information about motivationally relevant events , 2002, The European journal of neuroscience.

[91]  Charles L. Wilson,et al.  High‐frequency oscillations in human brain , 1999, Hippocampus.

[92]  J. Wickens,et al.  Computational models of the basal ganglia: from robots to membranes , 2004, Trends in Neurosciences.

[93]  C. Gerfen.  The neostriatal mosaic: multiple levels of compartmental organization , 1992, Trends in Neurosciences.

[94]  Charles J. Wilson,et al.  The generation of natural firing patterns in neostriatal neurons. , 1993, Progress in brain research.

[95]  E. Bracci,et al.  Substance P depolarizes striatal projection neurons and facilitates their glutamatergic inputs , 2008, The Journal of physiology.

[96]  M. Steriade,et al.  Spontaneous and artificial activation of neocortical seizures. , 1999, Journal of neurophysiology.

[97]  Martin Lévesque,et al.  Organization of the basal ganglia: the importance of axonal collateralization , 2000, Trends in Neurosciences.

[98]  P. Calabresi,et al.  The corticostriatal projection: from synaptic plasticity to dysfunctions of the basal ganglia , 1996, Trends in Neurosciences.

[99]  G. Somjen.  Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. , 2001, Physiological reviews.

[100]  S. T. Kitai,et al.  Firing patterns and synaptic potentials of identified giant aspiny interneurons in the rat neostriatum , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[101]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[102]  G. Graveland,et al.  The frequency and distribution of medium-sized neurons with indented nuclei in the primate and rodent neostriatum , 1985, Brain Research.

[103]  A M Graybiel,et al.  The basal ganglia and adaptive motor control. , 1994, Science.

[104]  M. Szente,et al.  Stimulation of substantia nigra pars reticulata suppresses neocortical seizures , 1992, Brain Research.

[105]  Paolo Calabresi,et al.  Dopamine-mediated regulation of corticostriatal synaptic plasticity , 2007, Trends in Neurosciences.

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

[107]  G. Baranauskas,et al.  An NK1 Receptor‐dependent Component of the Slow Excitation Recorded Intracellularly from Rat Motoneurons Following Dorsal Root Stimulation , 1995, The European journal of neuroscience.

[108]  I. Tarnawa,et al.  Comparison of spontaneous and evoked epileptiform activity in three in vitro epilepsy models , 2002, Brain Research.

[109]  C.J. Wilson,et al.  Morphology and synaptic connections of crossed corticostriatal neurons in the rat , 1987, The Journal of comparative neurology.

[110]  K. A. Yamada,et al.  Developmental characteristics of epileptiform activity in immature rat neocortex: a comparison of four in vitro seizure models. , 2001, Brain research. Developmental brain research.

[111]  Paolo Calabresi,et al.  Electrophysiology of dopamine in normal and denervated striatal neurons , 2000, Trends in Neurosciences.

[112]  U. Heinemann,et al.  Epileptiform discharges induced by combined application of bicuculline and 4-aminopyridine are resistant to standard anticonvulsants in slices of rats , 1999, Neuroscience Letters.

[113]  C. Steinhäuser,et al.  Ion channels in glial cells , 2000, Brain Research Reviews.

[114]  B. Connors,et al.  Two dynamically distinct inhibitory networks in layer 4 of the neocortex. , 2003, Journal of neurophysiology.