Inhibitory interactions between spiny projection neurons in the rat striatum.

The spiny projection neurons are by far the most numerous type of striatal neuron. In addition to being the principal projection neurons of the striatum, the spiny projection neurons also have an extensive network of local axon collaterals by which they make synaptic connections with other striatal projection neurons. However, up to now there has been no direct physiological evidence for functional inhibitory interactions between spiny projection neurons. Here we present new evidence that striatal projection neurons are interconnected by functional inhibitory synapses. To examine the physiological properties of unitary inhibitory postsynaptic potentials (IPSPs), dual intracellular recordings were made from pairs of spiny projection neurons in brain slices of adult rat striatum. Synaptic interactions were found in 9 of 45 pairs of neurons using averages of 200 traces that were triggered by a single presynaptic action potential. In all cases, synaptic interactions were unidirectional, and no bidirectional interactions were detected. Unitary IPSPs evoked by a single presynaptic action potential had a peak amplitude ranging from 157 to 319 microV in different connections (mean: 277 +/- 46 microV, n = 9). The percentage of failures of single action potentials to evoke a unitary IPSP was estimated and ranged from 9 to 63% (mean: 38 +/- 14%, n = 9). Unitary IPSPs were reversibly blocked by bicuculline (n = 4) and had a reversal potential of -62.4 +/- 0.7 mV (n = 5), consistent with GABA-mediated inhibition. The findings of the present study correlate very well with anatomical evidence for local synaptic connectivity between spiny projection neurons and suggest that lateral inhibition plays a significant role in the information processing operations of the striatum.

[1]  C. Marsden.  The mysterious motor function of the basal ganglia , 1982, Neurology.

[2]  G. Akopian,et al.  Short-term plasticity at inhibitory synapses in rat striatum and its effects on striatal output. , 2001, Journal of neurophysiology.

[3]  J. Wickens,et al.  Two dynamic modes of striatal function under dopaminergic‐cholinergic control: Simulation and analysis of a model , 1991, Synapse.

[4]  S. T. Kitai,et al.  Medium spiny neuron projection from the rat striatum: An intracellular horseradish peroxidase study , 1980, Brain Research.

[5]  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.

[6]  W. Schultz,et al.  A neural network model with dopamine-like reinforcement signal that learns a spatial delayed response task , 1999, Neuroscience.

[7]  I. Grofová.  The identification of striatal and pallidal neurons projecting to substantia nigra An experimental study by means of retrograde axonal transport of horseradish peroxidase , 1975, Brain Research.

[8]  J. Deuchars,et al.  Single axon IPSPs elicited in pyramidal cells by three classes of interneurones in slices of rat neocortex. , 1996, The Journal of physiology.

[9]  O. Andreassen,et al.  Estimation of the number of somatostatin neurons in the striatum: An in situ hybridization study using the optical fractionator method , 1996, The Journal of comparative neurology.

[10]  P. Somogyi,et al.  Synaptic connections of enkephalin-immunoreactive nerve terminals in the neostriatum: a correlated light and electron microscopic study , 1982, Journal of neurocytology.

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

[12]  Hagai Bergman,et al.  Stepping out of the box: information processing in the neural networks of the basal ganglia , 2001, Current Opinion in Neurobiology.

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

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

[15]  A. Amos.  A Computational Model of Information Processing in the Frontal Cortex and Basal Ganglia , 2000, Journal of Cognitive Neuroscience.

[16]  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 .

[17]  H. Kita,et al.  GABAergic circuits of the striatum. , 1993, Progress in brain research.

[18]  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.

[19]  G. Radnikow,et al.  Heterogeneity in use-dependent depression of inhibitory postsynaptic potentials in the rat neostriatum in vitro. , 1997, Journal of neurophysiology.

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

[21]  T. Sejnowski,et al.  A Computational Model of How the Basal Ganglia Produce Sequences , 1998, Journal of Cognitive Neuroscience.

[22]  Y. Katayama,et al.  Electrophysiological evidence favoring intracaudate axon collaterals of GABAergic caudate output neurons in the cat , 1981, Brain Research.

[23]  D. Oorschot.  Total number of neurons in the neostriatal, pallidal, subthalamic, and substantia nigral nuclei of the rat basal ganglia: A stereological study using the cavalieri and optical disector methods , 1996, The Journal of comparative neurology.

[24]  M. Lacey,et al.  Subpopulations of GABA-mediated synaptic potentials in slices of rat dorsal striatum are differentially modulated by presynaptic GABAB receptors , 1991, Brain Research.

[25]  H. Markram,et al.  Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. , 1997, The Journal of physiology.

[26]  J. Wickens,et al.  A cellular mechanism of reward-related learning , 2001, Nature.

[27]  G. Hynd,et al.  Attention Deficit- Hyperactivity Disorder and Asymmetry of the Caudate Nucleus , 1993, Journal of child neurology.

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

[29]  J. Tepper,et al.  In vivo studies of the postnatal development of rat neostriatal neurons. , 1993, Progress in brain research.

[30]  A. Sadikot,et al.  GABA promotes survival but not proliferation of parvalbumin-immunoreactive interneurons in rodent neostriatum: an in vivo study with stereology , 2001, Neuroscience.

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

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

[33]  B. D. Bennett,et al.  Characterization of calretinin-immunoreactive structures in the striatum of the rat , 1993, Brain Research.

[34]  G. Arbuthnott,et al.  Computational models of the basal ganglia , 2000, Movement disorders : official journal of the Movement Disorder Society.

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

[36]  T. Kita,et al.  Regenerative potentials in rat neostriatal neurons in an in vitro slice preparation , 2004, Experimental Brain Research.

[37]  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.

[38]  Melburn R. Park,et al.  Recurrent inhibition in the rat neostriatum , 1980, Brain Research.