Muscarinic Regulation of Dendritic and Axonal Outputs of Rat Thalamic Interneurons: A New Cellular Mechanism for Uncoupling Distal Dendrites

Inhibition is crucial for sharpening the sensory information relayed through the thalamus. To understand how the interneuron-mediated inhibition in the thalamus is regulated, we studied the muscarinic effects on interneurons in the lateral posterior nucleus and lateral geniculate nucleus of the thalamus. Here, we report that activation of muscarinic receptors switched the firing pattern in thalamic interneurons from bursting to tonic. Although neuromodulators switch the firing mode in several other types of neurons by altering their membrane potential, we found that activation of muscarinic subtype 2 receptors switched the fire mode in thalamic interneurons by selectively decreasing their input resistance. This is attributable to the muscarinic enhancement of a hyperpolarizing potassium conductance and two depolarizing cation conductances. The decrease in input resistance appeared to electrotonically uncouple the distal dendrites of thalamic interneurons, which effectively changed the inhibition pattern in thalamocortical cells. These results suggest a novel cellular mechanism for the cholinergic transformation of long-range, slow dendrite- and axon-originated inhibition into short-range, fast dendrite-originated inhibition in the thalamus observed in vivo. It is concluded that the electrotonic properties of the dendritic compartments of thalamic interneurons can be dynamically regulated by muscarinic activity.

[1]  W Singer,et al.  Cholinergic mechanisms in the reticular control of transmission in the cat lateral geniculate nucleus. , 1988, Journal of neurophysiology.

[2]  Bert Sakmann,et al.  Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons , 1995, Neuron.

[3]  J. Huguenard,et al.  Reciprocal inhibitory connections and network synchrony in the mammalian thalamus. , 1999, Science.

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

[5]  J. Zhu,et al.  Recurrent inhibitory interneurons of the Rabbit's lateral posterior-pulvinar complex. , 1997, Journal of neurophysiology.

[6]  H. Ralston.  Evidence for Presynaptic Dendrites and a Proposal for their Mechanism of Action , 1971, Nature.

[7]  R. Malinow,et al.  Calcium-Evoked Dendritic Exocytosis in Cultured Hippocampal Neurons. Part I: Trans-Golgi Network-Derived Organelles Undergo Regulated Exocytosis , 1998, The Journal of Neuroscience.

[8]  D. McCormick,et al.  Role of the ferret perigeniculate nucleus in the generation of synchronized oscillations in vitro. , 1995, The Journal of physiology.

[9]  A. Sefton,et al.  Mode of termination of afferents from the thalamic reticular nucleus in the dorsal lateral geniculate nucleus of the rat , 1980, Brain Research.

[10]  P Heggelund,et al.  Response variability of single cells in the dorsal lateral geniculate nucleus of the cat. Comparison with retinal input and effect of brain stem stimulation. , 1994, Journal of neurophysiology.

[11]  G. Shepherd,et al.  Analysis of Relations between NMDA Receptors and GABA Release at Olfactory Bulb Reciprocal Synapses , 2000, Neuron.

[12]  David A. McCormick,et al.  Acetylcholine inhibits identified interneurons in the cat lateral geniculate nucleus , 1988, Nature.

[13]  B. Connors,et al.  Sensory experience modifies the short-term dynamics of neocortical synapses , 1999, Nature.

[14]  R.,et al.  Low-Threshold Calcium Currents in Central Nervous System Neurons , 2003 .

[15]  G Oakson,et al.  Different cellular types in mesopontine cholinergic nuclei related to ponto-geniculo-occipital waves , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  J. Zhu,et al.  Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity , 2000, Nature Neuroscience.

[17]  M. Carandini,et al.  Orientation tuning of input conductance, excitation, and inhibition in cat primary visual cortex. , 2000, Journal of neurophysiology.

[18]  P. C. Murphy,et al.  Effects of brain stem parabrachial activation on receptive field properties of cells in the cat's lateral geniculate nucleus. , 1995, Journal of neurophysiology.

[19]  D. Prince,et al.  Clonazepam suppresses GABAB-mediated inhibition in thalamic relay neurons through effects in nucleus reticularis. , 1994, Journal of neurophysiology.

[20]  D. Paré,et al.  Various types of inhibitory postsynaptic potentials in anterior thalamic cells are differentially altered by stimulation of laterodorsal tegmental cholinergic nucleus , 1992, Neuroscience.

[21]  Stephen R. Williams,et al.  Electrophysiological and morphological properties of interneurones in the rat dorsal lateral geniculate nucleus in vitro. , 1996, The Journal of physiology.

[22]  B. Sakmann,et al.  A new cellular mechanism for coupling inputs arriving at different cortical layers , 1999, Nature.

[23]  D. Ferster,et al.  EPSP-IPSP interactions in cat visual cortex studied with in vivo whole- cell patch recording , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  David A. McCormick,et al.  Modulation of a pacemaker current through Ca2+-induced stimulation of cAMP production , 1999, Nature Neuroscience.

[25]  M. Bickford,et al.  Location of muscarinic type 2 receptors within the synaptic circuitry of the cat visual thalamus , 1999, The Journal of comparative neurology.

[26]  G. Ahlsén,et al.  Inhibition from the brain stem of inhibitory interneurones of the cat's dorsal lateral geniculate nucleus. , 1984, The Journal of physiology.

[27]  D. Contreras,et al.  Synchronization of fast (30-40 Hz) spontaneous oscillations in intrathalamic and thalamocortical networks , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  R. Guillery,et al.  Functional organization of thalamocortical relays. , 1996, Journal of neurophysiology.

[29]  M. Stewart,et al.  A quantitative investigation of the neuronal composition of the rat dorsal lateral geniculate nucleus using GABA-immunocytochemistry , 1986, Neuroscience.

[30]  Brain stem modulation of spatial receptive field properties of single cells in the dorsal lateral geniculate nucleus of the cat. , 1993, Journal of neurophysiology.

[31]  A. Sillito,et al.  The cholinergic influence on the function of the cat dorsal lateral geniculate nucleus (dLGN) , 1983, Brain Research.

[32]  M. Deschenes,et al.  Electrophysiology of neurons of lateral thalamic nuclei in cat: resting properties and burst discharges. , 1984, Journal of neurophysiology.

[33]  Charles L. Cox,et al.  Glutamate locally activates dendritic outputs of thalamic interneurons , 1998, Nature.

[34]  P. C. Murphy,et al.  Brain-stem modulation of the response properties of cells in the cat's perigeniculate nucleus , 1994, Visual Neuroscience.

[35]  S. Hunt,et al.  Neural elements containing glutamic acid decarboxylase (GAD) in the dorsal lateral geniculate nucleus of the rat; Immunohistochemical studies by light and electron microscopy , 1983, Neuroscience.

[36]  H. Pape,et al.  Postnatal expression pattern of calcium-binding proteins in organotypic thalamic cultures and in the dorsal thalamus in vivo. , 1998, Brain research. Developmental brain research.

[37]  K J Staley,et al.  Membrane properties of dentate gyrus granule cells: comparison of sharp microelectrode and whole-cell recordings. , 1992, Journal of neurophysiology.

[38]  J. Storm-Mathisen,et al.  Glutamate‐ and GABA‐containing neurons in the mouse and rat brain, as demonstrated with a new immunocytochemical technique , 1984, The Journal of comparative neurology.

[39]  J. Lechleiter,et al.  Subcellular patterns of calcium release determined by G protein-specific residues of muscarinic receptors , 1991, Nature.

[40]  A. Reyes,et al.  Three GABA Receptor-Mediated Postsynaptic Potentials in Interneurons in the Rat Lateral Geniculate Nucleus , 1999, The Journal of Neuroscience.

[41]  G. Westbrook,et al.  Regulation of synaptic timing in the olfactory bulb by an A-type potassium current , 1999, Nature Neuroscience.

[42]  D. McCormick,et al.  Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro. , 1995, The Journal of physiology.

[43]  W W Lytton,et al.  An intrinsic oscillation in interneurons of the rat lateral geniculate nucleus. , 1999, Journal of neurophysiology.

[44]  Maria V. Sanchez-Vives,et al.  Functional dynamics of GABAergic inhibition in the thalamus. , 1997, Science.

[45]  J. Zhu,et al.  Cellular mechanisms underlying two muscarinic receptor-mediated depolarizing responses in relay cells of the rat lateral geniculate nucleus , 1998, Neuroscience.

[46]  B. Connors,et al.  Two networks of electrically coupled inhibitory neurons in neocortex , 1999, Nature.

[47]  M. Pirchio,et al.  Cl‐ ‐ and K+‐dependent inhibitory postsynaptic potentials evoked by interneurones of the rat lateral geniculate nucleus. , 1988, The Journal of physiology.

[48]  D. A. McCormick,et al.  Electrophysiological and pharmacological properties of interneurons in the cat dorsal lateral geniculate nucleus , 1995, Neuroscience.

[49]  D. McCormick.  Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity , 1992, Progress in Neurobiology.

[50]  D. Paré,et al.  Three types of inhibitory postsynaptic potentials generated by interneurons in the anterior thalamic complex of cat. , 1991, Journal of neurophysiology.

[51]  S. Sherman,et al.  Dendritic current flow in relay cells and interneurons of the cat's lateral geniculate nucleus. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[52]  B. Connors,et al.  Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor‐mediated responses in neocortex of rat and cat. , 1988, The Journal of physiology.

[53]  J. Bolz,et al.  Formation of specific afferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[54]  B H Gähwiler,et al.  Selective glutamate receptor antagonists can induce or prevent axonal sprouting in rat hippocampal slice cultures. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[55]  W. W. Lytton,et al.  Burst firing in identified rat geniculate interneurons , 1999, Neuroscience.

[56]  Z. Kisvárday,et al.  Prevention of Ca(2+)‐mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current. , 1994, The Journal of physiology.

[57]  J J Zhu,et al.  Control of recurrent inhibition of the lateral posterior-pulvinar complex by afferents from the deep layers of the superior colliculus of the rabbit. , 1998, Journal of neurophysiology.

[58]  H C Pape,et al.  Excitatory and differential disinhibitory actions of acetylcholine in the lateral geniculate nucleus of the cat. , 1986, The Journal of physiology.

[59]  S. Sherman,et al.  Control of Dendritic Outputs of Inhibitory Interneurons in the Lateral Geniculate Nucleus , 2000, Neuron.

[60]  David A. McCormick,et al.  Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[61]  T. Sejnowski,et al.  G protein activation kinetics and spillover of gamma-aminobutyric acid may account for differences between inhibitory responses in the hippocampus and thalamus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[62]  D. Prince,et al.  Cholinergic switching within neocortical inhibitory networks. , 1998, Science.

[63]  J. Zhu,et al.  Nicotinic receptor-mediated responses in relay cells and interneurons in the rat lateral geniculate nucleus , 1997, Neuroscience.

[64]  N. Hagiwara,et al.  Modulation by intracellular Ca2+ of the hyperpolarization‐activated inward current in rabbit single sino‐atrial node cells. , 1989, The Journal of physiology.

[65]  M. Descheˆnes,et al.  The effects of brainstem peribrachial stimulation on neurons of the lateral geniculate nucleus , 1989, Neuroscience.

[66]  A. Michel,et al.  On the interaction of gallamine with muscarinic receptor subtypes. , 1990, European journal of pharmacology.

[67]  J. Zhu,et al.  Recurrent inhibitory circuitry in the deep layers of the rabbit superior colliculus , 2000, The Journal of physiology.

[68]  B. Sakmann,et al.  Dendritic GABA Release Depresses Excitatory Transmission between Layer 2/3 Pyramidal and Bitufted Neurons in Rat Neocortex , 1999, Neuron.

[69]  J. Zhu,et al.  Properties of a hyperpolarization-activated cation current in interneurons in the rat lateral geniculate nucleus , 1999, Neuroscience.

[70]  J. Zhu,et al.  Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1 and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites , 2000, The Journal of physiology.

[71]  D. Uhlrich,et al.  Muscarinic receptor subtypes in the lateral geniculate nucleus: A light and electron microscopic analysis , 1999, The Journal of comparative neurology.

[72]  B. Connors,et al.  Differential Regulation of Neocortical Synapses by Neuromodulators and Activity , 1997, Neuron.

[73]  B. Sakmann,et al.  Ca2+ buffering and action potential-evoked Ca2+ signaling in dendrites of pyramidal neurons. , 1996, Biophysical journal.