Pedunculopontine tegmental nucleus-induced inhibition of muscle activity in the rat

The connections of the pedunculopontine tegmental nucleus (PPN) have led us to propose that this structure mediates striatally induced inhibition of muscle activity by directing basal ganglia output to an inhibitory reticulospinal system (nucleus reticularis gigantocellularis and ventralis, nrGi-V). We conducted experiments in order to examine the effects of electrical stimulation of the PPN on the activity of selected neck and shoulder muscles. PPN stimulation at low rates (0.1 Hz) elicited bilateral muscle excitation. As the rate of stimulation was increased (e.g. to 10 Hz), less excitation was observed. Anodal DC current inactivation of the nrGi-V during concurrent 10 Hz PPN stimulation resulted in an augmentation of muscle activity above the levels observed during 10 Hz PPN stimulation alone. PPN stimulation (10 Hz) also profoundly inhibited cortically-induced muscle activity. Further support for our proposal stems from increased baseline activity (0.1 Hz PPN-induced excitation) in animals with ibotenic acid lesions of the PPN as compared to normal animals. Apparently, destruction of the PPN releases the musculature from tonic and/or phasic inhibition. A model is discussed which attempts to account for both the rate-dependent changes in excitation and the inhibition of cortically induced muscle activity.

[1]  The nucleus tegmenti pedunculopontinus and circling behaviour in the rat , 1981, Neuroscience Letters.

[2]  W. A. McGovern,et al.  A Study in Experimental Tremor (Part 1 of 2) , 1962 .

[3]  C. Saper,et al.  Pedunculopontine tegmental nucleus of the rat: Cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum , 1987, The Journal of comparative neurology.

[4]  M. Mesulam,et al.  Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6) , 1983, Neuroscience.

[5]  Possible descending pathways mediating spontaneous tremor in monkeys. , 1984, Advances in neurology.

[6]  A. C. Cuello,et al.  Cholinergic projections from the midbrain and pons to the thalamus in the rat, identified by combined retrograde tracing and choline acetyltransferase immunohistochemistry , 1985, Brain Research.

[7]  W. Nauta,et al.  Efferent connections of the substantia nigra and ventral tegmental area in the rat , 1979, Brain Research.

[8]  B W Peterson,et al.  Reticulospinal projections to spinal motor nuclei. , 1979, Annual review of physiology.

[9]  R. Spencer,et al.  A cholinergic projection to the rat substantia nigra from the pedunculopontine tegmental nucleus , 1987, Brain Research.

[10]  E. J. Tehovnik,et al.  Circling elicited from the anteromedial cortex and medial pons: refractory periods and summation , 1987, Brain Research.

[11]  F. Mettler,et al.  RÔLE OF THE NEOSTRIATUM , 1941 .

[12]  H. Magoun.  BULBAR INHIBITION AND FACILITATION OF MOTOR ACTIVITY. , 1944, Science.

[13]  M. Herkenham.  The afferent and efferent connections of the ventromedial thalamic nucleus in the rat , 1979, The Journal of comparative neurology.

[14]  Jeffrey T. Keller,et al.  Connections of the subthalamic nucleus in the monkey , 1981, Brain Research.

[15]  P. Slater,et al.  Effects of lesions in some basal ganglia nuclei and efferent projections on tremorine-induced limb rigidity in rats , 1983, Experimental Neurology.

[16]  J. Delgado.  Inhibitory Functions in the Neostriatum , 1979 .

[17]  E. Scarnati,et al.  Pedunculopontine-evoked excitation of substantia nigra neurons in the rat , 1984, Brain Research.

[18]  H. Mclennan,et al.  SOME BEHAVIORAL EFFECTS OF STIMULATION OF THE CAUDATE NUCLEUS IN UNRESTRAINED CATS. , 1964, Canadian journal of physiology and pharmacology.

[19]  H. Kimura,et al.  The central cholinergic system studied by choline acetyltransferase immunohistochemistry in the cat , 1981, The Journal of comparative neurology.

[20]  A M Graybiel,et al.  Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Larry L. Butcher,et al.  Cholinergic systems in the rat brain: III. Projections from the pontomesencephalic tegmentum to the thalamus, tectum, basal ganglia, and basal forebrain , 1986, Brain Research Bulletin.

[22]  C. Hammond,et al.  Anatomical and electrophysiological studies on the reciprocal projections between the subthalamic nucleus and nucleus tegmenti pedunculopontinus in the rat , 1983, Neuroscience.

[23]  Y. Lamarre.  Animal models of physiological, essential and parkinsonian-like tremors , 1984 .

[24]  M. Filion,et al.  Pallidal neurons branching to the thalamus and to the midbrain in the monkey , 1980, Brain Research.

[25]  Robert Hodes,et al.  Influence of the forebrain on somato‐motor activity. II. Facilitation , , 1951, The Journal of comparative neurology.

[26]  C. Gerfen,et al.  Crossed connections of the substantia nigra in the rat , 1982, The Journal of comparative neurology.

[27]  L. Jordan,et al.  Excitatory and inhibitory postsynaptic potentials in alpha-motoneurons produced during fictive locomotion by stimulation of the mesencephalic locomotor region. , 1985, Journal of neurophysiology.

[28]  W. Chambers,et al.  Control of posture by reticular formation and cerebellum in the intract, anesthetized and unanesthetized and in the decerebrated cat. , 1953, The American journal of physiology.

[29]  J. W. Papez.  A summary of fiber connections of the basal ganglia with each other and with other portions of the brain , 1942 .

[30]  R. Hawkins,et al.  Mapping midbrain sites for circling using current-frequency trade off data , 1984, Physiology & Behavior.

[31]  V. J. Wilson,et al.  Comparison of effects of stimulation of Deiters' nucleus and medial longitudinal fasciculus on neck, forelimb, and hindlimb motoneurons. , 1969, Journal of neurophysiology.

[32]  J. Folkerts,et al.  Tremor on stimulation of the midbrain tegmentum. , 1953, Confinia neurologica.

[33]  H. M. Sinnamon,et al.  Forelimb and hindlimb stepping by the anesthetized rat elicited by electrical stimulation of the pons and medulla , 1984, Physiology & Behavior.

[34]  E. Culler,et al.  THE EXTRAPYRAMIDAL SYSTEM: AN EXPERIMENTAL DEMONSTRATION OF FUNCTION , 1939 .

[35]  M. Carpenter,et al.  Efferent fibers of the subthalamic nucleus in the monkey. A comparison of the efferent projections of the subthalamic nucleus, substantia nigra and globus pallidus. , 1967, The American journal of anatomy.

[36]  D. Price,et al.  Loss of pedunculopontine neurons in progressive supranuclear palsy , 1987, Annals of neurology.

[37]  D. Price,et al.  Modulation of cortical and pyramidal tract induced motor responses by electrical stimulation of the basal ganglia , 1975, Brain Research.

[38]  J. Olney,et al.  Kainic acid: a powerful neurotoxic analogue of glutamate. , 1974, Brain research.

[39]  A. Jackson,et al.  Nucleus tegmenti pedunculopontinus: Efferent connections with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport of horseradish peroxidase , 1983, Neuroscience.

[40]  J. Yeomans,et al.  Longitudinal brainstem axons mediating circling: Behavioral measurement of conduction velocity distributions , 1985, Behavioural Brain Research.

[41]  L. Poirier.  Experimental and histological study of midbrain dyskinesias. , 1960, Journal of neurophysiology.

[42]  Usunoff Kg.  Tegmentonigral projection in the cat: electron microscopic observations. , 1984 .

[43]  H. Nauta,et al.  Efferent projections of the subthalamic nucleus: An autoradiographic study in monkey and cat , 1978, The Journal of comparative neurology.

[44]  W. W. Kaelber.  TREMOR AT REST FROM TEGMENTAL LESIONS IN THE CAT , 1963, Journal of neuropathology and experimental neurology.

[45]  C. Pycock.  Turning behaviour in animals , 1980, Neuroscience.

[46]  B. Gernandt,et al.  Reciprocal effects upon spinal motoneurons from stimulation of bulbar reticular formation. , 1955, Journal of neurophysiology.

[47]  V. J. Wilson,et al.  Vestibulospinal and reticulospinal effects on hindlimb, forelimb, and neck alpha motoneurons of the cat. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[48]  W. Nauta,et al.  Projections of the lentiform nucleus in the monkey. , 1966, Brain research.

[49]  J. Penney,et al.  Speculations on the functional anatomy of basal ganglia disorders. , 1983, Annual review of neuroscience.

[50]  C. Terzuolo,et al.  MECHANISMS OF SUPRASPINAL ACTIONS UPON SPINAL CORD ACTIVITIES. RETICULAR INHIBITORY MECHANISMS ON ALPHA-EXTENSOR MOTONEURONS. , 1964, Journal of neurophysiology.

[51]  D. Hommer,et al.  Innervation of substantia nigra neurons by cholinergic afferents from pedunculopontine nucleus in the rat: neuroanatomical and electrophysiological evidence , 1987, Neuroscience.

[52]  Mitsuo Yoshida,et al.  Activation of mesencephalic dopamine neurons by chemical stimulation of the nucleus tegmenti pedunculopontinus pars compacta , 1988, Brain Research.

[53]  A. Proia,et al.  The reciprocal electrophysiological influence between the nucleus tegmenti pedunculopontinus and the substantia nigra in normal and decorticated rats , 1987, Brain Research.

[54]  M. Kelland,et al.  Inhibition and excitation of neck and shoulder muscles during unilateral electrical stimulation of the rat neostriatum , 1988, Behavioural Brain Research.

[55]  A M Graybiel,et al.  The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus, pars compacta , 1983, The Journal of comparative neurology.

[56]  H. Magoun,et al.  An inhibitory mechanism in the bulbar reticular formation. , 1946, Journal of neurophysiology.

[57]  A. Jackson,et al.  Basal ganglia and other afferent projections to the peribrachial region in the rat: A study using retrograde and anterograde transport of horseradish peroxidase , 1981, Neuroscience.

[58]  R. Boucher,et al.  Stereotaxic lesions and movement disorders in monkeys. , 1975, Advances in neurology.

[59]  D. Kooy,et al.  The organization of the efferent projections and striatal afferents of the entopeduncular nucleus and adjacent areas in the rat , 1981, Brain Research.

[60]  N. Mizuno,et al.  Direct projections from the pedunculopontine tegmental nucleus to the subthalamic nucleus in the cat , 1980, Brain Research.

[61]  C. Saper,et al.  Medullary and spinal efferents of the pedunculopontine tegmental nucleus and adjacent mesopontine tegmentum in the rat , 1988, The Journal of comparative neurology.

[62]  W. McCulloch,et al.  A cortico-bulbo-reticular pathway from area 4-s. , 1946, Journal of neurophysiology.

[63]  E. Garcia-Rill,et al.  The mesencephalic locomotor region (MLR) in the rat , 1984, Brain Research.

[64]  Y. Lamarre,et al.  Tremorgenic mechanisms in primates. , 1975, Advances in neurology.

[65]  E. Garcia-Rill,et al.  Connections of the mesencephalic locomotor region (MLR) I. Substantia nigra afferents , 1983, Brain Research Bulletin.

[66]  E. Garcia-Rill,et al.  Connections of the mesencephalic locomotor region (MLR) II. Afferents and efferents , 1983, Brain Research Bulletin.

[67]  M. Carpenter,et al.  Projections of the globus pallidus and adjacent structures: An autoradiographic study in the monkey , 1976, The Journal of comparative neurology.

[68]  Barry W Peterson,et al.  2 – The Reticulospinal System and Its Role in the Control of Movement , 1984 .

[69]  A. Jackson,et al.  Subthalamic projection to nucleus tegmenti pedunculopontinus in the rat , 1981, Neuroscience Letters.

[70]  Clifford B. Saper,et al.  Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry , 1982, Brain Research.

[71]  T. Hattori,et al.  Organization and efferent projections of nucleus tegmenti pedunculopontinus pars compacta with special reference to its cholinergic aspects , 1984, Neuroscience.

[72]  G. Paxinos.  The Rat nervous system , 1985 .

[73]  D. G. Lawrence,et al.  Cortical projections to the red nucleus and the brain stem in the Rhesus monkey. , 1967, Brain research.

[74]  G. Mogenson,et al.  Association of the mesencephalic locomotor region with locomotor activity induced by injections of amphetamine into the nucleus accumbens , 1985, Brain Research.

[75]  A. Levey,et al.  Cholinergic vs. noncholinergic efferents from the mesopontine tegmentum to the extrapyramidal motor system nuclei , 1988, The Journal of comparative neurology.