Summary
The nature of the synaptic transmitter involved in the excitatory fibers linking the nucleus tegmenti pedunculopontinus (PPN) to the pars compacta of the substantia nigra (SNPC) was investigated using microiontophoretic techniques in rats anesthetized with ketamine. Among the SNPC cells activated orthodromically by PPN electrical stimulation, only a few cells were weakly excited by iontophoretically administered acetylcholine (Ach) while most were not affected. Conversely all cells were promptly and powerfully excited by short pulses of glutamate (GLU). The administration of the GLU antagonists glutamic acid diethylester (GDEE) and D-α-aminoadipic acid (DAA) reversibly and simultaneously suppressed both the PPN-evoked orthodromic response and the GLU-induced excitation of SNPC cells without affecting their response to iontophoretic Ach. GDEE was more effective than DAA in counteracting the synaptically evoked excitation. On the other hand, atropine, while antagonizing the Ach response in those cells which were cholinoceptive, did not affect either the PPN-evoked or the GLU-induced excitation. Hence, despite the presence of cholinergic cells in the PPN region, Ach does not appear to be involved in the excitatory PPNSNPC pathway. The present findings suggest that the excitatory PPN fibers innervating the SNPC may utilize GLU or a closely related amino acid as a neurotransmitter.
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References
Aghajanian GK, Bunney BS (1974) Dopaminergic and nondopaminergic neurons of the substantia nigra: differential responses to putative transmitters. Proc IX CINP Congress Excerpta Medica, Amsterdam, pp 444–452
Albe-Fessard D, Stutinky F, Libouban S (1971) Atlas stéréotaxique du rat blanc. Edition CNRS, Paris
Andén NE, Carlsson A, Dahlstrom A, Fuxe K, Hillarp NA, Larsson K (1964) Demonstration and mapping out of nigroneostriatal dopamine neurons. Life Sci 3: 523–530
Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetic, ketamine and phencyclidine, selectively reduces excitation of central mammalian neurones by N-methylaspartate. Br J Pharmacol 79: 565–575
Carter CJ (1982) Topographical distribution of possible glutamatergic pathways from the frontal cortex to the striatum and substantia nigra in rats. Neuropharmacology 21: 379–383
Chéramy A, Leviel V, Glowinski J (1981) Dendritic release of dopamine in the substantia nigra. Nature 289: 537–542
Collingridge GL, Davies J (1981) The influence of striatal stimulation and putative neurotransmitters of identified neurons in the rat substantia nigra. Brain Res 212: 345–349
Davies J, Evans RH, Francis AA, Watkins JC (1979) Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system. J Physiol (Paris) 5: 641–644
DeLong MR, Crutcher MD, Georgopoulos P (1983) Relations between movement and single cell discharge in the substantia nigra of the behaving monkey. J Neurosci 3: 1599–1606
Dray A, Gonye TJ, Oakley NR (1976) Caudate stimulation and substantia nigra activity in the rat. J Physiol (Lond) 259: 825–849
Dray A, Davies J, Oakley NR, Tongroach P, Vellucci S (1978) The dorsal and medial raphe projections to the substantia nigra in the rat: electrophysiological, biochemical and behavioural observations. Brain Res 151: 431–442
Dray A, Oakley NR (1978) Projections from the nucleus accumbens to globus pallidus and substantia nigra in the rat. Experientia 34: 68–70
Evans RH, Watkins JC (1981) Pharmacological antagonists of excitant amino acid action. Life Sci 28: 1303–1308
Fegér J, Ohye C (1975) The unitary activity of the substantia nigra following stimulation of the striatum in the awake monkey. Brain Res 89: 155–159
Feltz P (1971) γ-aminobutyric acid and a caudate-nigral inhibition. Can J Physiol Pharmacol 49: 1113–1115
Fonnum F, Soreide A, Kvale I, Walker J, Walaas I (1981) Glutamate in corticofugal fibres. In: Di Chiara G, Gessa GL (eds) Glutamate as a neurotransmitter. Raven Press, New York, pp 29–41
Frigyesi TL, Purpura DP (1967) Electrophysiological analysis of reciprocal caudate-nigral relations. Brain Res 6: 440–456
Gonya-Magee T, Anderson ME (1983) An electrophysiological characterization of projections from the pedunculopontine area to entopeduncular nucleus and globus pallidus in the cat. Exp Brain Res 49: 269–279
Guyenet PG, Aghajanian GK (1978) Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra. Brain Res 150: 69–84
Hammond C, Deniau JM, Rizk A, Fegér J (1978) Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat. Brain Res 151: 235–244
Hammond C, Rouzaire-Dubois B, Fegér J, Jackson A, Crossman AR (1983a) Anatomical and electrophysiological studies on the reciprocal projections between the subthalamic nucleus and the nucleus tegmenti pedunculopontinus in the rat. Neuroscience 9: 41–55
Hammond C, Shibazaki T, Rouzaire-Dubois B (1983b) Branched output neurons of the rat subthalamic nucleus: electrophysiological study of the synaptic effects on identified cells in the two main target nuclei: the entopeduncular nucleus and substantia nigra. Neuroscience 9: 511–520
Hicks TP, Hall JG, McLennan H (1978) Ranking of excitatory ammo acids by the antagonists glutamic acid diethylester and D-α-aminoadipic acid. Can J Physiol Pharmacol 56: 901–907
Jackson A, Crossman AR (1983) Nucleus tegmenti pedunculopontinus: efferent connections with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport of horseradish peroxidase. Neuroscience 10: 725–765
Joëls M, Urban IJA (1984) Electrophysiological and pharmacological evidence in favor of amino acid neurotransmission in fimbria-fornix fibers innervating the lateral septal complex of rats. Exp Brain Res 54: 455–462
Kimura H, McGeer PL, Peng JH, McGeer EG (1981) The central cholinergic system studied by choline acetyltransferase immunohistochemistry in the cat. J Comp Neurol 200: 151–201
Krnjević K, Phillis JW (1963) Pharmacological properties of acetylcholine-sensitive cells in the cerebral cortex. J Physiol (Lond) 166: 328–350
Llinás R, Greenfield SA, Jahnsen H (1984) Electrophysiology of pars compacta cells in the in vitro substantia nigra — a possible mechanism for dendritic release. Brain Res 294: 127–132
McGeer EG, McGeer PL (1984) Substantia nigra cell death from kainic acid or folic acid injections into the pontine tegmentum. Brain Res 298: 339–342
McLennan H, Hicks TP (1978) Pharmacological characterization of the excitatory cholinergic receptors of rat central neurones. Neuropharmacology 17: 329–334
McLennan H, Hicks TP, Hall JG (1981) Receptors for the excitatory amino acids. In: DeFeudis FV, Mandel P (eds) Amino acid neurotransmitters. Raven Press, New York, pp 213–220
McNair JL, Sutin J, Tsubokawa T (1972) Suppression of cell firing in the substantia nigra by caudate nucleus stimulation. Exp Neurol 37: 395–411
Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1984) Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry. Neuroscience 12: 669–686
Moon-Edley S, Graybiel AM (1983) The afferent and efferent connections of the feline nucleus tegmenti pedunculopontinus pars compacta. J Comp Neurol 217: 187–215
Nieoullon A, Dusticier N (1983) Glutamate uptake, glutamate decarboxylase and choline acetyltransferase in subcortical areas after sensorimotor cortical ablations in the cat. Brain Res Bull 10: 287–293
Ricciardi G, Forchetti C, Gasbarri A, Scarnati E, Pacitti C (1981) Neuroexcitatory properties of kainic acid. II. Neuronal damages following intracerebral microinjections in behavioural rats. Boll Soc Ital Biol Sper 57: 919–925
Saper CB, Loewy AD (1982) Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry. Brain Res 252: 367–372
Satoh K, Armstrong DM, Fibiger HC (1983) A comparison of the distribution of central cholinergic neurons as demonstrated by acetylcholinesterase pharmacohistochemistry and choline acetyltransferase immunohistochemistry. Brain Res Bull 11: 693–720
Scarnati E, Pacitti C (1982) Neuronal responses to iontophoretically applied dopamine, glutamate and GABA of identified dopaminergic cells in the rat substantia nigra after kainic acidinduced destruction of the striatum. Exp Brain Res 46: 377–382
Scarnati E, Campana E, Pacitti C (1983) The functional role of the nucleus accumbens in the control of the substantia nigra: electrophysiological investigations in intact and striatumglobus pallidus lesioned rats. Brain Res 265: 249–257
Scarnati E, Campana E, Pacitti C (1984) Pedunculopontineevoked excitation of substantia nigra neurons in the rat. Brain Res 304: 351–361
Schultz W, Ruffieux A, Aebischer P (1983) The activity of pars compacta neurons of the monkey substantia nigra in relation to motor activation. Exp Brain Res 51: 377–387
Spencer HJ (1976) Antagonism of cortical excitation of striatal neurons by glutamic acid diethylester: evidence for glutamic acid as an excitatory transmitter in the rat striatum. Brain Res 102: 91–101
Sugimoto T, Hattori T (1984) Organization and efferent projections of nucleus tegmenti pedunculopontinus pars compacta with special reference to its cholinergic aspects. Neuroscience 11: 931–946
Thomson AM, West BC, Lodge D (1985) An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine? Nature 313: 479–481
Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand Suppl 367: 1–48
Waszczak BL, Walters JR (1983) Dopamine modulation of the effects of γ-aminobutyric acid on substantia nigra pars reticulata neurons. Science 220: 218–221
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Scarnati, E., Proia, A., Campana, E. et al. A microiontophoretic study on the nature of the putative synaptic neurotransmitter involved in the pedunculopontine-substantia nigra pars compacta excitatory pathway of the rat. Exp Brain Res 62, 470–478 (1986). https://doi.org/10.1007/BF00236025
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DOI: https://doi.org/10.1007/BF00236025