Summary
Several lines of evidence suggest a role for ACh in the mediation of cerebello-thalamic transmission. The physiological, pharmacological and biochemical experiments described were designed to test this hypothesis for the rat cerebello-thalamic pathway. Unilateral electrolytic lesions of the superior cerebellar peduncle resulted in modest falls of CAT from both ventromedial thalamic nuclei (contralateral 35%, ipsilateral 15%). Iontophoretic application of ACh to relay cells evokes three types of response (i) excitation (ii) inhibition (iii) polyphasic combinations of (i) and (ii). The type of response evoked was directly related to the firing pattern of the cell. Thus, for example, excitatory responses were never recorded during high-frequency bursting but were easily evoked following a switch to tonic, single-spike activity. All responses to ACh and synaptic responses to cerebellar stimulation were sensitive to muscarinic but not to nicotinic cholinergic antagonists. The nicotinic antagonist mecamylamine was a potent blocker of excitant amino acid responses but had no effect on cerebellarevoked synaptic responses. Cholinergic and anticholinergic agents had a profound action on relay cell firing pattern. ACh promoted single-spike activity whereas atropine promoted high-frequency bursting. The actions of ACh are discussed with reference to recently discovered voltage-sensitive ionic conductances. Because of the modulatory action of ACh on relay cell firing pattern and excitability no firm conclusion can be reached concerning the hypothesis under test here. We tentatively suggest a dual role for ACh as both neurotransmitter and neuromodulator.
Similar content being viewed by others
References
Adams PR, Brown DA (1980) Luteinizing hormone-releasing factor and muscarinic agonists act on the same voltagesensitive K+ current in bullfrog sympathetic neurones. Br J Pharmacol 68: 353–355
Adams PR, Brown DA, Halliwell JV (1981) Cholinergic regulation of M-current in hippocampal pyramidal cells. J Physiol (Lond) 317: 29–30
Angel A, Dodd J, Gray JD (1976) Fluctuating anaesthetic state in the rat anaesthetized with urethane. J Physiol (Lond) 259: 11P
Ben-Ari Y, Dingledine R, Kanazawa I, Kelly JS (1976) Inhibitory effects of acetylcholine on neurones in the feline nucleus reticularis thalami. J Physiol (Lond) 261: 647–671
Brown DA, Adams PR (1980) Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature 283: 673–676
Curtis DR (1966) Pharmacological studies of thalamic neurones. In: Purpura DP, Yahr MD (eds) The Thalamus. Columbia University Press, New York, pp 186–191
Davis R (1966) Acetylcholine sensitive neurones in the ventrolateral thalamic nucleus. In: Purpura DP, Yahr MD (eds) The Thalamus. Columbia University Press, New York, pp 193–195
Déschênes M, Roy JP, Steriade M (1982) Thalamic bursting mechanism: an inward slow current revealed by membrane hyperpolarization. Brain Res 239: 289–293
Dingledine R, Kelly JS (1977) Brain-stem stimulation and acetylcholine-evoked inhibition of neurones in the feline nucleus reticularis thalami. J Physiol (Lond) 271: 135–154
Duggan AW, Hall JG (1975) Inhibition of thalamic neurones by acetylcholine. Brain Res 100: 445–445
Fonnum F (1975) A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem 24: 407–409
Frigyesi TL, Purpura DP (1966) Acetylcholine sensitivity of thalamic synaptic organizations activated by brachium conjunctivum stimulation. Arch Int Pharmacodyn 163: 110–131
Halliwell JV, Adams PR (1982) Voltage clamp analysis of muscarinic excitation in hippocampal neurones. Brain Res 250: 71–92
Herkenham M (1980) Laminar organization of thalamic projections to rat neocortex. Science 207: 532–534
James TA, MacLeod NK (1981) Regulation of muscarinic responses of ventromedial thalamic neurones. J Physiol (Lond) 315: 32P
James TA, MacLeod NK, Starr MS (1981) The cerebellothalamic pathway in the rat. J Physiol (Lond) 313: 29–30P
Krnjević K (1981) Acetylcholine as a modulator of amino-acid mediated synaptic transmission. In: Lombardini JB, Kenny AD (eds) The role of peptides and amino acids as neurotransmitters. Hayden, NY
Krnjević K, Pumain R, Renaud L (1971) The mechanism of excitation by acetyl-choline in the cerebral cortex. J Physiol (Lond) 215: 247–268
Llinás R, Jahnsen H (1982) Electrophysiology of mammalian thalamic neurones in vitro. Nature 297: 406–408
Llinás R, Yarom Y (1981a) Electrophysiology of inferior olivary neurones in vitro. Different types of voltage-dependent ionic conductance. J Physiol (Lond) 315: 549–567
Llinás R, Yarom Y (1981b) Properties and distribution of ionic conductances generating electroresponsiveness of inferior olivary neurones in vitro. J Physiol (Lond) 315: 569–584
MacLeod NK, James TA (1984) Regulation of cerebello-cortical transmission in the rat ventromedial thalamic nucleus. Exp Brain Res 55: 535–552
MacLeod NK, James TA, Kilpatrick IC, Starr MS (1980) Evidence for a GABAergic nigrothalamic pathway in the rat. II. Electrophysiological studies. Exp Brain Res 40: 55–61
Marshall KC, Flumerfelt BA, Gwyn DG (1980) Acetylcholinesterase activity and acetylcholine effects in the cerebello-rubrothalamic pathway of the cat. Brain Res 180: 493–504
Marshall KC, McLennan H (1972) The synaptic activation of neurones in the feline ventrolateral thalamic nucleus: possible cholinergic mechanisms. Exp Brain Res 15: 472–483
Marshall KC, Murray SJ (1980) Cholinergic facilitation of thalamic relay transmission in the cat. Exp Neurol 69: 318–333
McCance I, Phillis J, Westerman RA (1968) Acetylcholine sensitivity of thalamic neurones: its relation to synaptic transmission. Br J Pharmac Chemother 21: 635–651
McLennan H, Huffman RD, Marshall KC (1968) Patterns of excitation of thalamic neurones by aminoacids and by acetylcholine. Nature 219: 387–388
Mesulam M-M, Mufson EJ, Wainer BH, Levey AI (1983) Central cholinergic pathways in the rat. Neuroscience 10: 1185–1201
Montplaisir JY (1975) Cholinergic mechanisms in cortical activation during arousal. Electroencephalogr Clin Neurophysiol 38: 263–272
Phillis JW (1968) Acetylcholinesterase in the feline cerebellum. J Neurochem 15: 691–698
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
MacLeod, N.K., James, T.A. & Starr, M.S. Muscarinic action of acetylcholine in the rat ventromedial thalamic nucleus. Exp Brain Res 55, 553–561 (1984). https://doi.org/10.1007/BF00235286
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00235286