• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Sep 1985; 82(18): 6344–6348.
PMCID: PMC391050

Two types of muscarinic response to acetylcholine in mammalian cortical neurons.

Abstract

Applications of acetylcholine (AcCho) to pyramidal cells of guinea pig cingulate cortical slices maintained in vitro result in a short latency inhibition, followed by a prolonged increase in excitability. Cholinergic inhibition is mediated through the rapid excitation of interneurons that utilize the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This rapid excitation of interneurons is associated with a membrane depolarization and a decrease in neuronal input resistance. In contrast, AcCho-induced excitation of pyramidal cells is due to a direct action that produces a voltage-dependent increase in input resistance. In the experiments reported here, we investigated the possibility that these two responses are mediated by different subclasses of cholinergic receptors. The inhibitory and slow excitatory responses of pyramidal neurons were blocked by muscarinic but not by nicotinic antagonists. Pirenzepine was more effective in blocking the AcCho-induced slow depolarization than in blocking the hyperpolarization of pyramidal neurons. The two responses also varied in their sensitivity to various cholinergic agonists, making it possible to selectively activate either. These data suggest that AcCho may produce two physiologically and pharmacologically distinct muscarinic responses on neocortical neurons: slowly developing voltage-dependent depolarizations associated with an increase in input resistance in pyramidal cells and short-latency depolarizations associated with a decrease in input resistance in presumed GABAergic interneurons.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Houser CR, Crawford GD, Barber RP, Salvaterra PM, Vaughn JE. Organization and morphological characteristics of cholinergic neurons: an immunocytochemical study with a monoclonal antibody to choline acetyltransferase. Brain Res. 1983 Apr 25;266(1):97–119. [PubMed]
  • Mesulam MM, Mufson EJ, Wainer BH, Levey AI. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience. 1983 Dec;10(4):1185–1201. [PubMed]
  • Houser CR, Crawford GD, Salvaterra PM, Vaughn JE. Immunocytochemical localization of choline acetyltransferase in rat cerebral cortex: a study of cholinergic neurons and synapses. J Comp Neurol. 1985 Apr 1;234(1):17–34. [PubMed]
  • Wainer BH, Bolam JP, Freund TF, Henderson Z, Totterdell S, Smith AD. Cholinergic synapses in the rat brain: a correlated light and electron microscopic immunohistochemical study employing a monoclonal antibody against choline acetyltransferase. Brain Res. 1984 Aug 6;308(1):69–76. [PubMed]
  • Benardo LS, Prince DA. Ionic mechanisms of cholinergic excitation in mammalian hippocampal pyramidal cells. Brain Res. 1982 Oct 14;249(2):333–344. [PubMed]
  • Brown DA, Adams PR. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature. 1980 Feb 14;283(5748):673–676. [PubMed]
  • Cole AE, Nicoll RA. Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science. 1983 Sep 23;221(4617):1299–1301. [PubMed]
  • Constanti A, Galvan M. M-current in voltage-clamped olfactory cortex neurones. Neurosci Lett. 1983 Aug 19;39(1):65–70. [PubMed]
  • Halliwell JV, Adams PR. Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 1982 Oct 28;250(1):71–92. [PubMed]
  • Woody CD, Swartz BE, Gruen E. Effects of acetylcholine and cyclic GMP on input resistance of cortical neurons in awake cats. Brain Res. 1978 Dec 15;158(2):373–395. [PubMed]
  • Haas HL. Cholinergic disinhibition in hippocampal slices of the rat. Brain Res. 1982 Feb 4;233(1):200–204. [PubMed]
  • Segal M. Multiple action of acetylcholine at a muscarinic receptor studied in the rat hippocampal slice. Brain Res. 1982 Aug 19;246(1):77–87. [PubMed]
  • Dodd J, Horn JP. Muscarinic inhibition of sympathetic C neurones in the bullfrog. J Physiol. 1983 Jan;334:271–291. [PMC free article] [PubMed]
  • Gallagher JP, Griffith WH, Shinnick-Gallagher P. Cholinergic transmission in cat parasympathetic ganglia. J Physiol. 1982 Nov;332:473–486. [PMC free article] [PubMed]
  • Hartzell HC, Kuffler SW, Stickgold R, Yoshikami D. Synaptic excitation and inhibition resulting from direct action of acetylcholine on two types of chemoreceptors on individual amphibian parasympathetic neurones. J Physiol. 1977 Oct;271(3):817–846. [PMC free article] [PubMed]
  • Libet B. Generation of slow inhibitory and excitatory postsynaptic potentials. Fed Proc. 1970 Nov-Dec;29(6):1945–1956. [PubMed]
  • Birdsall NJ, Burgen AS, Hulme EC. The binding of agonists to brain muscarinic receptors. Mol Pharmacol. 1978 Sep;14(5):723–736. [PubMed]
  • Hammer R, Berrie CP, Birdsall NJ, Burgen AS, Hulme EC. Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature. 1980 Jan 3;283(5742):90–92. [PubMed]
  • Williams M, Robinson JL. Binding of the nicotinic cholinergic antagonist, dihydro-beta-erythroidine, to rat brain tissue. J Neurosci. 1984 Dec;4(12):2906–2911. [PubMed]
  • Phillis JW, York DH. Pharmacological studies on a cholinergic inhibition in the cerebral cortex. Brain Res. 1968 Sep;10(3):297–306. [PubMed]
  • Ashe JH, Yarosh CA. Differential and selective antagonism of the slow-inhibitory postsynaptic potential and slow-excitatory postsynaptic potential by gallamine and pirenzepine in the superior cervical ganglion of the rabbit. Neuropharmacology. 1984 Nov;23(11):1321–1329. [PubMed]
  • Gutnick MJ, Prince DA. Dye coupling and possible electrotonic coupling in the guinea pig neocortical slice. Science. 1981 Jan 2;211(4477):67–70. [PubMed]
  • Vogt BA, Gorman AL. Responses of cortical neurons to stimulation of corpus callosum in vitro. J Neurophysiol. 1982 Dec;48(6):1257–1273. [PubMed]
  • ROSZKOWSKI AP. An unusual type of sympathetic ganglionic stimulant. J Pharmacol Exp Ther. 1961 May;132:156–170. [PubMed]
  • Birdsall NJ, Burgen AS, Hulme EC, Stockton JM, Zigmond MJ. The effect of McN-A-343 on muscarinic receptors in the cerebral cortex and heart. Br J Pharmacol. 1983 Feb;78(2):257–259. [PMC free article] [PubMed]
  • Hammer R. Subclasses of muscarinic receptors and pirenzepine. Further experimental evidence. Scand J Gastroenterol Suppl. 1982;72:59–67. [PubMed]
  • Coyle JT, Price DL, DeLong MR. Alzheimer's disease: a disorder of cortical cholinergic innervation. Science. 1983 Mar 11;219(4589):1184–1190. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...