title: Reciprocal regulation of inhibitory synaptic transmission by nicotinic and muscarinic receptors in rat nucleus accumbens shell.
abstract: Medium spiny neurones (MSNs) in the nucleus accumbens (NAc) are the principal neurones whose activities are regulated by GABAergic inputs from MSNs and fast-spiking interneurones (FSNs). Cholinergic interneurones play important roles in the regulation of activity in MSNs; however, how acetylcholine modulates inhibitory synaptic transmission from MSNs/FSNs to MSNs remains unknown. We performed paired whole-cell patch-clamp recordings from MSNs and FSNs in rat NAc shell slice preparations and examined cholinergic effects on unitary inhibitory postsynaptic currents (uIPSCs). Carbachol (1 μM) suppressed uIPSC amplitude by 58.3 ± 8.0% in MSN→MSN connections, accompanied by increases in paired-pulse ratio and failure rate, suggesting that acetylcholine reduces the probability of GABA release from the synaptic terminals of MSNs. Carbachol-induced uIPSC suppression was antagonised by 100 μM atropine, and was mimicked by pilocarpine (1 μM) and acetylcholine (1 μM) but not nicotine (1 μM). Application of AM251 slightly reduced carbachol-induced uIPSC suppression (30.8 ± 8.9%), suggesting an involvement of endocannabinoid signalling in muscarinic suppression of uIPSCs. In contrast, FSN→MSN connections showed that pilocarpine had little effect on the uIPSC amplitude, whereas both nicotine and acetylcholine facilitated uIPSC amplitude, with decreases in failure rate and paired-pulse ratio, suggesting that nicotine-induced uIPSC facilitation is mediated by presynaptic mechanisms. Miniature IPSC recordings support these hypotheses of presynaptic cholinergic mechanisms. These results suggest a differential role for muscarinic and nicotinic receptors in GABA release, which depends on presynaptic neuronal subtypes in the NAc shell.
authors.affiliation: M. Kobayashi: Department of Pharmacology, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan. kobayashi.masayuki@nihon-u.ac.jp.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Katsuko
authors.initials: K
authors.lastname: Ebihara
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koshikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism / Q000502:physiology; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D010862:Pilocarpine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D001285:Atropine; D002217:Carbachol; D000109:Acetylcholine
references.citation: J Neurophysiol. 2004 Mar;91(3):1111-21
references.pmid: 14573550
references.citation: Front Syst Neurosci. 2011 Mar 03;5:11
references.pmid: 21427783
references.citation: Neuroscientist. 2003 Feb;9(1):23-36
references.pmid: 12580337
references.citation: Trends Neurosci. 2000 Mar;23(3):120-6
references.pmid: 10675916
references.citation: J Neurosci. 2007 Apr 4;27(14):3663-76
references.pmid: 17409230
references.citation: Neurosci Lett. 1992 Apr 13;138(1):137-40
references.pmid: 1407652
references.citation: J Neurosci. 2008 May 21;28(21):5504-12
references.pmid: 18495884
references.citation: J Physiol. 2000 Mar 1;523 Pt 2:425-39
references.pmid: 10699086
references.citation: Neuroscience. 2010 May 19;167(3):864-71
references.pmid: 20219639
references.citation: J Neurosci. 1993 Nov;13(11):4908-23
references.pmid: 7693897
references.citation: Nat Neurosci. 1999 Jun;2(6):499-500
references.pmid: 10448211
references.citation: Eur J Neurosci. 2002 Dec;16(12):2279-90
references.pmid: 12492422
references.citation: J Comp Neurol. 1985 Aug 15;238(3):286-307
references.pmid: 4044917
references.citation: Eur J Neurosci. 2003 Feb;17(3):613-22
references.pmid: 12581179
references.citation: J Comp Neurol. 2004 Feb 9;469(3):325-39
references.pmid: 14730585
references.citation: J Neurophysiol. 2005 May;93(5):2507-19
references.pmid: 15615835
references.citation: J Neurophysiol. 2006 Oct;96(4):2034-41
references.pmid: 16837663
references.citation: Prog Neurobiol. 1994 Apr;42(6):719-61
references.pmid: 7938546
references.citation: Neuron. 1995 Apr;14(4):795-802
references.pmid: 7718241
references.citation: Trends Neurosci. 1995 Dec;18(12):527-35
references.pmid: 8638293
references.citation: Neuroscience. 2013 Apr 16;236:332-44
references.pmid: 23380504
references.citation: J Neurophysiol. 2012 Mar;107(5):1431-42
references.pmid: 22190629
references.citation: J Neurosci. 2003 Oct 22;23(29):9664-74
references.pmid: 14573546
references.citation: Cereb Cortex. 2008 Feb;18(2):315-30
references.pmid: 17517679
references.citation: Nat Neurosci. 2011 Dec 11;15(1):123-30
references.pmid: 22158514
references.citation: Neuroscience. 1996 Aug;73(3):751-60
references.pmid: 8809795
references.citation: Neuroscience. 1994 Jan;58(2):389-97
references.pmid: 8152545
references.citation: Science. 2010 Dec 17;330(6011):1677-81
references.pmid: 21164015
references.citation: J Neurosci. 2007 Jan 17;27(3):496-506
references.pmid: 17234582
references.citation: Synapse. 2005 Jan;55(1):17-25
references.pmid: 15499607
references.citation: J Neurosci. 1990 Feb;10(2):508-19
references.pmid: 2303856
references.citation: Neuropharmacology. 1999 Sep;38(9):1397-407
references.pmid: 10471094
references.citation: J Neurosci. 1991 Sep;11(9):2838-47
references.pmid: 1679123
references.citation: J Neurophysiol. 2012 Jan;107(2):692-703
references.pmid: 22049335
references.citation: J Neurosci. 1999 Aug 1;19(15):6427-38
references.pmid: 10414971
references.citation: J Neurophysiol. 2005 Mar;93(3):1816-9
references.pmid: 15456801
references.citation: Brain Res. 2007 Jun 4;1152:49-56
references.pmid: 17459351