title: Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees.
abstract: Pesticides that target cholinergic neurotransmission are highly effective, but their use has been implicated in insect pollinator population decline. Honeybees are exposed to two widely used classes of cholinergic pesticide: neonicotinoids (nicotinic receptor agonists) and organophosphate miticides (acetylcholinesterase inhibitors). Although sublethal levels of neonicotinoids are known to disrupt honeybee learning and behaviour, the neurophysiological basis of these effects has not been shown. Here, using recordings from mushroom body Kenyon cells in acutely isolated honeybee brain, we show that the neonicotinoids imidacloprid and clothianidin, and the organophosphate miticide coumaphos oxon, cause a depolarization-block of neuronal firing and inhibit nicotinic responses. These effects are observed at concentrations that are encountered by foraging honeybees and within the hive, and are additive with combined application. Our findings demonstrate a neuronal mechanism that may account for the cognitive impairments caused by neonicotinoids, and predict that exposure to multiple pesticides that target cholinergic signalling will cause enhanced toxicity to pollinators.
authors.affiliation: Division of Neuroscience, Medical Research Institute, Ninewells Medical School, University of Dundee, Dundee, UK.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Palmer
authors.forename: Christopher
authors.initials: C
authors.lastname: Moffat
authors.forename: Nastja
authors.initials: N
authors.lastname: Saranzewa
authors.forename: Jenni
authors.initials: J
authors.lastname: Harvey
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: Wright
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Connolly
mesh_terms: D000818:Animals; D001516:Bees; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003372:Coumaphos / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D024521:Mushroom Bodies / Q000166:cytology / Q000187:drug effects*; D000073943:Neonicotinoids; D009474:Neurons / Q000187:drug effects*; D009574:Nitro Compounds / Q000494:pharmacology; D010575:Pesticides / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D007093:Imidazoles; D000073943:Neonicotinoids; D009574:Nitro Compounds; D010575:Pesticides; C082359:imidacloprid; D003372:Coumaphos
references.citation: Pest Manag Sci. 2003 Mar;59(3):269-78
references.pmid: 12639043
references.citation: J Econ Entomol. 2009 Apr;102(2):474-9
references.pmid: 19449624
references.citation: Science. 2012 Apr 20;336(6079):351-2
references.pmid: 22461500
references.citation: Anal Biochem. 2000 Oct 1;285(1):76-81
references.pmid: 10998265
references.citation: J Physiol. 1999 Feb 1;514 ( Pt 3):759-68
references.pmid: 9882748
references.citation: J Mol Neurosci. 2001 Aug;17(1):1-12
references.pmid: 11665858
references.citation: Curr Opin Neurobiol. 2000 Dec;10(6):790-5
references.pmid: 11240291
references.citation: Environ Entomol. 2007 Oct;36(5):1238-45
references.pmid: 18284749
references.citation: Annu Rev Pharmacol Toxicol. 2005;45:247-68
references.pmid: 15822177
references.citation: Nat Rev Neurosci. 2003 Apr;4(4):266-75
references.pmid: 12671643
references.citation: Pest Manag Sci. 2001 Jul;57(7):577-86
references.pmid: 11464788
references.citation: PLoS One. 2011 Feb 23;6(2):e14720
references.pmid: 21373182
references.citation: Aust J Biol Sci. 1966 Aug;19(4):619-33
references.pmid: 5970060
references.citation: J Neurochem. 2006 Oct;99(2):608-15
references.pmid: 16899070
references.citation: Ecotoxicol Environ Saf. 2004 Mar;57(3):410-9
references.pmid: 15041263
references.citation: J Neurophysiol. 2010 May;103(5):2770-82
references.pmid: 20237312
references.citation: Pest Manag Sci. 2008 Nov;64(11):1099-105
references.pmid: 18561166
references.citation: PLoS One. 2011;6(11):e26796
references.pmid: 22073195
references.citation: Ecotoxicology. 2004 Aug;13(6):589-601
references.pmid: 15526863
references.citation: J Neurosci. 1994 Aug;14(8):4600-12
references.pmid: 7519255
references.citation: Ecotoxicology. 2011 Jan;20(1):149-57
references.pmid: 21080222
references.citation: J Insect Physiol. 2010 Sep;56(9):1341-8
references.pmid: 20438731
references.citation: Nature. 2012 Nov 1;491(7422):105-8
references.pmid: 23086150
references.citation: J Neurophysiol. 2009 Nov;102(5):2834-45
references.pmid: 19759323
references.citation: J Exp Biol. 2003 Jan;206(Pt 1):117-29
references.pmid: 12456702
references.citation: Invert Neurosci. 2007 Mar;7(1):53-66
references.pmid: 17216290
references.citation: PLoS One. 2008;3(12):e4071
references.pmid: 19115015
references.citation: J Neurophysiol. 2009 Sep;102(3):1538-50
references.pmid: 19553491
references.citation: J Insect Physiol. 2004 Oct;50(10):867-79
references.pmid: 15518655
references.citation: Trends Ecol Evol. 2010 Jun;25(6):345-53
references.pmid: 20188434
references.citation: J Neurophysiol. 1999 Apr;81(4):1749-59
references.pmid: 10200210
references.citation: Pest Manag Sci. 2004 Nov;60(11):1056-62
references.pmid: 15532678
references.citation: Anal Chem. 2003 May 1;75(9):2027-33
references.pmid: 12720336
references.citation: Ecotoxicology. 2012 May;21(4):973-92
references.pmid: 22350105
references.citation: J Neurophysiol. 2004 Oct;92(4):2589-603
references.pmid: 15190098
references.citation: PLoS One. 2012;7(1):e30023
references.pmid: 22253863
references.citation: PLoS One. 2012;7(1):e29268
references.pmid: 22235278
references.citation: J Neurophysiol. 2011 Oct;106(4):1604-13
references.pmid: 21734106
references.citation: J Neurophysiol. 1999 Aug;82(2):1091-6
references.pmid: 10444704
references.citation: Toxicol Sci. 2004 Dec;82(2):545-54
references.pmid: 15342957
references.citation: Environ Sci Technol. 2006 Apr 1;40(7):2448-54
references.pmid: 16646488
references.citation: J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2004 Oct;190(10):807-21
references.pmid: 15309481
references.citation: Science. 2012 Apr 20;336(6079):348-50
references.pmid: 22461498
references.citation: Ecotoxicology. 2010 Nov;19(8):1612-9
references.pmid: 20872243
references.citation: Neurosci Lett. 2002 Mar 15;321(1-2):13-6
references.pmid: 11872245
references.citation: Neurotoxicology. 2007 Jul;28(4):829-42
references.pmid: 17561262
references.citation: J Agric Food Chem. 2003 Dec 31;51(27):8005-10
references.pmid: 14690387
references.citation: PLoS One. 2010 Mar 19;5(3):e9754
references.pmid: 20333298