Reference Report

Reference
Citation	Tsai, L.T., Bainton, R.J., Blau, J., Heberlein, U. (2004). Lmo Mutants Reveal a Novel Role for Circadian Pacemaker Neurons in Cocaine-Induced Behaviors. PLoS Biol. 2(12): e408. (Export to RIS)
FlyBase ID	FBrf0180477
Publication Type	Research paper
PubMed ID	15550987
PubMed Abstract	Drosophila has been developed recently as a model system to investigate the molecular and neural mechanisms underlying responses to drugs of abuse. Genetic screens for mutants with altered drug-induced behaviors thus provide an unbiased approach to define novel molecules involved in the process. We identified mutations in the Drosophila LIM-only (LMO) gene, encoding a regulator of LIM-homeodomain proteins, in a genetic screen for mutants with altered cocaine sensitivity. Reduced Lmo function increases behavioral responses to cocaine, while Lmo overexpression causes the opposite effect, reduced cocaine responsiveness. Expression of Lmo in the principal Drosophila circadian pacemaker cells, the PDF-expressing ventral lateral neurons (LN(v)s), is sufficient to confer normal cocaine sensitivity. Consistent with a role for Lmo in LN(v)function,Lmomutants also show defects in circadian rhythms of behavior. However, the role for LN(v)s in modulating cocaine responses is separable from their role as pacemaker neurons: ablation or functional silencing of the LN(v)s reduces cocaine sensitivity, while loss of the principal circadian neurotransmitter PDF has no effect. Together, these results reveal a novel role for Lmo in modulating acute cocaine sensitivity and circadian locomotor rhythmicity, and add to growing evidence that these behaviors are regulated by shared molecular mechanisms. The finding that the degree of cocaine responsiveness is controlled by the Drosophila pacemaker neurons provides a neuroanatomical basis for this overlap. We propose that Lmo controls the responsiveness of LN(v)s to cocaine, which in turn regulate the flies' behavioral sensitivity to the drug.
DOI	10.1371/journal.pbio.0020408
Related Publication(s)
Review	This Is Your Fly's Brain on Drugs. Anonymous, 2005, PLoS Biol. 2(12): e444 [FBrf0188405]
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Biol.
Title	PLoS Biology
Publication Year	2003-
ISBN/ISSN	1545-7885 1544-9173
Data from Reference
Aberrations (1)
	Df(3R)Tl-P
Alleles (25)
	Avic\GFP^Scer\UAS.cUa Bx¹ Bx² Bx³ Bx^EP1306 Bx^EP1383 Bx^EP1394 Bx^hdpR26 Bx^hdpR590 Bx^hdp-rev83 Bx^J Bx^MS1096 Bx^pdrm Bx^Scer\UAS.cZa Ctet\TeTxLC^{IMPTNT-V.Scer\UAS} Ctet\TeTxLC^TNT.Scer\UAS Ecol\lacZ^Scer\UAS.cBa EP443^EP443 Hsap\KCNJ2^{Scer\UAS.T:Avic\GFP-EGFP} Pdf⁰¹ Scer\GAL4^Bx-pdrm Scer\GAL4^hs.PB Scer\GAL4^P2.4.Pdf T:Avic\GFP^EGFP W^Scer\UAS.cZa
Constructs (9)
	P{GAL4-Hsp70.PB} P{Pdf-GAL4.P2.4} P{UAS-Bx.Z} P{UAS-GFP.U} P{UAS-Hsap\KCNJ2.EGFP} P{UAS-lacZ.B} P{UAS-TeTxLC.(-)V} P{UAS-TeTxLC.tnt} P{UAS-W.Z}
Genes (9)
	Avic\GFP Bx Ctet\TeTxLC Ecol\lacZ EP443 Hsap\KCNJ2 Pdf Scer\GAL4 W
Insertions (9)
	3S18{}Bx^J P{EP}Bx^EP1306 P{EP}Bx^EP1383 P{EP}Bx^EP1394 P{EP}EP443^EP443 P{GawB}Bx^MS1096 P{GawB}Bx^pdrm P{UAS-Bx.Z}1 P{UAS-Bx.Z}2