Innate behaviors have their origins in the specification of neural fates during development. Within Drosophila, BTB (Bric-a-brac,Tramtrack, Broad) domain proteins such as Fruitless are known to play key roles in the neural differentiation underlying such responses. We previously identified a gene, which we have termed jim lovell (lov), encoding a BTB protein with a role in gravity responses. To understand more fully the behavioral roles of this gene we have investigated its function through several approaches. Transcript and protein expression patterns have been examined and behavioral phenotypes of new lov mutations have been characterized. Lov is a nuclear protein, suggesting a role as a transcriptional regulator, as for other BTB proteins. In late embryogenesis, Lov is expressed in many CNS and PNS neurons. An examination of the PNS expression indicates that lov functions in the late specification of several classes of sensory neurons. In particular, only two of the five abdominal lateral chordotonal neurons express Lov, predicting functional variation within this highly similar group. Surprisingly, Lov is also expressed very early in embryogenesis in ways that suggests roles in morphogenetic movements, amnioserosa function and head neurogenesis. The phenotypes of two new lov mutations that delete adjacent non-coding DNA regions are strikingly different suggesting removal of different regulatory elements. In lov(47) , Lov expression is lost in many embryonic neurons including the two lateral chordotonal neurons. lov(47) mutant larvae show feeding and locomotor defects including spontaneous backward movement. Adult lov(47) males perform aberrant courtship behavior distinguished by courtship displays that are not directed at the female. lov(47) adults also show more defective negative gravitaxis than the previously isolated lov(91Y) mutant. In contrast, lov(66) produces largely normal behavior but severe female sterility associated with ectopic lov expression in the ovary. We propose a negative regulatory role for the DNA deleted in lov(66) .
To thrive in any given environment, mobile creatures must be able to learn from the outcomes of both successful and disappointing events. To learn from success, the brain relies on signals originating in the ventral tegmental area and substantia nigra that result in increased release of dopamine in the striatum. Recently, it was shown that to learn from disappointment the brain relies on signals originating in the lateral habenula, which indirectly inhibit dopaminergic activity. The habenula is a small brain region that has been shown in mice to be critical for the appearance of nicotine withdrawal symptoms. The nicotinic acetylcholine receptor subunits expressed in the medial habenula are necessary to observe withdrawal symptoms in mice, and blocking nicotinic activity in the medial habenula only is sufficient to precipitate withdrawal in dependent mice. In addition, recent genome wide association studies have shown that in humans, genetic variants in the same nicotinic receptor subunits are at least partially responsible for the genetic predisposition to become a smoker. The habenula is linked not only to nicotine, but also to the effects of several other drugs. We postulate that the continuous use of drugs of abuse results in habenular hyperactivity as a compensatory mechanism for artificially elevated dopamine release. Drug withdrawal would then result in non-compensated habenular hyperactivity, and could be thought of as a state of continuous disappointment (or a negative emotional state), driving repeated drug use. We believe that drugs that alter habenular activity may be effective therapies against tobacco smoke and drug addiction in general.
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