Young-Cho Kim

University of Texas at El Paso, El Paso, TX, United States

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Publications (10)69.11 Total impact

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    ABSTRACT: Associative learning is a fundamental form of behavioral plasticity. Octopamine plays central roles in various learning types in invertebrates; however, the target receptors and underlying mechanisms are poorly understood. Drosophila provides a powerful system to uncover the mechanisms for learning and memory. Here, we report that OAMB in the mushroom body neurons mediates the octopamine's signal for appetitive olfactory learning. The octopamine receptor OAMB has two isoforms (OAMB-K3 and OAMB-AS), differing in the third cytoplasmic loop and downstream sequence. The activation of each OAMB isoform increases intracellular Ca(2+) similar to the alpha1 adrenergic receptor, while OAMB-K3 additionally stimulates cAMP production. The oamb-null mutants showed severely impaired learning in appetitive olfactory conditioning that tests flies' capacity to learn and remember the odor associated with sugar reward. This deficit was also seen in the hypomorphic mutant with reduced OAMB expression in the mushroom bodies, the brain structure crucial for olfactory conditioning. Consistently, the oamb mutant's learning phenotype was fully rescued by conditional expression of either OAMB isoform in the mushroom body αβ and γ neurons. These results indicate that the OAMB receptor is a key molecule mediating the octopamine's signal for appetitive olfactory learning and its functional site is the mushroom body αβ and γ neurons. This study represents a critical step forward in understanding the cellular mechanism and neural circuit mediating reward learning and memory.
    Journal of Neuroscience 01/2013; 33(4):1672-7. · 6.91 Impact Factor
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    Kyung-An Han, Young-Cho Kim
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    ABSTRACT: Male fruit flies touch females during courtship. A new study finds that pheromone input received through the male's foreleg allows him to generate the courtship song appealing to female flies. This activity involves sexually dimorphic fruitless-expressing neurons in the brain.
    Current biology: CB 01/2010; 20(1):R25-8. · 10.99 Impact Factor
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    ABSTRACT: Arousal is fundamental to many behaviors, but whether it is unitary or whether there are different types of behavior-specific arousal has not been clear. In Drosophila, dopamine promotes sleep-wake arousal. However, there is conflicting evidence regarding its influence on environmentally stimulated arousal. Here we show that loss-of-function mutations in the D1 dopamine receptor DopR enhance repetitive startle-induced arousal while decreasing sleep-wake arousal (i.e., increasing sleep). These two types of arousal are also inversely influenced by cocaine, whose effects in each case are opposite to, and abrogated by, the DopR mutation. Selective restoration of DopR function in the central complex rescues the enhanced stimulated arousal but not the increased sleep phenotype of DopR mutants. These data provide evidence for at least two different forms of arousal, which are independently regulated by dopamine in opposite directions, via distinct neural circuits.
    Neuron 11/2009; 64(4):522-36. · 15.77 Impact Factor
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    ABSTRACT: Carbon-fiber microelectrodes coupled with electrochemical detection have been used extensively for the analysis of biogenic amines. In order to determine the functional role of these amines, in vivo studies have primarily used rats and mice as model organisms. Here, we report on the development of these microanalytical techniques for in vivo electrochemical detection of dopamine in the adult Drosophila melanogaster central nervous system (CNS). A triple-barrel micropipet injector was used to exogenously apply three different concentrations of dopamine, and a cylindrical carbon-fiber microelectrode was placed in the protocerebral anterior medial brain area where dopamine neurons are densely populated. Background-subtracted fast-scan cyclic voltammetry was used to measure dopamine concentration in the fly CNS. Distinct differences are shown for the clearance of exogenously applied dopamine in the brains of wild type flies versus fumin (fmn) mutants lacking a functional dopamine transporter. The current response due to oxidation of dopamine increased significantly from baseline for wild type flies following cocaine incubation. Interestingly, the current remained unchanged for mutant flies under the same conditions. These data confirm the accepted theory that cocaine blocks dopamine transporter function and validates the use of in vivo electrochemical methods to monitor dopamine uptake in Drosophila. Furthermore, after incubation with tetrodotoxin (TTX), a sodium channel blocker, there was a significant increase in peak oxidation current in the wild type flies; however, the current did not significantly change in the fmn mutant. These data suggest that factors that affect neuronal activity via ion channels such as TTX also influence the function of the dopamine transporter in Drosophila.
    Analytical Chemistry 03/2009; 81(5):1848-54. · 5.82 Impact Factor
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    ABSTRACT: The arousing and motor-activating effects of psychostimulants are mediated by multiple systems. In Drosophila, dopaminergic transmission is involved in mediating the arousing effects of methamphetamine, although the neuronal mechanisms of caffeine (CAFF)-induced wakefulness remain unexplored. Here, we show that in Drosophila, as in mammals, the wake-promoting effect of CAFF involves both the adenosinergic and dopaminergic systems. By measuring behavioral responses in mutant and transgenic flies exposed to different drug-feeding regimens, we show that CAFF-induced wakefulness requires the Drosophila D1 dopamine receptor (dDA1) in the mushroom bodies. In WT flies, CAFF exposure leads to downregulation of dDA1 expression, whereas the transgenic overexpression of dDA1 leads to CAFF resistance. The wake-promoting effects of methamphetamine require a functional dopamine transporter as well as the dDA1, and they engage brain areas in addition to the mushroom bodies.
    Proceedings of the National Academy of Sciences 12/2008; 105(51):20392-7. · 9.81 Impact Factor
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    ABSTRACT: Alcohol has a strong causal relationship with sexual arousal and disinhibited sexual behavior in humans; however, the physiological support for this notion is largely lacking and thus a suitable animal model to address this issue is instrumental. We investigated the effect of ethanol on sexual behavior in Drosophila. Wild-type males typically court females but not males; however, upon daily administration of ethanol, they exhibited active intermale courtship, which represents a novel type of behavioral disinhibition. The ethanol-treated males also developed behavioral sensitization, a form of plasticity associated with addiction, since their intermale courtship activity was progressively increased with additional ethanol experience. We identified three components crucial for the ethanol-induced courtship disinhibition: the transcription factor regulating male sex behavior Fruitless, the ABC guanine/tryptophan transporter White and the neuromodulator dopamine. fruitless mutant males normally display conspicuous intermale courtship; however, their courtship activity was not enhanced under ethanol. Likewise, white males showed negligible ethanol-induced intermale courtship, which was not only reinstated but also augmented by transgenic White expression. Moreover, inhibition of dopamine neurotransmission during ethanol exposure dramatically decreased ethanol-induced intermale courtship. Chronic ethanol exposure also affected a male's sexual behavior toward females: it enhanced sexual arousal but reduced sexual performance. These findings provide novel insights into the physiological effects of ethanol on sexual behavior and behavioral plasticity.
    PLoS ONE 02/2008; 3(1):e1391. · 3.53 Impact Factor
  • Young-Cho Kim, Hyun-Gwan Lee, Kyung-An Han
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    ABSTRACT: Drosophila has robust behavioral plasticity to avoid or prefer the odor that predicts punishment or food reward, respectively. Both types of plasticity are mediated by the mushroom body (MB) neurons in the brain, in which various signaling molecules play crucial roles. However, important yet unresolved molecules are the receptors that initiate aversive or appetitive learning cascades in the MB. We have shown previously that D1 dopamine receptor dDA1 is highly enriched in the MB neuropil. Here, we demonstrate that dDA1 is a key receptor that mediates both aversive and appetitive learning in pavlovian olfactory conditioning. We identified two mutants, dumb1 and dumb2, with abnormal dDA1 expression. When trained with the same conditioned stimuli, both dumb alleles showed negligible learning in electric shock-mediated conditioning while they exhibited moderately impaired learning in sugar-mediated conditioning. These phenotypes were not attributable to anomalous sensory modalities of dumb mutants because their olfactory acuity, shock reactivity, and sugar preference were comparable to those of control lines. Remarkably, the dumb mutant's impaired performance in both paradigms was fully rescued by reinstating dDA1 expression in the same subset of MB neurons, indicating the critical roles of the MB dDA1 in aversive as well as appetitive learning. Previous studies using dopamine receptor antagonists implicate the involvement of D1/D5 receptors in various pavlovian conditioning tasks in mammals; however, these have not been supported by the studies of D1- or D5-deficient animals. The findings described here unambiguously clarify the critical roles of D1 dopamine receptor in aversive and appetitive pavlovian conditioning.
    Journal of Neuroscience 08/2007; 27(29):7640-7. · 6.91 Impact Factor
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    ABSTRACT: Here we describe a novel set of peptidergic neurons conserved throughout all developmental stages in the Drosophila central nervous system (CNS). We show that a small complement of 28 apterous-expressing cells (Ap-let neurons) in the ventral nerve cord (VNC) of Drosophila larvae co-express numerous gene products. The products include the neuroendocrine-specific bHLH regulator called Dimmed (Dimm), four neuropeptide biosynthetic enzymes (PC2, Fur1, PAL2, and PHM), and a specific dopamine receptor subtype (dDA1). For the PC2, Fur1, and PAL2 enzymes, and for the dDA1 receptor, this neuronal pattern represents the vast majority of their total expression in the VNC. In addition, while Dimm and PHM are present in the peritracheal Inka cells in larvae, pupae, and adults, Ap, PC2, Fur1, PAL2, and dDA1 are not. PC2, PAL2, and DA1 receptor expression were all controlled by both dimm and ap. Previous genetic analysis of animals deficient in PC2 revealed an abnormal larval ecdysis phenotype. Together, these data support the hypothesis that the small cohort of Ap-let interneurons regulates larval ecdysis behavior by secretion of an unidentified amidated peptide(s). This hypothesis further predicts that the production of the Ap-let neuropeptide(s) is dependent on each of four specific enzymes, and that a certain aspect(s) of its production and/or release is regulated by dopamine input.
    Developmental Biology 06/2004; 269(1):95-108. · 3.87 Impact Factor
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    ABSTRACT: Octopamine is a major monoamine in invertebrates and affects many physiological processes ranging from energy metabolism to complex behaviors. Octopamine binds to receptors located on various cell types and activates distinct signal transduction pathways to produce these diverse effects. We previously identified one of the Drosophila octopamine receptors named OAMB that produces increases in cAMP and intracellular Ca2+ upon ligand binding. It is expressed at high levels in the brain. To explore OAMB's physiological roles, we generated deletions in the OAMB locus. The resultant oamb mutants were viable without gross anatomical defects. The oamb females displayed normal courtship and copulation; however, they were impaired in ovulation with many mature eggs retained in their ovaries. RT-PCR, in situ hybridization, and expression of a reporter gene revealed that OAMB was also expressed in the thoracicoabdominal ganglion, the female reproductive system, and mature eggs in the ovary. Moreover, analysis of various alleles pinpointed the requirement for OAMB in the body, but not in the brain, for female fecundity. The novel expression pattern of OAMB and its genetic resource described in this study will help advance our understanding on how the neuromodulatory or endocrine system controls reproductive physiology and behavior.
    Developmental Biology 01/2004; 264(1):179-90. · 3.87 Impact Factor
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    ABSTRACT: The diverse physiological effects of dopamine are mediated by multiple receptor systems. The dDA1 represents one of the Drosophila dopamine receptors that activate the cAMP cascade. To gain insight into the role of dDA1, we generated a polyclonal antibody against the unique sequence in dDA1 and investigated dDA1 distribution in the central nervous system (CNS) of Drosophila melanogaster. In both larval and adult CNS pronounced dDA1 immunoreactivity was present in the neuropil of the mushroom bodies, a brain structure crucial for learning and memory in insects, and four unpaired neurons in each thoracic segment. In addition, the larval abdominal ganglion contained two dDA1 cells in each segment. This expression pattern appeared to be maintained in the condensed adult abdominal ganglion although the precise number and the intensity of staining were somewhat variable. The adult CNS also exhibited intense dDA1 immunoreactivity in the central complex, a structure controlling higher-order motor function, moderate expression in several neurosecretory cells, and weak staining in two unpaired neurons in the mesothoracic neuromere. The dDA1 expression in these areas was only detected in adult, but not in third instar larval CNS.
    Gene Expression Patterns 06/2003; 3(2):237-45. · 1.64 Impact Factor

Publication Stats

400 Citations
69.11 Total Impact Points

Institutions

  • 2010–2013
    • University of Texas at El Paso
      • Department of Biological Sciences
      El Paso, TX, United States
  • 2003–2008
    • Pennsylvania State University
      • Department of Biology
      University Park, MD, United States