Circadian clocks are biochemical time-keeping machines that synchronize animal behavior and physi... more Circadian clocks are biochemical time-keeping machines that synchronize animal behavior and physiology with planetary rhythms. In Drosophila, the core components of the clock comprise a transcription/translation feedback loop and are expressed in seven neuronal clusters in the brain. Although it is increasingly evident that the clocks in each of the neuronal clusters are regulated differently, how these clocks communicate with each other across the circadian neuronal network is less clear. Here, we review the latest evidence that describes the physical connectivity of the circadian neuronal network . Using small ventral lateral neurons as a starting point, we summarize how one clock may communicate with another, highlighting the signaling pathways that are both upstream and downstream of these clocks. We propose that additional efforts are required to understand how temporal information generated in each circadian neuron is integrated across a neuronal circuit to regulate rhythmic b...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 23, 2016
Circadian clocks enable organisms to anticipate and adapt to fluctuating environmental conditions... more Circadian clocks enable organisms to anticipate and adapt to fluctuating environmental conditions. Despite substantial knowledge of central clock machineries, we have less understanding of how the central clock's behavioral outputs are regulated. Here, we identifyDrosophilamiR-124 as a critical regulator of diurnal activity. During normal light/dark cycles,mir-124mutants exhibit profoundly abnormal locomotor activity profiles, including loss of anticipatory capacities at morning and evening transitions. Moreover,mir-124mutants exhibited striking behavioral alterations in constant darkness (DD), including a temporal advance in peak activity. Nevertheless, anatomical and functional tests demonstrate a normal circadian pacemaker inmir-124mutants, indicating this miRNA regulates clock output. Among the extensive miR-124 target network, heterozygosity for targets in the BMP pathway substantially corrected the evening activity phase shift in DD. Thus, excess BMP signaling drives speci...
Proceedings of the National Academy of Sciences of the United States of America, 2015
Recent studies have identified molecular pathways driving forgetting and supported the notion tha... more Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β'1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also sugges...
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
MicroRNA (miRNA)-mediated gene regulation plays a key role in brain development and function. But... more MicroRNA (miRNA)-mediated gene regulation plays a key role in brain development and function. But there are few cases in which the roles of individual miRNAs have been elucidated in behaving animals. We report a miR-276a::DopR regulatory module in Drosophila that functions in distinct circuits for naive odor responses and conditioned odor memory. Drosophila olfactory aversive memory involves convergence of the odors (conditioned stimulus) and the electric shock (unconditioned stimulus) in mushroom body (MB) neurons. Dopamine receptor DopR mediates the unconditioned stimulus inputs onto MB. Distinct dopaminergic neurons also innervate ellipsoid body (EB), where DopR function modulates arousal to external stimuli. We demonstrate that miR-276a is required in MB neurons for memory formation and in EB for naive responses to odors. Both roles of miR-276a are mediated by tuning DopR expression. The dual role of this miR-276a::DopR genetic module in these two neural circuits highlights the ...
Circadian clocks are biochemical time-keeping machines that synchronize animal behavior and physi... more Circadian clocks are biochemical time-keeping machines that synchronize animal behavior and physiology with planetary rhythms. In Drosophila, the core components of the clock comprise a transcription/translation feedback loop and are expressed in seven neuronal clusters in the brain. Although it is increasingly evident that the clocks in each of the neuronal clusters are regulated differently, how these clocks communicate with each other across the circadian neuronal network is less clear. Here, we review the latest evidence that describes the physical connectivity of the circadian neuronal network . Using small ventral lateral neurons as a starting point, we summarize how one clock may communicate with another, highlighting the signaling pathways that are both upstream and downstream of these clocks. We propose that additional efforts are required to understand how temporal information generated in each circadian neuron is integrated across a neuronal circuit to regulate rhythmic b...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 23, 2016
Circadian clocks enable organisms to anticipate and adapt to fluctuating environmental conditions... more Circadian clocks enable organisms to anticipate and adapt to fluctuating environmental conditions. Despite substantial knowledge of central clock machineries, we have less understanding of how the central clock's behavioral outputs are regulated. Here, we identifyDrosophilamiR-124 as a critical regulator of diurnal activity. During normal light/dark cycles,mir-124mutants exhibit profoundly abnormal locomotor activity profiles, including loss of anticipatory capacities at morning and evening transitions. Moreover,mir-124mutants exhibited striking behavioral alterations in constant darkness (DD), including a temporal advance in peak activity. Nevertheless, anatomical and functional tests demonstrate a normal circadian pacemaker inmir-124mutants, indicating this miRNA regulates clock output. Among the extensive miR-124 target network, heterozygosity for targets in the BMP pathway substantially corrected the evening activity phase shift in DD. Thus, excess BMP signaling drives speci...
Proceedings of the National Academy of Sciences of the United States of America, 2015
Recent studies have identified molecular pathways driving forgetting and supported the notion tha... more Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β'1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also sugges...
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
MicroRNA (miRNA)-mediated gene regulation plays a key role in brain development and function. But... more MicroRNA (miRNA)-mediated gene regulation plays a key role in brain development and function. But there are few cases in which the roles of individual miRNAs have been elucidated in behaving animals. We report a miR-276a::DopR regulatory module in Drosophila that functions in distinct circuits for naive odor responses and conditioned odor memory. Drosophila olfactory aversive memory involves convergence of the odors (conditioned stimulus) and the electric shock (unconditioned stimulus) in mushroom body (MB) neurons. Dopamine receptor DopR mediates the unconditioned stimulus inputs onto MB. Distinct dopaminergic neurons also innervate ellipsoid body (EB), where DopR function modulates arousal to external stimuli. We demonstrate that miR-276a is required in MB neurons for memory formation and in EB for naive responses to odors. Both roles of miR-276a are mediated by tuning DopR expression. The dual role of this miR-276a::DopR genetic module in these two neural circuits highlights the ...
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Papers by Wanhe Li