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A single pair of neurons links sleep to memory consolidation in Drosophila melanogaster.

Haynes PR, Christmann BL, Griffith LC - Elife (2015)

Bottom Line: Downregulation of α'/β' GABAA and GABABR3 receptors results in sleep loss, suggesting these receptors are the sleep-relevant targets of DPM-mediated inhibition.Regulation of sleep by neurons necessary for consolidation suggests that these brain processes may be functionally interrelated via their shared anatomy.These findings have important implications for the mechanistic relationship between sleep and memory consolidation, arguing for a significant role of inhibitory neurotransmission in regulating these processes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Volen Center for Complex Systems, National Center for Behavioral Genomics, Brandeis University, Waltham, United States.

ABSTRACT
Sleep promotes memory consolidation in humans and many other species, but the physiological and anatomical relationships between sleep and memory remain unclear. Here, we show the dorsal paired medial (DPM) neurons, which are required for memory consolidation in Drosophila, are sleep-promoting inhibitory neurons. DPMs increase sleep via release of GABA onto wake-promoting mushroom body (MB) α'/β' neurons. Functional imaging demonstrates that DPM activation evokes robust increases in chloride in MB neurons, but is unable to cause detectable increases in calcium or cAMP. Downregulation of α'/β' GABAA and GABABR3 receptors results in sleep loss, suggesting these receptors are the sleep-relevant targets of DPM-mediated inhibition. Regulation of sleep by neurons necessary for consolidation suggests that these brain processes may be functionally interrelated via their shared anatomy. These findings have important implications for the mechanistic relationship between sleep and memory consolidation, arguing for a significant role of inhibitory neurotransmission in regulating these processes.

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MB α’β’ neuron activity promotes wakefulness.The α’β’ c305a-GAL4 driver line was crossed to UAS-dTrpA1-II (with c305a expression restricted to the MB) to determine effects on sleep of α’β’ activation. (A) shows sleep in 30-min bins during a baseline day (22°C), followed by 2 days of DPM hyperactivation (31°C) and 1 day of recovery (22°C). (B) shows minutes of sleep gained or lost by the experimental genotype in comparison to either the UAS or GAL4 control genotypes during heating and recovery periods. MB-restricted genotypes are: 1). UAS-dTrpA1, ptub>GAL80>/c305a-GAL4; MB-LexA/LexAop-Flp, 2). c305a-GAL4; MB-LexA (GAL4/LexA control), and 3). UAS-dTrpA1, ptub>GAL80>; LexAop-Flp (UAS/LexAOP control). Grey shading indicates the dark period/night, red bars indicate increased temperature. All data are presented as mean ± SEM where * represents p < 0.05, **p < 0.001 and ***p < 0.0001 using the Mann-Whitney-Wilcoxon rank sum test. Calculation of sleep gain or loss and statistics are described in the ‘Materials and methods’ section.DOI:http://dx.doi.org/10.7554/eLife.03868.009
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fig2: MB α’β’ neuron activity promotes wakefulness.The α’β’ c305a-GAL4 driver line was crossed to UAS-dTrpA1-II (with c305a expression restricted to the MB) to determine effects on sleep of α’β’ activation. (A) shows sleep in 30-min bins during a baseline day (22°C), followed by 2 days of DPM hyperactivation (31°C) and 1 day of recovery (22°C). (B) shows minutes of sleep gained or lost by the experimental genotype in comparison to either the UAS or GAL4 control genotypes during heating and recovery periods. MB-restricted genotypes are: 1). UAS-dTrpA1, ptub>GAL80>/c305a-GAL4; MB-LexA/LexAop-Flp, 2). c305a-GAL4; MB-LexA (GAL4/LexA control), and 3). UAS-dTrpA1, ptub>GAL80>; LexAop-Flp (UAS/LexAOP control). Grey shading indicates the dark period/night, red bars indicate increased temperature. All data are presented as mean ± SEM where * represents p < 0.05, **p < 0.001 and ***p < 0.0001 using the Mann-Whitney-Wilcoxon rank sum test. Calculation of sleep gain or loss and statistics are described in the ‘Materials and methods’ section.DOI:http://dx.doi.org/10.7554/eLife.03868.009

Mentions: To address this issue, we acutely activated these neurons with an MB-restricted version of the α’/β’ driver line c305a-GAL4 and the warmth-sensitive cation channel, dTrpA1. If DPM neurons act to excite α’/β’, as postulated by models of consolidation, we would expect this manipulation to increase sleep. Instead, we see a strong decrease in nighttime sleep. This α’/β’–dependent nighttime sleep loss remained stable throughout 48 hr of dTrpA1 activation and was accompanied by increasing daytime sleep loss which continued even after release from dTrpA1 activation (Figure 2A,C). This unusual pattern exactly matches the phenotype seen in flies expressing Shits in DPM neurons. Thus, DPM and α’/β’ activity have opposing roles in the regulation of sleep: DPM activity promotes sleep whereas α’/β’ activity is wake-promoting. These data suggest that DPM neurons may inhibit MB neurons.10.7554/eLife.03868.009Figure 2.MB α’β’ neuron activity promotes wakefulness.


A single pair of neurons links sleep to memory consolidation in Drosophila melanogaster.

Haynes PR, Christmann BL, Griffith LC - Elife (2015)

MB α’β’ neuron activity promotes wakefulness.The α’β’ c305a-GAL4 driver line was crossed to UAS-dTrpA1-II (with c305a expression restricted to the MB) to determine effects on sleep of α’β’ activation. (A) shows sleep in 30-min bins during a baseline day (22°C), followed by 2 days of DPM hyperactivation (31°C) and 1 day of recovery (22°C). (B) shows minutes of sleep gained or lost by the experimental genotype in comparison to either the UAS or GAL4 control genotypes during heating and recovery periods. MB-restricted genotypes are: 1). UAS-dTrpA1, ptub>GAL80>/c305a-GAL4; MB-LexA/LexAop-Flp, 2). c305a-GAL4; MB-LexA (GAL4/LexA control), and 3). UAS-dTrpA1, ptub>GAL80>; LexAop-Flp (UAS/LexAOP control). Grey shading indicates the dark period/night, red bars indicate increased temperature. All data are presented as mean ± SEM where * represents p < 0.05, **p < 0.001 and ***p < 0.0001 using the Mann-Whitney-Wilcoxon rank sum test. Calculation of sleep gain or loss and statistics are described in the ‘Materials and methods’ section.DOI:http://dx.doi.org/10.7554/eLife.03868.009
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fig2: MB α’β’ neuron activity promotes wakefulness.The α’β’ c305a-GAL4 driver line was crossed to UAS-dTrpA1-II (with c305a expression restricted to the MB) to determine effects on sleep of α’β’ activation. (A) shows sleep in 30-min bins during a baseline day (22°C), followed by 2 days of DPM hyperactivation (31°C) and 1 day of recovery (22°C). (B) shows minutes of sleep gained or lost by the experimental genotype in comparison to either the UAS or GAL4 control genotypes during heating and recovery periods. MB-restricted genotypes are: 1). UAS-dTrpA1, ptub>GAL80>/c305a-GAL4; MB-LexA/LexAop-Flp, 2). c305a-GAL4; MB-LexA (GAL4/LexA control), and 3). UAS-dTrpA1, ptub>GAL80>; LexAop-Flp (UAS/LexAOP control). Grey shading indicates the dark period/night, red bars indicate increased temperature. All data are presented as mean ± SEM where * represents p < 0.05, **p < 0.001 and ***p < 0.0001 using the Mann-Whitney-Wilcoxon rank sum test. Calculation of sleep gain or loss and statistics are described in the ‘Materials and methods’ section.DOI:http://dx.doi.org/10.7554/eLife.03868.009
Mentions: To address this issue, we acutely activated these neurons with an MB-restricted version of the α’/β’ driver line c305a-GAL4 and the warmth-sensitive cation channel, dTrpA1. If DPM neurons act to excite α’/β’, as postulated by models of consolidation, we would expect this manipulation to increase sleep. Instead, we see a strong decrease in nighttime sleep. This α’/β’–dependent nighttime sleep loss remained stable throughout 48 hr of dTrpA1 activation and was accompanied by increasing daytime sleep loss which continued even after release from dTrpA1 activation (Figure 2A,C). This unusual pattern exactly matches the phenotype seen in flies expressing Shits in DPM neurons. Thus, DPM and α’/β’ activity have opposing roles in the regulation of sleep: DPM activity promotes sleep whereas α’/β’ activity is wake-promoting. These data suggest that DPM neurons may inhibit MB neurons.10.7554/eLife.03868.009Figure 2.MB α’β’ neuron activity promotes wakefulness.

Bottom Line: Downregulation of α'/β' GABAA and GABABR3 receptors results in sleep loss, suggesting these receptors are the sleep-relevant targets of DPM-mediated inhibition.Regulation of sleep by neurons necessary for consolidation suggests that these brain processes may be functionally interrelated via their shared anatomy.These findings have important implications for the mechanistic relationship between sleep and memory consolidation, arguing for a significant role of inhibitory neurotransmission in regulating these processes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Volen Center for Complex Systems, National Center for Behavioral Genomics, Brandeis University, Waltham, United States.

ABSTRACT
Sleep promotes memory consolidation in humans and many other species, but the physiological and anatomical relationships between sleep and memory remain unclear. Here, we show the dorsal paired medial (DPM) neurons, which are required for memory consolidation in Drosophila, are sleep-promoting inhibitory neurons. DPMs increase sleep via release of GABA onto wake-promoting mushroom body (MB) α'/β' neurons. Functional imaging demonstrates that DPM activation evokes robust increases in chloride in MB neurons, but is unable to cause detectable increases in calcium or cAMP. Downregulation of α'/β' GABAA and GABABR3 receptors results in sleep loss, suggesting these receptors are the sleep-relevant targets of DPM-mediated inhibition. Regulation of sleep by neurons necessary for consolidation suggests that these brain processes may be functionally interrelated via their shared anatomy. These findings have important implications for the mechanistic relationship between sleep and memory consolidation, arguing for a significant role of inhibitory neurotransmission in regulating these processes.

Show MeSH
Related in: MedlinePlus