Journal
JOURNAL OF NEUROSCIENCE
Volume 40, Issue 50, Pages 9617-9633Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1488-20.2020
Keywords
cAMP; clock neurons; dopamine; patch-clamp recording; sleep; wakefulness
Categories
Funding
- German Research Foundation [Fo207/14-1, PA3241/2-1]
- Agencia Nacional de Promocion de la Investigacion, el Desarrollo Tecnologico y la Innovacion Grant [PICT-2015-2557]
- FOCEM-Mercosur Grant [COF 03/11]
- National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01-NS-077933]
- National Science Foundation IOS (Integrative Organismal Systems) [1354046]
- Direct For Biological Sciences [1354046] Funding Source: National Science Foundation
- Division Of Integrative Organismal Systems [1354046] Funding Source: National Science Foundation
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Dopamine is a wake-promoting neuromodulator in mammals and fruit flies. In Drosophila melanogaster, the network of clock neurons that drives sleep/activity cycles comprises both wake-promoting and sleep-promoting cell types. The large ventrolateral neurons (l-LN(v)s) and small ventrolateral neurons (s-LN(v)s) have been identified as wake-promoting neurons within the clock neuron network. The 1-LN(v)s are innervated by dopaminergic neurons, and earlier work proposed that dopamine signaling raises cAMP levels in the l-LNvS and thus induces excitatory electrical activity (action potential firing), which results in wakefulness and inhibits sleep. Here, we test this hypothesis by combining cAMP imaging and patch-clamp recordings in isolated brains. We find that dopamine application indeed increases cAMP levels and depolarizes the I-LN(v)s, but, surprisingly, it does not result in increased firing rates. Downregulation of the excitatory D-1-like dopamine receptor (DopIR1) in the l-LNys and s-LN(v)s, but not of Dop1R2, abolished the depolarization of l-LNvvs in response to dopamine. This indicates that dopamine signals via Dop1R1 to the l-LN(v)s. Downregulation of Dop1R1 or Dop1R2 in the I-LN(v)s and s-LN(v)s does not affect sleep in males. Unexpectedly, we find a moderate decrease of daytime sleep with downregulation of DopIRI and of nighttime sleep with downregulation of Dop1R2. Since the I-LN(v)s do not use Dop1R2 receptors and the s-LN(v)s also respond to dopamine, we conclude that the s-LN(v)s are responsible for the observed decrease in nighttime sleep. In summary, dopamine signaling in the wake-promoting LN(v)s is not required for daytime arousal, but likely promotes nighttime sleep via the s-LN(v)s.
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