Acute control of the sleep switch in Drosophila reveals a role for gap junctions in regulating behavioral responsiveness
Sleep is a dynamic process in most animals, involving distinct stages that probably achieve multiple functions for the brain. Before sleep functions can be initiated, it is likely that behavioral responsiveness to the outside world needs to be reduced first, even while animals are still awake. Recent work in Drosophila has uncovered a sleep switch in the dorsal fan-shaped body (dFB) of the fly's central brain, but it is unknown if these sleep-promoting neurons also govern the acute need to ignore salient stimuli in the environment during sleep transitions. We found that optogenetic activation of the sleep switch suppressed behavioral responsiveness to mechanical stimuli, even in awake flies, indicating a broader role for these neurons in regulating arousal. The dFB-mediated suppression mechanism and its associated neural correlates requires innexin6 expression, suggesting that the acute need to reduce sensory perception when flies fall asleep is mediated in part by electrical synapses.
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
National Institutes of Health (R01 NS076980)
- Melvyn HW Yap
- Paul Shaw
- Bruno van Swinderen
National Health and Medical Research Council (GNT1065713)
- Michael Troup
- Chelsie Rohrscheib
- Aoife Larkin
- Bruno van Swinderen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Mani Ramaswami, Trinity College Dublin, Ireland
- Received: April 22, 2018
- Accepted: August 14, 2018
- Accepted Manuscript published: August 15, 2018 (version 1)
- Version of Record published: August 30, 2018 (version 2)
© 2018, Troup et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
- Page views
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
- Computational and Systems Biology
Inhibition is crucial for brain function, regulating network activity by balancing excitation and implementing gain control. Recent evidence suggests that beyond simply inhibiting excitatory activity, inhibitory neurons can also shape circuit function through disinhibition. While disinhibitory circuit motifs have been implicated in cognitive processes including learning, attentional selection, and input gating, the role of disinhibition is largely unexplored in the study of decision-making. Here, we show that disinhibition provides a simple circuit motif for fast, dynamic control of network state and function. This dynamic control allows a disinhibition-based decision model to reproduce both value normalization and winner-take-all dynamics, the two central features of neurobiological decision-making captured in separate existing models with distinct circuit motifs. In addition, the disinhibition model exhibits flexible attractor dynamics consistent with different forms of persistent activity seen in working memory. Fitting the model to empirical data shows it captures well both the neurophysiological dynamics of value coding and psychometric choice behavior. Furthermore, the biological basis of disinhibition provides a simple mechanism for flexible top-down control of the network states, enabling the circuit to capture diverse task-dependent neural dynamics. These results suggest a biologically plausible unifying mechanism for decision-making and emphasize the importance of local disinhibition in neural processing.
The available treatments for depression have substantial limitations, including low response rates and substantial lag time before a response is achieved. We applied deep brain stimulation (DBS) to the lateral habenula (LHb) of two rat models of depression (Wistar Kyoto rats and lipopolysaccharide-treated rats) and observed an immediate (within seconds to minutes) alleviation of depressive-like symptoms with a high-response rate. Simultaneous functional MRI (fMRI) conducted on the same sets of depressive rats used in behavioral tests revealed DBS-induced activation of multiple regions in afferent and efferent circuitry of the LHb. The activation levels of brain regions connected to the medial LHb (M-LHb) were correlated with the extent of behavioral improvements. Rats with more medial stimulation sites in the LHb exhibited greater antidepressant effects than those with more lateral stimulation sites. These results indicated that the antidromic activation of the limbic system and orthodromic activation of the monoaminergic systems connected to the M-LHb played a critical role in the rapid antidepressant effects of LHb-DBS. This study indicates that M-LHb-DBS might act as a valuable, rapid-acting antidepressant therapeutic strategy for treatment-resistant depression and demonstrates the potential of using fMRI activation of specific brain regions as biomarkers to predict and evaluate antidepressant efficacy.