Taste quality and hunger interactions in a feeding sensorimotor circuit
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Evaluation Summary:
This manuscript contributes to a circuit-based understanding of how sweet and bitter tastes are integrated with hunger state to drive feeding initiation in Drosophila. Anatomical, behavioral, and neuronal activity data support a multi-step pathway from sensory input to motor output. This manuscript, thus, contributes to our understanding of how multiple sensory cues are integrated with an internal state to reach a behavioral decision.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)
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Abstract
Taste detection and hunger state dynamically regulate the decision to initiate feeding. To study how context-appropriate feeding decisions are generated, we combined synaptic resolution circuit reconstruction with targeted genetic access to specific neurons to elucidate a gustatory sensorimotor circuit for feeding initiation in adult Drosophila melanogaster . This circuit connects gustatory sensory neurons to proboscis motor neurons through three intermediate layers. Most neurons in this pathway are necessary and sufficient for proboscis extension, a feeding initiation behavior, and respond selectively to sugar taste detection. Pathway activity is amplified by hunger signals that act at select second-order neurons to promote feeding initiation in food-deprived animals. In contrast, the feeding initiation circuit is inhibited by a bitter taste pathway that impinges on premotor neurons, illuminating a local motif that weighs sugar and bitter taste detection to adjust the behavioral outcomes. Together, these studies reveal central mechanisms for the integration of external taste detection and internal nutritive state to flexibly execute a critical feeding decision.
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Evaluation Summary:
This manuscript contributes to a circuit-based understanding of how sweet and bitter tastes are integrated with hunger state to drive feeding initiation in Drosophila. Anatomical, behavioral, and neuronal activity data support a multi-step pathway from sensory input to motor output. This manuscript, thus, contributes to our understanding of how multiple sensory cues are integrated with an internal state to reach a behavioral decision.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)
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Reviewer #1 (Public Review):
While the peripheral taste system in the fruit fly is comparably well understood, the corresponding neural circuit are still less explored. Using EM-based connectomic, optogenetic activation and inhibition as well as Calcium imaging the current manuscript provides insight into the functional organization of the sugar-taste circuit and its connection towards motoneurons. The current manuscript provides a leap in understanding early circuits of taste processing using these two parallel approaches connectomics and neurogenetics.
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Reviewer #2 (Public Review):
This is elegant circuit mapping. The neurons that detect sweet taste, some command-like neurons, dopaminergic modulator neurons, and most proboscis motor neurons were known, but the current work uses electron microscopy data for neuronal reconstructions and optogenetic activation with functional imaging to reveal that the circuit connectivity is quite complex. The behavioral experiments demonstrate which components are sufficient, which are necessary, showing greater flexibility than might have been anticipated. The ability to determine where bitter taste and hunger affect the circuit using optogenetic activation (bypassing the known modulation at the sensory layer) and comparison of proboscis extension in fed and starved flies is especially nice. The functional imaging demonstrates which second and …
Reviewer #2 (Public Review):
This is elegant circuit mapping. The neurons that detect sweet taste, some command-like neurons, dopaminergic modulator neurons, and most proboscis motor neurons were known, but the current work uses electron microscopy data for neuronal reconstructions and optogenetic activation with functional imaging to reveal that the circuit connectivity is quite complex. The behavioral experiments demonstrate which components are sufficient, which are necessary, showing greater flexibility than might have been anticipated. The ability to determine where bitter taste and hunger affect the circuit using optogenetic activation (bypassing the known modulation at the sensory layer) and comparison of proboscis extension in fed and starved flies is especially nice. The functional imaging demonstrates which second and third-order neurons respond to the activation of sweet taste neurons. As the authors are careful to point out, this is a circuit, not the circuit: there are likely additional pathways connecting taste sensation and feeding control, so there remains more to discover in this rich system.
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Reviewer #3 (Public Review):
The authors are attempting to provide an extensive anatomical map of the circuits that promote feeding initiation, identify genetic tools to manipulate individual circuit elements, and then use these tools to begin to directly link the (mostly) newly identified circuit elements to behavior.
The paper has many strengths: In the first section of the paper, the authors provide a connectome of the neural circuit that drives proboscis extension upon activation of sweet-response gustatory receptor neurons (GRNs) in the Drosophila melanogaster labellum. They also identify a companion set of genetic tools that permits cell-specific physiological analysis and activity manipulation of many of the individual neurons within the circuit. Together these advances mark a quantum leap, greatly expanding our knowledge of the …
Reviewer #3 (Public Review):
The authors are attempting to provide an extensive anatomical map of the circuits that promote feeding initiation, identify genetic tools to manipulate individual circuit elements, and then use these tools to begin to directly link the (mostly) newly identified circuit elements to behavior.
The paper has many strengths: In the first section of the paper, the authors provide a connectome of the neural circuit that drives proboscis extension upon activation of sweet-response gustatory receptor neurons (GRNs) in the Drosophila melanogaster labellum. They also identify a companion set of genetic tools that permits cell-specific physiological analysis and activity manipulation of many of the individual neurons within the circuit. Together these advances mark a quantum leap, greatly expanding our knowledge of the circuitry that drives the initiation of feeding in the fly. Identifying so many of the neurons involved and providing a wiring diagram describing their contacts will be of great interest to the field and an important reference work. Furthermore, the cell-specific genetic tools identified in this paper will also be of tremendous utility to the field. One anticipates that this manuscript will be foundational for many subsequent studies of taste processing in the fly.
Having laid this initial groundwork, the authors then begin to interrogate the circuit functionally and examine multiple aspects of taste processing. The work presented in these sections is clear and the data are convincing, but the large number of neurons under consideration and the variety of phenomena examined makes it a bit scattered and unwieldy in parts. To take the topics in order: The authors first examine the necessity of individual identified neurons in this circuit for the proboscis extension response (PER) upon tastant detection (sucrose) as well as the sufficiency of activation of individual circuit elements to drive proboscis extension. They then assess how gustatory neuron activation modulates the activity of these brain neurons and how hunger modulates their ability to drive proboscis extension. Finally, the authors identify a pre-motor neuron as a site of intersection between the sweet and bitter detection pathways that can mediate the inhibitory effects of bitter compounds on PER centrally. Together these experiments demonstrate convincingly that the neuronal elements under investigation are indeed important for controlling feeding initiation (PER) behavior and that (most) of these neurons respond to the gustatory neuron activation as expected. They also begin to define specific neurons in the brain that are targeted by modulatory interactions in the form of bitter perception and physiological state.
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