Biology subjects

Dacks, A. M.

Publications and source records attributed to Dacks, A. M..

11 recordsLinked to original sources

bioRxiv2026

Divergent co-transmission by a predictive motor circuit modulates auditory processing.

During behavior, an animals movements often stimulate its own sensory receptors. For instance, whether during flight or the production of courtship song, when flies beat their wings they cause mechanosensory disturbances that activate primary auditory neurons in the antennae. However, flight and courtship occur under very different behavioral contexts and temporal-scales. As a consequence, the nervous system contains predictive motor circuits that modify sensory processing in anticipation of self-induced (re-afferent) stimulation. However, it is unclear how information about planned movements can be used to effectively tune specialized sensory processing circuits. Here we describe a predictive motor circuit that releases two transmitters to differentially modify auditory neurons that process sound under different behavioral contexts. In Drosophila, two metathoracic ascending histamine neurons (MtAHNs) become active prior to wing movement and project to the primary auditory network. We found that the MtAHNs co-transmit the neuropeptide Dh44 and histamine, and each suppresses the activity of auditory neurons that are integrated into distinct networks that support escape and courtship, respectively. Additionally, Dh44 has a greater impact on male auditory neurons and suppression by Dh44 occurs over a longer time course than histamine. Disrupting either histamine synthesis or neuropeptide release by the MtAHNs reduces courtship success with an increase in cessation during the wing extension step. Consistent with a role in auditory processing of courtship cues, Dh44 cotransmission is present in Drosophila species that have an auditory component to their courtship displays, but is absent in species that use either purely visual courtship or lack apparent courtship behavior. Finally, the projections of the MtAHNs into auditory centers were missing in snow flies, which are wingless. Our results indicate that divergent cotransmission by predictive motor circuits may represent an efficient means to differentially modulate sensory subnetworks impacted by reafferent feedback.

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bioRxiv2025

Individual olfactory channels shape distinct parameters of sleep architecture

AbstractAcross the animal kingdom, olfactory dysfunction and anosmia have been associated with disruptions in sleep. In the fruit fly Drosophila melanogaster, various studies have demonstrated that broadly inhibiting olfactory receptor neurons (ORNs) similarly disrupts sleep/wake cycles, suggesting that baseline ORN signaling is an integral component of olfactory modulation of sleep. However, due to the diversity of ORNs and combinatorial nature of olfactory processing, many of the cellular and molecular mechanisms by which ORNs modulate sleep remain unclear. In this study, we addressed this gap of knowledge by characterizing the contributions of different ensembles of ORNs, individual ORN types, and a known modulator of ORNs on baseline sleep architecture. We find that the activity of distinct ORN types are important for day and nighttime sleep and heterogeneously shape parameters of sleep architecture. Importantly, the effects of ORN signaling on sleep are adjusted across mating status, suggesting that distinct ORN types are recruited within the context of sleep depending on the demands of the animal. Furthermore, the effects of ORN signaling on sleep are in part shaped by heterogeneous serotonin (5-HT) receptor expression. Together, this work identifies cellular and molecular pathways bridging olfaction and sleep, and helps establish a circuit model that can be used to further characterize the behavioral consequences of sensory dysfunction.

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bioRxiv2025

Connectivity of serotonin neurons reveals a constrained inhibitory subnetwork within the olfactory system.

Inhibitory local interneurons (LNs) play an essential role in sensory processing by refining stimulus representations via a diverse collection of mechanisms. The morphological and physiological traits of individual LN types, as well as their connectivity within sensory networks, enable each LN type to support different computations such as lateral inhibition or gain control and are therefore ideal targets for modulatory neurons to have widespread impacts on network activity. In this study, we combined detailed connectivity analyses, serotonin receptor expression, neurophysiology, and computational modeling to demonstrate the functional impact of serotonin on a constrained LN network in the olfactory system of Drosophila. This subnetwork is composed of three LN types and we describe each of their distinctive morphology, connectivity, biophysical properties and odor response properties. We demonstrate that each LN type expresses different combinations of serotonin receptors and that serotonin differentially impacts the excitability of each LN type. Finally, by applying these serotonin induced changes in excitability to a computational model that simulates the impact of inhibition exerted by each LN-type, we predict a role for serotonin in adjusting the dynamic range of antennal lobe output neurons and in noise reduction in odor representations. Thus, a single modulatory system can differentially impact LN types that subserve distinct roles within the olfactory system. Significance StatementInhibitory interneurons refine information processing within sensory networks by enforcing distinct local computations. They are therefore ideal targets for modulatory neurons to efficiently alter sensory processing by up- or downregulating the computations each interneuron class subserves. We identify an interconnected network of three interneuron types in the olfactory system of Drosophila that receive a large amount of serotonergic synaptic input. Each interneuron type differs in their biophysical and response properties and serotonin differentially impacts their excitability. Finally, using a computational model, we predict that the combined effects of serotonin on these inhibitory neurons enables noise reduction in the olfactory system. Thus, modulation of individual cell types collectively adjusts distinct network computations to enable flexible sensory coding.

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bioRxiv2025

Selective life-long suppression of an odor processing channel in response to critical period experience

Sensory circuits undergo experience-dependent plasticity during early-life critical periods, attuning the nervous system to levels of key environmental stimuli. During a critical period in the Drosophila olfactory system, we found that exposure to ethyl butyrate (EB) induces glial phagocytosis of odorant receptor Or42a-positive olfactory sensory neuron (OSN) axon terminals which terminate in the VM7 glomerulus (Leier and Foden et al., 2025). Here, we extend these findings by establishing functional significance and circuit selectivity in this critical period paradigm. First, using a combination of two-photon Ca2+ imaging and the genetically-encoded voltage indicator ASAP5, we find that Or42a OSN odor-evoked responses are permanently suppressed in animals with critical period odor exposure. Thus, critical period odor exposure results in long-term changes to odor sensitivity in Or42a OSNs. Second, to establish the selectivity of glial pruning for Or42a axon terminals, we examined projection neurons (PNs) postsynaptic to Or42a OSNs as well as a second population of highly EB-responsive OSNs, called Or43b OSNs. We find that (1) within VM7, glial pruning is selective for Or42a terminals, and (2) while Or43b OSNs appear modestly pruned, they maintain their sensitivity to EB. To elucidate this difference, we turned to the Drosophila connectome. We identify striking differences in the scale of inhibitory connectivity to Or42a and Or43b OSNs, suggesting that Or42a OSNs may play a particularly central role in EB odor processing. This study expands our understanding of this critical period plasticity paradigm by demonstrating life-long suppression of pruned Or42a OSNs and establishing its specificity within and between sensory circuits.

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bioRxiv2024

Serotonin acts through multiple cellular targets during an olfactory critical period.

Serotonin (5-HT) is known to modulate early development during critical periods when experience drives heightened levels of plasticity in neurons. Here, we take advantage of the genetically tractable olfactory system of Drosophila to investigate how 5-HT modulates critical period plasticity in the CO2 sensing circuit of fruit flies. Our study reveals that 5HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit. The olfactory CPP is known to involve local inhibitory networks and consistent with this we found that knocking down 5-HT7 receptors in a subset of GABAergic local interneurons was sufficient to block CPP, as was knocking down GABA receptors expressed by olfactory sensory neurons (OSNs). Additionally, direct modulation of OSNs via 5-HT2B expression in the cognate OSNs sensing CO2 is also essential for CPP. Furthermore, 5-HT1B expression by serotonergic neurons in the olfactory system is also required during the critical period. Our study reveals that 5-HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit.

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bioRxiv2023

Stimulus-Specific Modulation is Enabled by Differential Serotonin Receptor Expression

Neural networks must be able to flexibly process information under different conditions. To this end, networks frequently rely on uniform expression of modulatory receptors by distinct classes of neurons to fine tune the computations supported by each neuronal class. In this study, we explore the consequences of heterogeneous, rather than uniform, serotonin (5-HT) receptor expression within a cell class for olfactory processing in Drosophila melanogaster. Here, we demonstrate that two distinct populations of olfactory output neurons (projection neurons, PNs) display heterogeneous receptor co-expression of all 5-HT receptors. Moreover, the PN populations that express distinct 5-HT receptors innervate different combinations of glomeruli, implying that the effects of 5-HT on these PNs may vary with their odor tuning. Furthermore, connectomic analyses reveal that PN subsets with different receptor profiles have little convergence upon downstream synaptic partners. Finally, 5-HT differentially modulates the odor-evoked responses of PNs with distinct receptor expression profiles and odor tuning. Overall, this implies that heterogeneous modulatory receptor expression enables differential tuning of activity within a neuronal class depending on the odor scene to which individual neurons respond.

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bioRxiv2023

Organization of an Ascending Circuit that Conveys Flight Motor State

Natural behaviors are a coordinated symphony of motor acts which drive self-induced or reafferent sensory activation. Single sensors only signal presence and magnitude of a sensory cue; they cannot disambiguate exafferent (externally-induced) from reafferent sources. Nevertheless, animals readily differentiate between these sources of sensory signals to make appropriate decisions and initiate adaptive behavioral outcomes. This is mediated by predictive motor signaling mechanisms, which emanate from motor control pathways to sensory processing pathways, but how predictive motor signaling circuits function at the cellular and synaptic level is poorly understood. We use a variety of techniques, including connectomics from both male and female electron microscopy volumes, transcriptomics, neuroanatomical, physiological and behavioral approaches to resolve the network architecture of two pairs of ascending histaminergic neurons (AHNs), which putatively provide predictive motor signals to several sensory and motor neuropil. Both AHN pairs receive input primarily from an overlapping population of descending neurons, many of which drive wing motor output. The two AHN pairs target almost exclusively non-overlapping downstream neural networks including those that process visual, auditory and mechanosensory information as well as networks coordinating wing, haltere, and leg motor output. These results support the conclusion that the AHN pairs multi-task, integrating a large amount of common input, then tile their output in the brain, providing predictive motor signals to non-overlapping sensory networks affecting motor control both directly and indirectly.

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bioRxiv2022

A Neuropeptidergic Signaling Pathway for Olfactory Gain Modulation

Sensory systems are dynamically adjusted according to the animals ongoing needs by neuromodulators, such as neuropeptides. Although many neuropeptides are often widely-distributed throughout sensory networks, it is unclear whether such neuropeptides uniformly modulate network activity. Here, we leverage the numerically tractable primary olfactory center of Drosophila (the antennal lobe, AL) to resolve whether one such widely-distributed neuropeptide (myoinhibitory peptide, MIP) uniformly modulates AL processing. We find that despite being uniformly distributed across the AL, MIP decreases olfactory input to some glomeruli, while simultaneously increasing olfactory input to other glomeruli. We reveal that a heterogeneous ensemble of local interneurons (LNs) are the sole source of MIP within the AL. Through high-resolution connectomic analyses, as well as in vivo physiology, we find that the non-uniform effects of MIP are not likely due to MIPergic LN intrinsic properties (e.g., synaptic inputs/outputs, odor-evoked responses, etc.). Instead, we show that differential expression of the inhibitory MIP receptor (sex peptide receptor, SPR) across glomeruli allows MIP to act on distinct intraglomerular substrates, thus enabling differential modulation of olfactory input. Our findings demonstrate how even a seemingly simple case of modulation (i.e., a single neuropeptide acting through a single receptor) can have complex consequences on network processing by acting non-uniformly within different components of the overall network.

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bioRxiv2020

The wiring logic of an identified serotonergic neuron that spans sensory networks

Serotonergic neurons modulate diverse physiological and behavioral processes in a context-dependent manner, based on their complex connectivity. However, their connectivity has not been comprehensively explored at a single-cell resolution. Using a whole-brain EM dataset we determined the wiring logic of a broadly projecting serotonergic neuron (the "CSDn") in Drosophila. Within the antennal lobe (AL; first-order olfactory region), the CSDn receives glomerulus-specific input and preferentially targets distinct local interneuron subtypes. Furthermore, the wiring logic of the CSDn differs between olfactory regions. The CSDn innervates the AL and lateral horn (LH), yet does not maintain the same synaptic relationship with individual projection neurons that also span both regions. Consistent with this, the CSDn has more distributed connectivity in the LH relative to the AL, preferentially synapsing with principal neuron types based on presumptive transmitter content. Lastly, we identify protocerebral neurons that provide abundant synaptic input to the CSDn. Our study demonstrates how an individual modulatory neuron can interact with local networks and integrate input from non-olfactory sources.

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bioRxiv2019

Serotonergic Modulation of a Visual Microcircuit in Drosophila melanogaster

Sensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing in the face of a highly variable stimulus space. Serotonergic neurons broadly innervate the optic ganglia of Drosophila melanogaster, a widely used model for studying vision. The role for serotonergic signaling in the Drosophila optic lobe and the mechanisms by which serotonin regulates visual neurons remain unclear. Here we map the expression patterns of serotonin receptors in the visual system, focusing on a subset of cells with processes in the first optic ganglion, the lamina, and show that serotonin can modulate visual responses. Serotonin receptors are expressed in several types of columnar cells in the lamina including 5-HT2B in lamina monopolar cell L2, required for the initial steps of visual processing, and both 5-HT1A and 5-HT1B in T1 cells, whose function is unknown. Subcellular mapping with GFP-tagged 5-HT2B and 5-HT1A constructs indicates that these receptors localize to layer M2 of the medulla, proximal to serotonergic boutons, suggesting that the medulla is the primary site of serotonergic regulation for these neurons. Serotonin increases intracellular calcium in L2 terminals in layer M2 and alters the kinetics of visually induced calcium transients in L2 neurons following dark flashes. These effects were not observed in flies without a functional 5-HT2B, which displayed severe differences in the amplitude and kinetics of their calcium response to both dark and light flashes. While we did not detect serotonin receptor expression in L1 neurons, they also undergo serotonin-induced calcium changes, presumably via cell non-autonomous signaling pathways. We provide the first functional data showing a role for serotonergic neuromodulation of neurons required for initiating visual processing in Drosophila and establish a new platform for investigating the serotonergic neuromodulation of sensory networks. Author SummarySerotonergic neurons innervate the Drosophila melanogaster eye, but the function of serotonergic signaling is not known. We found that serotonin receptors are expressed in all neuropils of the optic lobe and identify specific neurons involved in visual information processing that express serotonin receptors. We then demonstrate that activation of these receptors can alter how visual information is processed. These are the first data suggesting a functional role for serotonergic signaling in Drosophila vision. This study contributes to the understanding of serotonin biology and modulation of sensory circuits.

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bioRxiv2017

Transmitter Co-Expression Reveals Key Organizational Principles of Local Interneuron Heterogeneity in the Olfactory System

Heterogeneity of individual neurons within a population expands the computational power of the entire neural network. However, the organizing principles that support heterogeneity within a neuronal class are often poorly understood. Here, we focus on a highly heterogeneous population of local interneurons whose traits co-vary seemingly at random. We asked if local interneurons (LNs) in the antennal lobe (AL) of Manduca sexta express fixed, predictable combinations of neurotransmitters, or if transmitter co-expression can be explained by random probability. We systematically determined the co-expression of neuropeptides and GABA by LNs and found variable patterns of co-expression for all neuropeptides, except for tachykininergic LNs which exhibited highly stereotyped co-expression on a neuron-by-neuron basis. To test if observed patterns of co-expression were random, we used a computational model and found that the probabilities of transmitter co-expression cannot be explained by independent expression of each transmitter. We also determined that setting a single rule in the model, while leaving the rest of the co-expression up to random probability, allowed the model to replicate the overall heterogeneity of transmitter co-expression across antennal lobe LNs. This implies that certain co-expression relationships contribute to the ground plan of the AL, but that otherwise, transmitter expression amongst LNs may be random, allowing heterogeneous co-expression patterns to emerge. Furthermore, neuropeptide receptor expression suggests that peptidergic signaling from LNs may simultaneously target olfactory receptor neurons, LNs and projection neurons, and thus the effects of different peptides do not segregate based on principal AL cell type. Our data suggest that while specific constraints may partially shape transmitter co-expression in LNs, a large amount of flexibility on a neuron-by-neuron basis produces heterogeneous network parameters.

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