Inhibitory control of locomotor statistics in walking Drosophila.

In order to forage for food, many animals regulate not only specific limb movements but the statistics of locomotor behavior over time, for example switching between long-range dispersal behaviors and more localized search depending on the availability of resources. How pre-motor circuits regulate such locomotor statistics is not clear. Here we took advantage of the robust changes in locomotor statistics evoked by attractive odors in walking Drosophila to investigate their neural control. We began by analyzing the statistics of ground speed and angular velocity during three well-defined motor regimes: baseline walking, upwind running during odor, and search behavior following odor offset. We find that during search behavior, flies adopt higher angular velocities and slower ground speeds, and tend to turn for longer periods of time in one direction. We further find that flies spontaneously adopt periods of different mean ground speed, and that these changes in state influence the length of odor-evoked runs. We next developed a simple physiologically-inspired computational model of locomotor control that can recapitulate these statistical features of fly locomotion. Our model suggests that contralateral inhibition plays a key role both in regulating the difference between baseline and search behavior, and in modulating the response to odor with ground speed. As the fly connectome predicts decussating inhibitory neurons in the lateral accessory lobe (LAL), a pre-motor structure, we generated genetic tools to target these neurons and test their role in behavior. Consistent with our model, we found that activation of neurons labeled in one line increased curvature. In a second line labeling distinct neurons, activation and inactivation strongly and reciprocally regulated ground speed and altered the length of the odor-evoked run. Additional targeted light activation experiments argue that these effects arise from the brain rather than from neurons in the ventral nerve cord, while sparse activation experiments argue that speed control in the second line arises from both LAL neurons and a population of neurons in the dorsal superior medial protocerebrum (SMP). Together, our work develops a biologically plausible computational architecture that captures the statistical features of fly locomotion across behavioral states and identifies potential neural substrates of these computations.

The conserved RNA-binding protein Imp is required for the specification and function of olfactory navigation circuitry in Drosophila.

Complex behaviors depend on the precise developmental specification of neuronal circuits, but the relationship between genetic programs for neural development, circuit structure, and behavioral output is often unclear. The central complex (CX) is a conserved sensory-motor integration center in insects, which governs many higher-order behaviors and largely derives from a small number of type II neural stem cells (NSCs). Here, we show that Imp, a conserved IGF-II mRNA-binding protein expressed in type II NSCs, plays a role in specifying essential components of CX olfactory navigation circuitry. We show the following: (1) that multiple components of olfactory navigation circuitry arise from type II NSCs. (2) Manipulating Imp expression in type II NSCs alters the number and morphology of many of these circuit elements, with the most potent effects on neurons targeting the ventral layers of the fan-shaped body (FB). (3) Imp regulates the specification of Tachykinin-expressing ventral FB input neurons. (4) Imp is required in type II NSCs for establishing proper morphology of the CX neuropil structures. (5) Loss of Imp in type II NSCs abolishes upwind orientation to attractive odor while leaving locomotion and odor-evoked regulation of movement intact. Taken together, our findings establish that a temporally expressed gene can regulate the expression of a complex behavior by developmentally regulating the specification of multiple circuit components and provides a first step toward a developmental dissection of the CX and its roles in behavior.

Astrocyte growth is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor.

Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations, but signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here, we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1 is required for astrocytes to establish their intricate morphology in vivo. The lipid phosphate phosphatases Wunen/Wunen2 also regulate astrocyte morphology and, via Tre1, mediate astrocyte-astrocyte competition for growth-promoting lipids. Loss of s1pr1, the functional analog of Tre1 in zebrafish, disrupts astrocyte process elaboration, and live imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during growth. Loss of Tre1 in flies or S1pr1 in zebrafish results in defects in simple assays of motor behavior. Tre1 and S1pr1 are thus potent evolutionarily conserved regulators of the elaboration of astrocyte morphological complexity and, ultimately, astrocyte control of behavior.

The RNA-binding protein, Imp specifies olfactory navigation circuitry and behavior in Drosophila.

Complex behaviors depend on the precise developmental specification of neuronal circuits, but the relationship between genetic prograssms for neural development, circuit structure, and behavioral output is often unclear. The central complex (CX) is a conserved sensory-motor integration center in insects that governs many higher order behaviors and largely derives from a small number of Type II neural stem cells. Here, we show that Imp, a conserved IGF-II mRNA-binding protein expressed in Type II neural stem cells, specifies components of CX olfactory navigation circuitry. We show: (1) that multiple components of olfactory navigation circuitry arise from Type II neural stem cells and manipulating Imp expression in Type II neural stem cells alters the number and morphology of many of these circuit elements, with the most potent effects on neurons targeting the ventral layers of the fan-shaped body. (2) Imp regulates the specification of Tachykinin expressing ventral fan-shaped body input neurons. (3) Imp in Type II neural stem cells alters the morphology of the CX neuropil structures. (4) Loss of Imp in Type II neural stem cells abolishes upwind orientation to attractive odor while leaving locomotion and odor-evoked regulation of movement intact. Taken together, our work establishes that a single temporally expressed gene can regulate the expression of a complex behavior through the developmental specification of multiple circuit components and provides a first step towards a developmental dissection of the CX and its roles in behavior.

SAMPL is a high-throughput solution to study unconstrained vertical behavior in small animals.

Balance and movement are impaired in many neurological disorders. Recent advances in behavioral monitoring provide unprecedented access to posture and locomotor kinematics but without the throughput and scalability necessary to screen candidate genes/potential therapeutics. Here, we present a scalable apparatus to measure posture and locomotion (SAMPL). SAMPL includes extensible hardware and open-source software with real-time processing and can acquire data from D. melanogaster, C. elegans, and D. rerio as they move vertically. Using SAMPL, we define how zebrafish balance as they navigate vertically and discover small but systematic variations among kinematic parameters between genetic backgrounds. We demonstrate SAMPL's ability to resolve differences in posture and navigation as a function of effect size and data gathered, providing key data for screens. SAMPL is therefore both a tool to model balance and locomotor disorders and an exemplar of how to scale apparatus to support screens.

Active antennal movements in Drosophila can tune wind encoding.

Insects use their antennae to smell odors,1,2 detect auditory cues,3,4 and sense mechanosensory stimuli such as wind5 and objects,6,7,8 frequently by combining sensory processing with active movements. Genetic access to antennal motor systems would therefore provide a powerful tool for dissecting the circuit mechanisms underlying active sensing, but little is known about how the most genetically tractable insect, Drosophila melanogaster, moves its antennae. Here, we use deep learning to measure how tethered Drosophila move their antennae in the presence of sensory stimuli and identify genetic reagents for controlling antennal movement. We find that flies perform both slow adaptive movements and fast flicking movements in response to wind-induced deflections, but not the attractive odor apple cider vinegar. Next, we describe four muscles in the first antennal segment that control antennal movements and identify genetic driver lines that provide access to two groups of antennal motor neurons and an antennal muscle. Through optogenetic inactivation, we provide evidence that antennal motor neurons contribute to active movements with different time courses. Finally, we show that activation of antennal motor neurons and muscles can adjust the gain and acuity of wind direction encoding by antennal displacement. Together, our experiments provide insight into the neural control of antennal movement and suggest that active antennal positioning in Drosophila may tune the precision of wind encoding.

Olfaction: The smell stops here.

A recent study has shown that, in the fly Drosophila, olfactory neurons stop signaling when smells get too strong. This changes the way we think about odor encoding across concentrations.

Olfactory navigation in arthropods.

Using odors to find food and mates is one of the most ancient and highly conserved behaviors. Arthropods from flies to moths to crabs use broadly similar strategies to navigate toward odor sources-such as integrating flow information with odor information, comparing odor concentration across sensors, and integrating odor information over time. Because arthropods share many homologous brain structures-antennal lobes for processing olfactory information, mechanosensors for processing flow, mushroom bodies (or hemi-ellipsoid bodies) for associative learning, and central complexes for navigation, it is likely that these closely related behaviors are mediated by conserved neural circuits. However, differences in the types of odors they seek, the physics of odor dispersal, and the physics of locomotion in water, air, and on substrates mean that these circuits must have adapted to generate a wide diversity of odor-seeking behaviors. In this review, we discuss common strategies and specializations observed in olfactory navigation behavior across arthropods, and review our current knowledge about the neural circuits subserving this behavior. We propose that a comparative study of arthropod nervous systems may provide insight into how a set of basic circuit structures has diversified to generate behavior adapted to different environments.

Scalable Apparatus to Measure Posture and Locomotion (SAMPL): a high-throughput solution to study unconstrained vertical behavior in small animals.

Balance and movement are impaired in a wide variety of neurological disorders. Recent advances in behavioral monitoring provide unprecedented access to posture and locomotor kinematics, but without the throughput and scalability necessary to screen candidate genes / potential therapeutics. We present a powerful solution: a Scalable Apparatus to Measure Posture and Locomotion (SAMPL). SAMPL includes extensible imaging hardware and low-cost open-source acquisition software with real-time processing. We first demonstrate that SAMPL's hardware and acquisition software can acquire data from from D. melanogaster, C. elegans, and D. rerio as they move vertically. Next, we leverage SAMPL's throughput to rapidly (two weeks) gather a new zebrafish dataset. We use SAMPL's analysis and visualization tools to replicate and extend our current understanding of how zebrafish balance as they navigate through a vertical environment. Next, we discover (1) that key kinematic parameters vary systematically with genetic background, and (2) that such background variation is small relative to the changes that accompany early development. Finally, we simulate SAMPL's ability to resolve differences in posture or vertical navigation as a function of affect size and data gathered -- key data for screens. Taken together, our apparatus, data, and analysis provide a powerful solution for labs using small animals to investigate balance and locomotor disorders at scale. More broadly, SAMPL is both an adaptable resource for labs looking process videographic measures of behavior in real-time, and an exemplar of how to scale hardware to enable the throughput necessary for screening.

A neural circuit for wind-guided olfactory navigation.

To navigate towards a food source, animals frequently combine odor cues about source identity with wind direction cues about source location. Where and how these two cues are integrated to support navigation is unclear. Here we describe a pathway to the Drosophila fan-shaped body that encodes attractive odor and promotes upwind navigation. We show that neurons throughout this pathway encode odor, but not wind direction. Using connectomics, we identify fan-shaped body local neurons called h∆C that receive input from this odor pathway and a previously described wind pathway. We show that h∆C neurons exhibit odor-gated, wind direction-tuned activity, that sparse activation of h∆C neurons promotes navigation in a reproducible direction, and that h∆C activity is required for persistent upwind orientation during odor. Based on connectome data, we develop a computational model showing how h∆C activity can promote navigation towards a goal such as an upwind odor source. Our results suggest that odor and wind cues are processed by separate pathways and integrated within the fan-shaped body to support goal-directed navigation.

Statewide evaluation of COVID-19 vaccine hesitancy in Rhode Island.

BACKGROUND: Vaccines are effective in preventing Coronavirus Disease 2019 (COVID-19). Vaccine hesitancy defined as delay of acceptance or refusal of the vaccine is a major barrier to effective implementation. METHODS: Participants were recruited statewide through an English and Spanish social media marketing campaign conducted by a local news station during a one-month period as vaccines were becoming available in Rhode Island (from December 21, 2020 to January 22, 2021). Participants completed an online survey about COVID-19 vaccines and vaccine hesitancy with constructs and items adopted from the Health Belief Model. RESULTS: A total of 2,007 individuals completed the survey. Eight percent (n = 161) reported vaccine hesitancy. The sample had a median age of 58 years (interquartile range [IQR]: 45, 67), were majority female (78%), White (96%), Non-Hispanic (94%), employed (58%), and reported an annual individual income of $50,000 (59%). COVID-19 vaccine hesitancy was associated with attitudes and behaviors related to COVID-19. A one unit increase in concern about COVID-19 was associated with a 69% (Adjusted Odds Ratio: 0.31, 95% CI: 0.26-0.37) decrease in vaccine hesitancy. A one-level increase in the likelihood of getting influenza vaccine was associated with a 55% (AOR: 0.45 95% CI: 0.41-0.50) decrease in vaccine hesitancy. CONCLUSIONS: COVID-19 vaccine hesitancy was relatively low in a state-wide survey in Rhode Island. Future research is needed to better understand and tailor messaging related to vaccine hesitancy.

Motion vision: Pinning down motion computation in an ever-changing circuit.

A new electrophysiological study of the Drosophila visual system, recording from columnar inputs to motion-detecting neurons, has provided new insights into the computations that underlie motion vision.

Characterizing the Impact of COVID-19 on Pre-Exposure Prophylaxis (PrEP) Care.

COVID-19 is a public health crisis that has fundamentally altered health care provision. The purpose of this study was to examine the impact of COVID-19 on pre-exposure prophylaxis (PrEP) care. We reviewed all patient records for those who presented for PrEP care at a PrEP program in Providence, Rhode Island from September 1st, 2019 to May 29th, 2020. The number of PrEP encounters decreased but was not significantly different over time (ps > .05). Patients were still able to access PrEP clinical services during the COVID-19 pandemic. Implementing flexible and timely PrEP delivery approaches in this setting likely minimized the disruption of PrEP care during COVID-19.

RESUMEN: COVID-19 es una crisis de salud pública que ha alterado fundamentalmente la prestación de servicios de salud. El propósito de este estudio fue examinar el impacto de COVID-19 en los servicios de la profilaxis preexposición (PrEP). Revisamos todos los registros de pacientes que se presentaron para recibir atención de PrEP en un programa de PrEP en Providence, Rhode Island desde el 1 de septiembre de 2019 hasta el 29 de mayo de 2020. El número de encuentros de PrEP disminuyó pero no fue significativamente diferente con el paso del tiempo (ps > .05). Los pacientes aún pudieron acceder a los servicios clínicos de PrEP durante la pandemia de COVID-19. La implementación de enfoques de entrega de PrEP que eran flexibles y oportunos en este entorno probablemente minimizó la interrupción de la atención médica de la PrEP durante COVID-19.

Sex Workers and Syndemics: A Population Vulnerable to HIV and COVID-19.

COVID-19 has disproportionately affected vulnerable populations across the U.S. Street-based sex workers are one vulnerable population whose health and impact of COVID-19 have been understudied to date. The goal of this study was to evaluate findings from a community needs assessment with street-based sex workers on impact of COVID-19 on health behaviors and social circumstances. A brief survey was developed at a community-based harm reduction and recovery services organization. Surveys were administered by peer specialists to street-based sex workers during street outreach in April and May 2020. A total of 46 surveys were analyzed. Many individuals reported continuing to do sex work and use substances during the COVID pandemic. Slightly more than a quarter of individuals (n = 13; 28.3%) indicated using personal protective equipment while doing sex work and described challenges to using precautions when working with clients. Individuals had used marijuana (n = 32, 71.1%), cocaine (n = 17, 39.5%), prescription stimulants (n = 9, 21.4%), methamphetamines (n = 5, 11.9%), prescription opioids (n = 12, 27.3%), street opioids (n = 12, 27.3%), sedatives (n = 11, 25.0%), hallucinogens (n = 3, 6.8%), inhalants (n = 3, 7.0%), or some other substance (n = 4, 8.7%) in the past 30 days. About half (48.8%) reported that COVID-19 had a major impact on their lives. This study is among the first to characterize the impact of COVID-19 on street-based sex workers. From a public health standpoint, this group also represents a high-priority population given their vulnerability and close contact with others, which increases the potential for community spread.

Encoding and control of orientation to airflow by a set of Drosophila fan-shaped body neurons.

The insect central complex (CX) is thought to underlie goal-oriented navigation but its functional organization is not fully understood. We recorded from genetically-identified CX cell types in Drosophila and presented directional visual, olfactory, and airflow cues known to elicit orienting behavior. We found that a group of neurons targeting the ventral fan-shaped body (ventral P-FNs) are robustly tuned for airflow direction. Ventral P-FNs did not generate a 'map' of airflow direction. Instead, cells in each hemisphere were tuned to 45° ipsilateral, forming a pair of orthogonal bases. Imaging experiments suggest that ventral P-FNs inherit their airflow tuning from neurons that provide input from the lateral accessory lobe (LAL) to the noduli (NO). Silencing ventral P-FNs prevented flies from selecting appropriate corrective turns following changes in airflow direction. Our results identify a group of CX neurons that robustly encode airflow direction and are required for proper orientation to this stimulus.

Experience- and Context-Dependent Modulation of the Invertebrate Compass System.

How are head direction signals computed and maintained in neural circuits? In this issue of Neuron, Shiozaki et al. (2020) expand our understanding of the fly "compass" network, revealing context- and experience-dependent changes in the multiplexed encoding of head direction and steering maneuvers.

Multisensory control of navigation in the fruit fly.

Spatial navigation is influenced by cues from nearly every sensory modality and thus provides an excellent model for understanding how different sensory streams are integrated to drive behavior. Here we review recent work on multisensory control of navigation in the model organism Drosophila melanogaster, which allows for detailed circuit dissection. We identify four modes of integration that have been described in the literature-suppression, gating, summation, and association-and describe regions of the larval and adult brain that have been implicated in sensory integration. Finally we discuss what circuit architectures might support these different forms of integration. We argue that Drosophila is an excellent model to discover these circuit and biophysical motifs.

Encoding of Wind Direction by Central Neurons in Drosophila.

Wind is a major navigational cue for insects, but how wind direction is decoded by central neurons in the insect brain is unknown. Here we find that walking flies combine signals from both antennae to orient to wind during olfactory search behavior. Movements of single antennae are ambiguous with respect to wind direction, but the difference between left and right antennal displacements yields a linear code for wind direction in azimuth. Second-order mechanosensory neurons share the ambiguous responses of a single antenna and receive input primarily from the ipsilateral antenna. Finally, we identify novel "wedge projection neurons" that integrate signals across the two antennae and receive input from at least three classes of second-order neurons to produce a more linear representation of wind direction. This study establishes how a feature of the sensory environment-wind direction-is decoded by neurons that compare information across two sensors.