Biology subjects

Frighetto, G.

Publications and source records attributed to Frighetto, G..

7 recordsLinked to original sources

bioRxiv2026

Cellular and functional dissection of the octopaminergic system in the Drosophila brain

Octopamine (OA) is a major biogenic amine in the invertebrate nervous system and is often considered a functional analog of vertebrate noradrenaline. Along with its immediate precursor tyramine (TA), OA influences diverse physiological and behavioral processes, including sensory processing and social behavior. However, understanding the neural basis of its multifunctionality has been constrained by the limited genetic access to defined OA/TA neuron types. Here, we present a curated set of transgenic driver strains that provide selective access to nearly all long-range OA/TA cell types in the brain of common fruit flies, Drosophila melanogaster. Using these tools, we map cell-type-specific innervation patterns, compare male and female neuroanatomy, and cross-reference identified neuron types with electron microscopy connectome datasets. As a proof of principle, we show that distinct optic lobe-projecting OA/TA neuron types differentially modulate visually guided behaviors, and we identify a novel OA/TA cell type that suppresses aggression in both sexes. This resource establishes a practical and conceptual foundation for cell-type-resolved analysis of OA/TA circuit function and enables direct integration of genetics, anatomy, and connectomics for studies of neuromodulatory circuit organization.

neuroscience↗

bioRxiv2025

Electrical synapses mediate visual approach behavior

Detecting salient visual objects and orienting toward them are commonplace tasks for animals, yet the underlying neural circuits remain poorly understood. The fruit fly is an ideal model for a comprehensive analysis of feature detection mechanisms given its complete synaptic wiring diagrams, robust behavioral assays, and cell-type-specific gene expression datasets. We previously showed that columnar T3 neurons are required for saccadic orientation toward landscape features during flight. Here, we examine how signals downstream of T3 are processed in the central brain. We identify LC17 visual projection neurons as key postsynaptic targets: they receive strong excitatory input from T3, project to premotor brain regions, and are thus positioned to support visual approach. Using in vivo optical physiology and virtual reality behavior, we demonstrate that LC17 neurons are indeed necessary for object tracking during flight. Furthermore, we find that electrical synapses in LC17 are also required for tracking behavior. We show that the innexin Shaking B (shakB) is highly expressed in LC17 and localized to its dendrites, and genetic perturbations confirm its essential role for electrical coupling in this circuit. Our findings reveal mechanisms underlying visual approach, and highlight the interplay between electrical and chemical neurotransmission for rapid object detection and action selection.

neuroscience↗

bioRxiv2025

A Syntaxin1A protein mutation drives sleep reduction in Drosophila

Syntaxin1A is a key component in the regulation of the vesicle fusion nanomachine and, together with VAMP/synaptobrevin and SNAP-25, forms the core of the SNARE complex, that is the molecular nanomachine regulating neurotransmitter release. Syntaxin1A is localized on the cytosolic face of the presynaptic membrane and with Munc-18-1 is thought to be the starting point for the SNARE complex assembly.1 In flies, aspartic-to-arginine amino acid substitution at position 253 of the protein sequence reduces synaptic release by affecting the assembly of multiple SNARE complexes into a super-complex without interfering with the single complex formation per se.2 In this study, we analyzed sleep behavior in flies expressing this mutated isoform of Syntaxin1A panneuronally. According to the synaptic homeostasis hypothesis,3 the overall decrease of synaptic activity during the previous period of wakefulness should reduce the need for sleep.4 We observed a reduction in the total amount of sleep in flies expressing the mutated isoform compared to controls. Moreover, the sleep pattern of the Syntaxina1A mutant flies was more fragmented compared to controls. Video-tracking analysis of free walking flies in an open-field arena showed that these changes were not caused by higher locomotor activity during the daytime relative to controls. Our results suggest that the widespread effect of Syntaxin1A mutation on synapses may lead to a dampening of the information load among neurons and, consequently, impact the regulation of sleep at the cellular level. HighlightsO_LIThe neurotransmitter release machinery modulates sleep in Drosophila C_LIO_LIA Syntaxin1A protein mutation causes fragmented night sleep C_LIO_LIMotor activity is not affected by the Syntaxin1A mutation C_LIO_LISyntaxin1A could regulate the homeostasis of vesicle fusion and sleep C_LI In briefFrighetto et al., investigated the role of a single amino acid substitution in the Syntaxin1A protein in sleep and locomotor behavior. Following the pan-neuronal expression of this mutated Syntaxin1A, they found a specific reduction of sleep with locomotion remaining largely unaffected.

neuroscience↗

bioRxiv2024

Gradients of Recognition Molecules Shape Synaptic Specificity of a Visuomotor Transformation

Converting sensory information into motor commands is fundamental to most of our actions. In Drosophila, visuomotor transformations are mediated by Visual Projection Neurons (VPNs). These neurons convert object location and motion into directional behaviors downstream through a synaptic gradient mechanism. However, the molecular origins of such graded connectivity remain unknown. We addressed this question in a VPN cell type called LPLC2, which integrates looming motion and transforms it into an escape response through two parallel dorsoventral synaptic gradients at its inputs and outputs. We identified two corresponding dorsoventral expression gradients of cell recognition molecules within the LPLC2 population that regulate this synaptic connectivity. Dpr13 determines synaptic outputs of LPLC2 axons by interacting with its binding partner DIP-{varepsilon} expressed in the Giant Fiber, a neuron that mediates escape. Similarly, beat-VI regulates synaptic inputs onto LPLC2 dendrites by interacting with Side-II expressed in upstream motion-detecting neurons. Behavioral, physiological, and molecular experiments demonstrate that these coordinated molecular gradients control differential synaptic connectivity, enabling the accurate transformation of visual features into motor commands. As within-neuronal-type variation in gene expression is also observed in the mammalian brain, graded expression of cell recognition molecules may represent a common mechanism underlying synaptic specificity.

neuroscience↗

bioRxiv2022

Feature detecting columnar neurons mediate object tracking saccades in Drosophila

Tracking visual objects while stabilizing the visual background is complicated by the different computational requirements for object tracking and motion vision. In fruit fly, directionally selective motion detectors T4 and T5 cells supply wide-field neurons of the lobula plate, which control smooth gaze stabilization behavior. Here, we hypothesized that an anatomically parallel pathway supplied by T3, which encodes small moving objects and innervates the lobula, drives body saccades toward objects. We combined physiological and behavioral experiments to show that T3 neurons respond omnidirectionally to contrast changes induced by the visual stimuli that elicit tracking saccades, and silencing T3 reduced the frequency of tracking saccades. By contrast, optogenetic manipulation of T3 increased the number of tracking saccades. Our results represent the first evidence that parallel motion detection and feature detection pathways coordinate smooth gaze stabilization and saccadic object tracking behavior during flight.

neuroscience↗

bioRxiv2019

Searching for relief: Drosophila melanogaster navigation in a virtual bitter maze

Animals use pain-relief learning to discern which actions can diminish or abolish noxious stimuli. If relief from pain is provided in a specific location, place learning is the mechanism used to pinpoint that location in space. Little is known about how physiological and non-directly damaging stimuli can alter visual-based searching behaviour in animals. Here we show how the optogenetically-induced activation of bitter-sensing neurons urges Drosophila melanogaster to seek relief from bitter taste stimulation and that this distressful, but ecologically relevant stimulus, innately wired to the threat of intoxication, is sufficient to elicit pain-relief-like behavioural responses. Specifically, freely walking flies inside an open circular arena are trained to seek relief from the unpleasant stimulation by searching for a safe area alternatively positioned in the proximity of a pair of identical, diametrically opposed, visual markers. Moreover, and perhaps more importantly, under this paradigm flies develop visual place learning manifested by their seeking relief in the zone associated with bitter relief during the last trial of training, even when exposed to constant bitter stimulation with no relief provided. An important implication is that this form of learning does not lead to operant conditioning generalization. We further propose that kinematic indexes, such as the spatially-specific reduction of locomotor velocity, may provide immediate evidence of relief-based place learning and spatial memory.

animal behavior and cognition↗

bioRxiv2018

Mechanisms of selection for the control of action in Drosophila melanogaster

In the last few years several studies have investigated the neural mechanisms underlying spatial orientation in Drosophila melanogaster. Convergent results suggest that this mechanism is associated with specific neural circuits located within the Central Complex (CC). Furthermore such circuits appear to be associated with visual attention, specifically with selective attention processes implicated in the control of action. Our aim was to understand how wild-type flies react to the abrupt appearance of a visual distractor during an ongoing locomotor action. Thus, we adapted the well-known Buridan paradigm, used to study walking behaviour in flies, so we could specifically address the mechanisms involved in action selection. We found that flies tended to react in one of two ways when confronted with a visual distractor during ongoing locomotion. Flies either: (i) committed to a new path situated midway between the original target and the distractor, consistent with a novelty effect; or (ii) remained on the original trajectory with a slight deviation in direction of the distractor. We believe that these results provide the first indication of how flies react, from the motor point of view, in a bi-stable context requiring the presence of selection-for-action mechanisms. Some considerations on the neural circuits underlying such behavioural responses are advanced.

animal behavior and cognition↗