Peter Soba

Animals rely on light not only for vision but also to adapt behavior to their environment through non-image-forming pathways. In Drosophila, most rhodopsins mediate retinal image formation, but RHODOPSIN 7 (RH7) is widely expressed in the brain and optic lobe, acting as a non-canonical light sensor reminiscent of mammalian melanopsin. We combined expression mapping, behavioral assays, and phylogenetic comparisons to investigate its function. RH7 detects temporal changes in luminance, guiding rapid behavioral responses, and regulating daily activity patterns. Flies lacking RH7 are less active during the dark phase, while strains with constitutively active RH7 show increased activity. Phylogenetic analyses suggest that RH7 is an ancient rhodopsin present across panarthropods, representing an intermediate between G protein-coupled receptors and specialized rhodopsins, highlighting a key step in the evolution of non-visual light perception. These findings show that RH7 functions as a melanopsin-like sensor, shaping behavior, and illuminating the origins of light detection.

Animals rely on light not only for vision but also to adapt behavior to their environment. In Drosophila, most rhodopsins mediate retinal image formation, but RHODOPSIN 7 (RH7) is widely expressed in the brain and optic lobe, acting as a non-retinal light sensor reminiscent of mammalian melanopsin. We combined expression mapping, behavioral assays, and phylogenetic comparisons to investigate its function. RH7 detects light-on and light-off transitions, modulates contrast, motion, and brightness perception, and contributes to circadian clock synchronization. Flies lacking RH7 are less active during the dark phase, while strains with constitutively active protein show increased activity. Phylogenetic analyses suggest that RH7 is an ancient rhodopsin present across panarthropods, representing an intermediate between G protein-coupled receptors and specialized rhodopsins, highlighting a key step in the evolution of non-visual light perception. These findings show that RH7 functions as a melanopsin-like sensor, shaping behavior and illuminating the origins of light detection.

1 Animals rely on light not only for vision but also to adapt behavior to their environment. In Drosophila , most rhodopsins mediate retinal image formation, but RHODOPSIN 7 ( RH7) is widely expressed in the brain and optic lobe, acting as a non-retinal light sensor reminiscent of mammalian melanopsin. We combined expression mapping, behavioral assays, and phylogenetic comparisons to investigate its function. RH7 detects light-on and light-off transitions, modulates contrast, motion, and brightness perception, and contributes to circadian clock synchronization. Flies lacking RH7 are less active during the dark phase, while strains with constitutively active protein show increased activity. Phylogenetic analyses suggest that RH7 is an ancient rhodopsin present across panarthropods, representing an intermediate between G protein-coupled receptors and specialized rhodopsins, highlighting a key step in the evolution of non-visual light perception. These findings show that RH7 functions as a melanopsin-like sensor, shaping behavior and illuminating the origins of light detection.

Animals make economically beneficial behavioral decisions by integrating the external sensory environment with their internal state. The metabolic state, i.e. hunger, can shift priorities, prompting risk-taking and reducing responses to danger during foraging activities. How behavioral changes are processed in the nervous system to generate flexible responses based on needs and risks remains largely unclear. Here, we demonstrate in Drosophila larvae that the corticotropin releasing hormone (CRH) homolog diuretic hormone 44 (Dh44) and its producing neurons exert metabolic top-down control of behavioral choice in a conflicting sensory context. The metabolic state via Dh44 signaling mediates the transition from avoiding to tolerating aversive light conditions in the presence of food. In vivo imaging of neuropeptide release revealed that Dh44 regulates the acute release Insulin-like peptide 7 (Ilp7) specifically in a conflicting context, thereby inducing light tolerance. Optogenetic activation of specific subsets of Dh44 or Ilp7 producing neurons during starvation is sufficient to shift behavior from light tolerance to avoidance by regulating light avoidance circuit responses. This top-down feedforward peptidergic circuit may represent a general mechanism that helps organisms to balance risk-taking with metabolic needs by allowing flexible adjustment of behavior in a conflicting multisensory environment.

Animals make economically beneficial behavioral decisions by integrating the external sensory environment with their internal state. The metabolic state, i.e. hunger, can shift priorities, prompting risk-taking and reducing responses to danger during foraging activities. How behavioral changes are processed in the nervous system to generate flexible responses based on needs and risks remains largely unclear. Here, we demonstrate in Drosophila larvae that the corticotropin releasing hormone (CRH) homolog diuretic hormone 44 (Dh44) and its producing neurons exert metabolic top-down control of behavioral choice in a conflicting sensory context. The metabolic state via Dh44 signaling mediates the transition from avoiding to tolerating aversive light conditions in the presence of food. In vivo imaging of neuropeptide release revealed that Dh44 regulates the acute release of Insulin-like peptide 7 (Ilp7) specifically in a conflicting context, thereby inducing light tolerance. Optogenetic activation of specific subsets of Dh44 or Ilp7 producing neurons during starvation is sufficient to shift behavior from light tolerance to avoidance by regulating light avoidance circuit responses. This top-down feedforward peptidergic circuit may represent a general mechanism that helps organisms to balance risk-taking with metabolic needs by allowing flexible adjustment of behavior in a conflicting multisensory environment.

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.

To ensure their survival, animals must be able to respond adaptively to threats within their environment. However, the precise neural circuit mechanisms that underlie such flexible defensive behaviors remain poorly understood. Using neuronal manipulations, machine-learning-based behavioral detection, Electron Microscopy (EM) connectomics and calcium imaging in Drosophila larva, we have mapped the second-order interneurons differentially involved in the competition between different defensive actions and the main pathways to the motor side putatively involved in inhibiting startle-type behaviors and promoting escape behaviors in a context dependent manner. We found that mechanosensory stimulation modulates the nociceptive escape sequences and inhibits C-shape bends and Rolls in favor of startle-like behaviors. This suggests a competition between mechanosensory-induced startle responses and escape behaviors. Structural and functional connectivity revealed that the second order interneurons receive their main input from projection neurons that integrate mechanosensory and nociceptive stimuli. The analysis of their postsynaptic connectivity in EM revealed that they make indirect connections to the pre-motor and motor neurons. Finally, we identify a pair of descending neurons that could promote modulate the escape sequence and promote startle behaviors. Altogether, these results characterize the pathways involved in the Startle and Escape competition, modulated by the sensory context.

Neuromodulatory signaling via G protein-coupled receptors (GPCRs) plays a pivotal role in regulating neural network function and animal behavior. The recent development of optogenetic tools to induce G protein-mediated signaling provides the promise of acute and cell type-specific manipulation of neuromodulatory signals. However, designing and deploying optogenetically functionalized GPCRs (optoXRs) with accurate specificity and activity to mimic endogenous signaling in vivo remains challenging. Here we optimize the design of optoXRs by considering evolutionary conserved GPCR-G protein interactions and demonstrate the feasibility of this approach using two Drosophila Dopamine receptors (optoDopRs). These optoDopRs exhibit high signaling specificity and light sensitivity in vitro. In vivo, we show receptor and cell type-specific effects of dopaminergic signaling in various behaviors, including the ability of optoDopRs to rescue the loss of the endogenous receptors. This work demonstrates that optoXRs can enable optical control of neuromodulatory receptor-specific signaling in functional and behavioral studies.

Dendrites are specialized neuronal compartments that sense, integrate and transfer information in the neural network. Their development is tightly controlled and abnormal dendrite morphogenesis is strongly linked to neurological disorders. While dendritic morphology ranges from relatively simple to extremely complex for a specified neuron, either requires a functional secretory pathway to continually replenish proteins and lipids to meet dendritic growth demands. The Golgi apparatus occupies the center of the secretory pathway and is regulating posttranslational modifications, sorting, transport, and signal transduction, as well as acting as a non-centrosomal microtubule organization center. The neuronal Golgi apparatus shares common features with Golgi in other eukaryotic cell types but also forms distinct structures known as Golgi outposts that specifically localize in dendrites. However, the organization and function of Golgi in dendrite development and its impact on neurological disorders is just emerging and so far lacks a systematic summary. We describe the organization of the Golgi apparatus in neurons, review the current understanding of Golgi function in dendritic morphogenesis, and discuss the current challenges and future directions.

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein coupled receptor (GPCRs) pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision, or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin ( Pd CO) is an efficient, versatile, light-activated bistable GPCR that can suppress synaptic transmission in mammalian neurons with high temporal precision in-vivo . Pd CO has superior biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that Pd CO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.