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bioRxiv2025

Octopamine regulates neural circuits in the mushroom body and central complex, influencing sleep and context-dependent arousal.

Sleep is a complex and ubiquitous phenomenon in the animal kingdom, yet the mechanisms, modes, and effects of sleep on the brain and body remain highly variable and not fully understood. While sleep and wakefulness are often measured as two binary states at the behavioral level, animals exhibit a wide range of arousal states during wakefulness. Behaviors such as feeding, courting, escaping predators, or avoiding unfavorable environments are critical for survival and often compete with sleep. Biogenic amines, including dopamine, norepinephrine, and serotonin, are known to regulate sleep and arousal behaviors across species, offering valuable insights into how these states are co-regulated. In this study, we leverage the small number, discrete organization, and well-defined connectivity patterns of neuromodulatory neurons in the fly brain to investigate how specific octopamine (OA) neurons regulate sleep and context-dependent arousal. We focus on a pair of OA neurons, VPM3, which project extensively to the mushroom body (MB) and central complex (CX). Our findings reveal that VPM3 neurons are sexually monomorphic and that their activity is essential for sleep suppression and male courtship behavior. Furthermore, we demonstrate that the male-specific form of the fruitless gene in these neurons plays a critical role in sleep regulation and that their activity is influenced by sleep history. Using connectome data and highly specific genetic tools, we identify upstream inputs to VPM3 neurons from the CX and elucidate the downstream pathways mediated by the MB, as well as the role of specific OA receptors. These detailed investigations highlight the multifaceted role of octopamine in sleep suppression and context-specific arousal, providing a crucial link between identified sleep microcircuits in the mushroom body and central complex.

neuroscience↗

bioRxiv2025

A comprehensive mechanosensory connectome reveals a somatotopically organized neural circuit architecture controlling stimulus-aimed grooming of the Drosophila head

Animals respond to tactile stimulations of the body with location-appropriate behavior, such as aimed grooming. These responses are mediated by mechanosensory neurons distributed across the body, whose axons project into somatotopically organized brain regions corresponding to body location. How mechanosensory neurons interface with brain circuits to transform mechanical stimulations into location-appropriate behavior is unclear. We previously described the somatotopic organization of bristle mechanosensory neurons (BMNs) around the Drosophila head that elicit a sequence of location-aimed grooming movements (Eichler et al., 2024). Here, we use a serial section electron microscopy reconstruction of a full adult fly brain to identify nearly all of BMN pre- and postsynaptic partners, uncovering circuit pathways that control head grooming. Postsynaptic partners dominate the connectome, and are both excitatory and inhibitory. We identified an excitatory cholinergic hemilineage (hemilineage 23b), a developmentally related group of neurons that elicits aimed head grooming and exhibit differential connectivity with BMNs from distinct head locations, revealing a lineage-based somatotopically organized parallel circuit architecture. Presynaptic partners provide extensive BMN presynaptic inhibition, consistent with models of sensory gain control as a mechanism of suppressing grooming movements and controlling the sequence. This work provides the first comprehensive map of a somatotopically organized connectome, and reveals how this organization could shape grooming. It also reveals the mechanosensory interface with the brain, illuminating fundamental features of mechanosensory processing, including feedforward excitation and inhibition, feedback inhibition, somatotopic circuit organization, and developmental origins.

neuroscience↗

bioRxiv2025

Empirical validation of ephaptic coupling in printed human neural circuits

Ephaptic coupling is a phenomenon describing the influence of endogenous electric fields on neuronal activity1,2. Although ephaptic coupling is deemed to contribute to computations in the brain1,3,4, the olfactory system5, the retina6,7, and to cardiac conduction8,9, and being associated with diseases like epilepsy10,11 and arrhythmia12,13, it is still poorly understood since it is notoriously difficult to investigate in vivo and in vitro. In vitro electrophysiology allows accessible and flexible experimentation, but circuits form randomly, leading to a lack of precision and reproducibility. Here, we present a method for reproducibly constructing human neuronal networks in vitro with single-cell precision. We constructed neuronal circuits from the bottom up by bringing their axons into close contact. This enabled us to measure the effects of ephaptic coupling and validate theoretical predictions, such as reduced action potential velocity, increased activity synchronization14-16 and reduced stimulation threshold17. Our precise measurements of electrophysiological activity support the importance of ephaptic coupling in neuronal circuit function. Printed neuronal circuits allow detailed in vitro studies of neuronal interactions and may serve as a platform for disease modeling related to synaptic, ephaptic, or myelination processes.

bioengineering↗

bioRxiv2025

Fentanyl and Alcohol Co-Exposure Induce Robust, Sustained Hyperlocomotion and Neural Circuit Disruption in Larval Zebrafish

The constantly evolving trends in substance abuse are a major concern for health authorities worldwide, and these trends include an increasing prevalence of poly-substance misuse. For instance, opioid overdoses are frequently accompanied by alcohol co-use, yet the combined effects of these substances remain poorly understood. Using zebrafish as a highly relevant vertebrate model of neuropharmacology, we investigated the interactions between fentanyl and alcohol, uncovering a unique and robust hyperlocomotor response characterized by initial locomotor suppression followed by persistent, erratic hyperlocomotion. Alcohol was found to be critical to this phenomenon, as substitution with other GABAA modulators failed to replicate the effect. However, the response was replicable with heroin and remifentanil, suggesting an opioid-class wide effect. In vivo whole brain imaging further demonstrated dysregulated neuronal activity, with co-administration with alcohol causing potentiated neuronal activity compared to individual drug exposures and controls. Collectively, these findings suggested an integral role of ethanol and fentanyl co-administration in dysregulated neuronal responses and reveals a complex neurobehavioral mechanism. These observations suggest further investigation is warranted into the use of the larval zebrafish model for studying the neuropharmacological interactions of multiple substances of abuse.

animal behavior and cognition↗

bioRxiv2025

HBMAP: Bayesian inference of neural circuits from DNAbarcoded projection mapping

Decoding how the brain routes information through its precise, long-range wiring remains a central challenge in neuroscience. Barcode-based mapping of axonal projections allows brain-wide, high-throughput investigation of projections at single-neuron resolution offering a powerful solution. However, principled methods for statistical analysis of barcode count data that can detect common projection rules and effectively integrate datasets across subjects are lacking. To address these issues, we developed a model-based clustering approach through hierarchical Bayesian mixtures which we call hierarchical Bayesian mapping of axonal projections (HBMAP). We show that the inferred model accurately reflects the features of the data and allows simultaneous identification of projection patterns and characterization of uncertainty that accounts for subject variability. Our study presents the first Bayesian approach to barcode-based projection mapping, offering a general solution for this class of data.

neuroscience↗

bioRxiv2025

A Neural Circuit for Modular Gating of Organ Somatosensation

End-organs such as the bladder rely on a delicate balance between internal urgency and voluntary restraint. However, the specific spinal circuits coordinating these functions remain poorly defined. Here, we identify a genetically defined population of lumbosacral spinal interneurons marked by Trpc4 expression that gate bladder sensory input and regulate micturition reflexes. Single-cell transcriptomics and in situ physiology reveal molecularly distinct Trpc4 subtypes. Functional manipulation reveals that Trpc4 neurons are essential for coordinating bladder-sphincter activity and gating visceral pain. Their ablation leads to bladder hypersensitivity and voiding dysfunction, while targeted activation reverses these maladaptive states. Circuit tracing reveals convergence of primary afferent and descending brainstem inputs onto Trpc4 neurons. These findings establish Trpc4 interneurons are critical for bladder sensory-motor integration and extend classical spinal gating models to encompass visceral pain and organ reflex control.

neuroscience↗

bioRxiv2018

Neural circuit basis of aversive odour processing in Drosophila from sensory input to descending output.

Evolution has shaped nervous systems to produce stereotyped behavioural responses to ethologically relevant stimuli. For example when laying eggs, female Drosophila avoid geosmin, an odorant produced by toxic moulds. Here we identify second, third, and fourth order neurons required for this innate olfactory aversion. Connectomics data place these neurons in a complete synaptic circuit from sensory input to descending output. We find multiple levels of valence-specific convergence, including a novel form of axo-axonic input onto second order neurons conveying another danger signal, the pheromone of parasitoid wasps. However, we also observe extensive divergence: second order geosmin neurons connect with a diverse array of 80 third order cell types. We find a pattern of convergence of aversive odour channels at this level. Crossing one more synaptic layer, we identified descending neurons critical for egg-laying aversion. Our data suggest a transition from a labelled line organisation in the periphery to a highly distributed central brain representation that is then coupled to distinct descending pathways.

neuroscience↗

bioRxiv2018

Impaired social behaviour and molecular mediators of associated neural circuits during chronic Toxoplasma gondii infection in female mice

Toxoplasma gondii (T. gondii) is a neurotropic parasite that is associated with various neuropsychiatric disorders. Rodents infected with T. gondii display a plethora of behavioural alterations, and Toxoplasma infection in humans has been strongly associated with disorders such as schizophrenia, in which impaired social behaviour is an important feature. Elucidating changes at the cellular level relevant to neuropsychiatric conditions can lead to effective therapies. Here, we compare changes in behaviour during an acute and chronic T. gondii infection in female mice. Further, we notice that during chronic phase of infection, mice display impaired sociability when exposed to a novel conspecific. Also, we show that T. gondii infected mice display impaired short-term social recognition memory. However, object recognition memory remains intact. Using c-Fos as a marker of neuronal activity, we show that infection leads to an impairment in neuronal activation in the medial prefrontal cortex, hippocampus as well as the amygdala when mice are exposed to a social environment and a change in functional connectivity between these regions. We found changes in synaptic proteins that play a role in the process of neuronal activation such as synaptophysin, PSD-95 and changes in downstream substrates of cell activity such as cyclic AMP, phospho-CREB and BDNF. Our results point towards an imbalance in neuronal activity that can lead to a wider range of neuropsychiatric problems upon T. gondii infection.

neuroscience↗

bioRxiv2018

A VTA GABAergic neural circuit mediates visually evoked innate defensive responses

Innate defensive responses are essential for animal survival and are conserved across species. The ventral tegmental area (VTA) plays important roles in learned appetitive and aversive behaviors, but whether it plays a role in mediating or modulating innate defensive responses is currently unknown. We report that GABAergic neurons in the mouse VTA (VTAGABA+) are preferentially activated compared to VTA dopaminergic (VTADA+) neurons when a threatening visual stimulus evokes innate defensive behavior. Functional manipulation of these neurons showed that activation of VTAGABA+ neurons is indispensable for looming-evoked defensive flight behavior and photoactivation of these neurons is sufficient for looming-evoked defensive-like flight behavior, whereas no such role can be attributed for VTADA+ neurons. Viral tracing and in vivo and in vitro electrophysiological recordings showed that VTAGABA+ neurons receive direct excitatory inputs from the superior colliculus (SC). Furthermore, we showed that glutamatergic SC-VTA projections synapse onto VTAGABA+ neurons that project to the central nucleus of the amygdala (CeA) and that the CeA is involved in mediating the defensive behavior. Our findings demonstrate that visual information about aerial threats access to the VTAGABA+ neurons mediating innate behavioral responses, suggesting a more general role for the VTA.

neuroscience↗

bioRxiv2019

Cre-assisted Fine-mapping of Neural Circuits using Orthogonal Split Inteins

Summary:Genetic methods for targeting small numbers of neurons of a specific type are critical for mapping the brain circuits underlying behavior. Existing methods can provide exquisite targeting precision in favorable cases, but for many cases alternative techniques will be required. Here, we introduce a new step-wise combinatorial method for sequentially refining neuronal targeting: Depending on the restriction achieved at the first step, a second step can be easily implemented to further refine expression. For both steps, the new method relies on two independent intersections. The primary intersection targets neurons based on their developmental origins (i.e. lineage) and terminal identities, while the second intersection limits the number of lineages represented in the primary intersection by selecting lineages with overlapping activity of two distinct enhancers during neurogenesis. Our method relies critically on two libraries of 134 transgenic fly lines that express fragments of a split Cre recombinase under the control of distinct neuroblast enhancers. The split Cre fragments are fused to non-interacting pairs of split inteins, which ensure reconstitution of full-length and active Cre when all fragments are expressed in the same cell. Our split Cre system, together with its open source libraries, represent off-the-shelf components that should facilitate the targeting and characterization of brain circuits in Drosophila. Our methodology may also prove useful in other genetic model organisms.

neuroscience↗

bioRxiv2019

Cellular and synaptic adaptations of neural circuits processing skylight polarization in the fly

Specialized ommatidia harboring polarization-sensitive photoreceptors exist in the dorsal rim area (DRA) of virtually all insects. Although downstream elements have been described both anatomically and physiologically throughout the optic lobes and the central brain of different species, little is known about their cellular and synaptic adaptations and how these shape their functional role in polarization vision. We have previously shown that in the DRA of Drosophila melanogaster, two distinct types of modality-specific distal medulla cell types (Dm-DRA1 and Dm-DRA2) are post-synaptic to long visual fiber photoreceptors R7 and R8, respectively. Here we describe additional neuronal elements in the medulla neuropil that manifest modality-specific differences in the DRA region, including DRA-specific neuronal morphology, as well as differences in the structure of pre- or post-synaptic membranes. Furthermore, we show that certain cell types (medulla tangential cells and octopaminergic neuromodulatory cells) specifically avoid contacts with polarization-sensitive photoreceptors. Finally, while certain transmedullary cells are specifically absent from DRA medulla columns, other subtypes show specific wiring differences while still connecting the DRA to the lobula complex, as previously been described in larger insects. This hints towards a complex circuit architecture with more than one pathway connecting polarization-sensitive DRA photoreceptors with the central brain.

neuroscience↗

bioRxiv2026

A state-dependent neural circuit resolves approach-avoidance conflicts

To survive, animals must balance opportunity and risk, yet how internal motivational state biases this trade-off remains poorly understood. Here we show that hunger gates nociceptive avoidance in Drosophila to enable food approach under conflict. Using a behavioural assay in which flies must cross an electric shock barrier to reach food, we find that starvation promotes shock tolerance only when food-related olfactory cues are present. This state- and context-dependent behavioural shift is mediated by a defined neuromodulatory circuit. Leucokinin neurons encode hunger and convey this information to PV5K1 lateral horn output neurons, which integrate internal state signals with food odour cues and suppress shock-responsive FB2B neurons in the ventral fan-shaped body. Accordingly, electric shock-evoked activity in FB2B neurons is suppressed in starved flies exposed to food cues. These findings identify a circuit mechanism by which motivational state gates aversive processing to bias action selection towards goal-directed behaviour. TeaserHunger enables flies to suppress nociceptive avoidance when food cues signal reward availability via a defined neuromodulatory circuit.

neuroscience↗

bioRxiv2026

Transsynaptic neural circuit mapping of ventral hippocampus motivational control systems

The ventral hippocampus contributes to food intake regulation and a range of motivational and memory processes, and its dysfunction is associated with several cognitive and behavioral disorders. However, its circuit-level organization remains incompletely understood. Ventral CA1 (CA1v) neurons send projections to several regions involved in motivational control. Here we focus on three major forebrain targets: the nucleus accumbens shell (ACBsh), medial prefrontal cortex (mPFC), and lateral hypothalamic area (LHA). We mapped the upstream and downstream circuitry of CA1v neurons defined by their projections to these target regions in rats using complementary transsynaptic anterograde and retrograde viral tracing approaches. Monosynaptic outputs to ACBsh, mPFC, and LHA were targeted using ATLAS, a novel transsynaptic anterograde viral approach that drives Cre recombinase in neurons receiving glutamatergic synaptic transmission from the CA1v. Second-order projections arising from these defined pathways were then mapped using a Cre-dependent anterograde viral tracing strategy. In parallel, upstream inputs to CA1v neurons projecting to each downstream target were mapped using a conditional retrograde glycoprotein-deleted rabies viral approach. Anterograde tracing revealed both shared and pathway-specific second-order targets, including bidirectional CA1v projections. Retrograde tracing confirmed expected inputs (e.g., CA3) and uncovered previously unrecognized cortical sources that differed across downstream projection-defined CA1v subpopulations. Together, these findings delineate pathway-specific, multinode circuits linking CA1v neurons to key motivational systems that may inform future therapeutic strategies for disorders involving ventral hippocampal dysfunction.

neuroscience↗

bioRxiv2026

Identification of a neural circuit that enables safe, long-term torpor in mice

Torpor, a state of regulated hypothermia and hypometabolism, is a critical survival strategy in certain mammals. Previous studies established the primacy of neuron control in initiating acute torpor. However, whether neuromodulation can safely sustain torpor over the long term, and the specific governing pathways, remain unanswered challenges limiting its translational potential. Here we identify a distinct preoptic neuronal population expressing General control nonderepressible 2 ( G neurons) in mice that is essential and sufficient for torpor induction. Strikingly, sustained and selective activation of G neurons induces a stable, weeks-long torpid state (G neuron-driven long-term torpor, GLT), from which animals arouse without obvious behavioral deficits or tissue pathology. In contrast, long-term torpor driven by pan-neuronal activation of the same brain region (PLT) causes multiple post-recovery damages, underscoring the unique safety profile of selective pathway of G neurons. In a mouse cancer model, GLT directly suppressed tumor proliferation and markedly sensitized tumors to chemotherapy, achieving profound therapeutic outcomes. Together, we delineate a distinct neuronal population safely enabling prolonged torpor. This establishes a specific paradigm for inducing a stable and sustained hypometabolic state, providing a transformative platform for fundamental physiological research and pioneering clinical strategies against chronic pathologies such as cancer.

neuroscience↗

bioRxiv2026

Mapping Enteric Neural Circuits by Anterograde Transsynaptic Tracing

The diverse functions of the enteric nervous system (ENS) arise from communication between molecularly distinct neuronal populations organized into complete circuits. While recent single-cell transcriptomic studies have resolved the molecular identity of enteric neuron classes, methods for defining their synaptic connectivity remain limited. Here, we describe the implementation of mWmC, an anterograde monosynaptic tracer based on a fusion of wheat germ agglutinin (WGA) and mCherry, as a non-toxic, single-component viral tool for mapping neuronal circuits within and beyond the ENS. Following adeno-associated virus (AAV)-mediated expression in enteric neurons, mWmC was efficiently expressed and transmitted selectively to postsynaptic neurons, with no detectable transfer to enteric glia, interstitial cells of Cajal, blood vessels or other mesenchymal cell types. The method also identified postsynaptic neurons in the celiac-superior mesenteric ganglia following tracing of intestinofugal enteric neurons, demonstrating its utility for mapping inter-organ circuits. As proof of principle, we applied mWmC to two genetically defined myenteric interneuron populations and identified preferential postsynaptic targets, revealing selective connectivity with distinct enteric neuron classes. Time-course experiments showed that transsynaptic labeling occurred between 4 and 10 days and reached a plateau thereafter, consistent with monosynaptic transfer. Finally, we developed a dual-reporter version of the system that simultaneously distinguishes input and target neurons within the same tissue. Together, mWmC provides a robust approach for defining circuit architecture in the ENS, linking molecular cell atlases with neuronal connectivity and paving the way for deeper insights into the circuit mechanisms underlying gut physiology. Graphical AbstractSchematics illustrating the implementation and applications of the anterograde monosynaptic tracer mWmC for mapping enteric neuronal circuits. Parts of schematics are generated with Biorender. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=36 SRC="FIGDIR/small/741165v2_ufig1.gif" ALT="Figure 1"> View larger version (12K): org.highwire.dtl.DTLVardef@19635bborg.highwire.dtl.DTLVardef@a18ffborg.highwire.dtl.DTLVardef@f3d011org.highwire.dtl.DTLVardef@e1359c_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

A male-specific neural circuit for appetitive thirst in Drosophila

Thirst is the brain representation of the need to restore water balance. While environmental and interoceptive sensory neurons that assess water availability and status are known, the central brain representation of thirst that determines behavior in Drosophila is less well understood. We identified a male-specific appetitive thirst circuit in Drosophila using circuit mapping, connectomics, and behavior measurements. Male-specific NPF-M neurons receive thirsty seeking information via Allatostatin A (AstA) neuropeptide released from the Janu-AstA projection neuron. In turn, NPF-M neurons release the neuropeptides sNPF, NPF, and DH31 to promote thirsty water seeking and the neurotransmitter acetylcholine to inhibit it. NPF-M neurons regulate multiple motivated behaviors, including appetitive and consummatory thirst, food foraging, and courtship, driven by distinct input neurons. NPF-M neurons output to appetitive and aversive dopaminergic, mushroom body ongoing behavior integration center, and navigation circuits. This circuit exhibits similarities to those for hungry food foraging and courtship. NPF-M and Janu-AstA form a network with OviIN hub neurons that are sex-independent thirst neurons. We suggest that NPF-M neurons form a circuit branch that funnels male-specific information to tune motivated behavior.

neuroscience↗

bioRxiv2024

Artificial Embodied Circuits Uncover Neural Architectures of Vertebrate Visuomotor Behaviors

All brains evolve within specific sensory and physical environments1. Traditionally, neuroscience has focused on studying neural circuits in isolation, yet holistic characterization of their function requires integrative brain-body testing2,3. To investigate the neural and biomechanical mechanisms of sensorimotor transformations, we constructed realistic neuromechanical simulations (simZFish) of the larval zebrafish optomotor response, a visual stabilization behavior4,5. By computationally reproducing the body, physical body-water interactions, visual environments, and experimentally derived neural architectures, we closely replicated the behavior of real zebrafish6. Through systematic manipulation of physiological and circuit features, impossible in biological experiments, we demonstrate how embodiment shapes neural circuit architecture and behavior. When challenged with novel visual stimuli, simZFish predicted neuronal response types, which we identified via calcium imaging in the brain of real zebrafish and used to update the simZFish neural network. In virtual rivers, simZFish performed rheotaxis by using current-induced optic flow as navigational cues, compensating for the simulated water flow. Finally, a physical robot (ZBot) validated the role of embodied sensorimotor circuits in maintaining position in a real river with complex fluid dynamics and visual environments. Together, by iterating between simulations, behavioral observations, neural imaging, and robotic testing, we demonstrate the power of an integrative approach to investigating sensorimotor processing. Research HighlightsO_LIDeveloped simZFish, an open-source neuromechanical simulation modeling the zebrafish optomotor response (OMR). C_LIO_LIDemonstrated that simZFish visuomotor neural circuits are sufficient to maintain position in virtual water currents without additional sensory modalities. C_LIO_LIInvestigated how variations in eye geometry influence neural circuit functionality and behavior. C_LIO_LIConducted optic flow analysis of simulated visual input to identify retinal connectivity requirements, uncovering the factors that shape pretectal neurons preference for the lower posterior visual field. C_LIO_LIsimZFish predicted new neural response types confirmed via real zebrafish calcium imaging. C_LIO_LIValidated simZFish circuits with a physical robot, ZBot, performing rheotaxis in a natural river with rich visual and complex flow dynamics compared to idealized lab and simulation experiments. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/629427v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@11f2acforg.highwire.dtl.DTLVardef@133b1f3org.highwire.dtl.DTLVardef@e808bcorg.highwire.dtl.DTLVardef@1959616_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical abstractCombining data-driven neuromechanical simulations and robotic testing, we established an integrative framework for investigating embodied neural circuit functions. Leveraging the behavioral, neurobiological, and theoretical foundations of the visually guided optomotor response in larval zebrafish (blue, left), we developed a virtual zebrafish, simZFish (red, middle), to replicate realistic hydrodynamic, anatomical, sensory, neural, and behavioral aspects, permitting the investigation of emergent properties driven by embodiment. Validating these findings using a physical, zebrafish-inspired robot, ZBot (grey, right), in naturalistic environments informs further experiments, hypotheses, and robotic design.

neuroscience↗

bioRxiv2024

Adult expression of the cell adhesion protein Fasciclin 3 is required for the maintenance of adult olfactory interneurons

The proper functioning of the nervous system is dependent on the establishment and maintenance of intricate networks of neurons that form functional neural circuits. Once neural circuits are assembled during development, a distinct set of molecular programs is likely required to maintain their connectivity throughout the lifetime of the organism. Here, we demonstrate that Fasciclin 3 (Fas3), an axon guidance cell adhesion protein, is necessary for the maintenance of the olfactory circuit in adult Drosophila. We utilized the TARGET system to spatiotemporally knockdown Fas3 in selected populations of adult neurons. Our findings show that Fas3 knockdown results in the death of olfactory circuit neurons and reduced survival of adults. We also demonstrated that Fas3 knockdown activates caspase-3 mediated cell death in olfactory local interneurons, which can be rescued by overexpressing p35, an anti-apoptotic protein. This work adds to the growing set of evidence indicating a critical role for axon guidance proteins in the maintenance of neuronal circuits in adults. SUMMARY STATEMENTLittle is known about the maintenance of adult neural circuits. We show that the continuous expression of Fasciclin 3, a cell adhesion protein involved in axon guidance, is required for neuronal survival in the adult olfactory circuit.

neuroscience↗