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Results for “neural circuits”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2025

Axially decoupled photo-stimulation and two photon readout (ADePT) for mapping functional connectivity of neural circuits

All-optical in vivo physiology enables three-dimensional interrogation of neural circuits function. Here, we introduce ADePT (Axially-Decoupled Photo-stimulation and Two-photon readout), a strategy that combines flexible optogenetic stimulation with neural activity imaging. ADePT achieves axially contained widefield patterned stimulation by coupling a digital micro-mirror device illuminated by a solid-state laser to a motorized holographic diffuser, while in parallel performing multiphoton imaging across different z-planes. As a proof of principle, we apply ADePT to map excitatory and inhibitory functional connectivity in the mouse early olfactory system. By controlling activity in individual glomeruli on the olfactory bulb surface and recording responses from output mitral and tufted cells in deeper layers, we identify cohorts of sister cells driven by the same parent glomerulus and analyze their distinct connectivity patterns. We further report specificity in the inhibitory circuitry, as we find that GABAergic/dopaminergic (DAT+) interneurons associated with different glomeruli selectively suppress baseline and odor-evoked activity in distinct mitral and tufted cell populations. Together, these results establish ADePT as a platform for high-throughput functional connectivity mapping in optically accessible brain regions.

neuroscience↗

bioRxiv2024

Molecular and Neural Circuit Mechanisms Underlying Sexual Experience-dependent Long-Term Memory in Drosophila.

The neural and molecular underpinnings of sexual experience-dependent long-term memory (SELTM) in male Drosophila melanogaster remain poorly understood, despite its significance for reproductive success. Here, we dissect the role of a specific class of neurons, termed Yuelao (YL) neurons, in the formation of SELTM and the associated molecular pathways. We employed a combination of genetic manipulations, immunohistochemistry, and behavioral assays in Drosophila to investigate the function of YL neurons and their molecular interactors in SELTM. Utilizing the RNA sequencing data and transgenic tools, we delineated the neural circuits involved in taste and pheromone processing relevant to SELTM. Our findings reveal that the YL neurons, expressing the Orb2 scaffolding protein, are indispensable for the formation of SELTM following sexual experience. These neurons are regulated by the neuromodulator short neuropeptide F (sNPF) and its receptor (sNPF-R), which modulate glutamate release via NMDAR2. We demonstrate that sexual experience triggers synaptic plasticity in YL neurons, characterized by an increase in dendritic and presynaptic terminal areas, and a decrease in intracellular calcium levels. Furthermore, we show that YL neurons are specialized for the generation of appetitive sexual experience-dependent memory and project to brain regions implicated in memory formation. Our study uncovers the YL neurons as a key neural substrate for SELTM in Drosophila, shedding light on the molecular and circuit mechanisms that mediate the formation of long-term memories following sexual experience. These findings provide novel insights into the neural basis of taste-related memory and have broader implications for understanding the interplay between experience, memory formation, and behavior.

neuroscience↗

bioRxiv2023

Light-Guided Rabies Virus Tracing for Neural Circuit Analysis

Neuronal tracing methods are essential tools to understand the fundamental architecture of neural circuits and their connection to the overall functional behavior of the brain. Viral vectors used to map these transsynaptic connections are capable of cell-type-specific and directional-specific labeling of the neuronal connections. Herein, we describe a novel approach to guide the transsynaptic spreading of the Rabies Virus (RV) retrograde tracer using light. We built a Baculovirus (BV) as a helper virus to deliver all the functional components necessary and sufficient for a nontoxic RV to spread from neuron to neuron, with a light-actuated gene switch to control the RV polymerase, the L gene. This design should allow for precisely controlled polysynaptic viral tracing with minimal viral toxicity. To use this system in a highly scalable and automated manner, we built optoelectronics for controlling this system in vitro with a large field of view using an off-the-shelf CMOS sensor, OLED display panel, and microcontrollers. We describe the assembly of these genetic circuits using the uLoop DNA assembly method and a library of genetic parts designed for the uLoop system. Combining these tools provides a framework for increasing the capabilities of nontoxic tracing through multiple synapses and increasing the throughput of neural tracing using viruses.

neuroscience↗

bioRxiv2019

Attractor-state itinerancy in neural circuits with synaptic depression

Neural populations with strong excitatory recurrent connections can support bistable states in their mean firing rates. Multiple fixed points in a network of such bistable units can be used to model memory retrieval and pattern separation. The stability of fixed points may change on a slower timescale than that of the dynamics due to short-term synaptic depression, leading to transitions between quasi-stable point attractor states in a sequence that depends on the history of stimuli. To better understand these behaviors, we study a minimal model, which characterizes multiple fixed points and transitions between them in response to stimuli with diverse time- and amplitude-dependences. The interplay between the fast dynamics of firing rate and synaptic responses and the slower timescale of synaptic depression makes the neural activity sensitive to the amplitude and duration of square-pulse stimuli in a non-trivial, history-dependent manner. Weak cross-couplings further deform the basins of attraction for different fixed points into intricate shapes. Our analysis provides a natural explanation for the systems rich responses to stimuli of different durations and amplitudes while demonstrating the encoding capability of bistable neural populations for dynamical features of incoming stimuli.

neuroscience↗

bioRxiv2026

A Neurotomographic Approach for Mesoscale Mapping of Neural Circuits

BackgroundBrain regions integrate neural information arriving from several convergent projection sources. At the mesoscale level, neural projections can potentially span both hemispheres and extend along the entire rostrocaudal axis, which complicates efforts to map their full extent. To address this issue, we describe a novel method for mapping such mesoscale connectivity in vivo and ex vivo. Our neurotomographic approach utilizes micro-computed tomography (micro-CT) to image the spatial distribution of neural tracers bound to high Z-elements, e.g, gold. MethodsIn this study, we conjugated colloidal gold to a retrograde tracer wheat-germ agglutinin apo-horseradish peroxidase (WGA-HRP) and then stereotactically injected the gold-bound tracer (WAHG) into the mouse forebrain. Micro-CT was then used to image the brain in vivo and ex vivo, followed by three-dimensional reconstruction of tracer distribution. We then validated our approach by histologically processing the brains using silver enhancement to label gold particles; this enabled a direct comparison of histological labeling with the neurotomographic images. ResultsWe found that micro-CT imaging could reveal the major spatial distributions of the gold-bound tracer, which was consistent across in vivo and ex vivo imaging conditions. Moreover, the neurotomographically determined patterns corresponded with the labeling observed in histologically processed tissue, with the major sites of labeling reliably detected in reconstructed neurotomographic images. ConclusionsOverall, our findings demonstrate a potential novel method for non-destructive, three-dimensional mapping of neural tracers in vivo. This novel approach can potentially guide targeted multi-site recordings, enable validation of injection site placement, and facilitate rapid longitudinal connectomic analyses in vivo.

neuroscience↗

bioRxiv2026

Design Tradeoffs in High Resolution, Large Field-of-View 3D All-Optical Control of Neural Circuits

Multiphoton holographic optogenetics is an emerging technology that offers the ability to probe neural circuits with unprecedented temporal and spatial precision. When combined with in vivo imaging, it enables a host of experiments that were not previously possible. While this approach grows in popularity, the one-size-fits-all approach of most microscopes leads to systems that are not optimized for many experimental paradigms. Focusing on scanless temporally focused holographic optogenetic approaches, we explore the tradeoffs between resolution and field of view in different microscope designs. We show that simple changes in optical elements and lens order can create systems with both improved accessible range and resolution. Taking advantage of newer, high NA, 2P-optimized, low-magnification objectives, we demonstrate cellular-resolution holographic control over neurons separated by more than 1.4 mm in a single hologram, significantly expanding the spatial extent accessible for simultaneous neural manipulation in a conventional microscope. These changes are built upon a simple framework that leverages head-to-head system comparisons as a critical approach for evaluating the true advantages and limitations of an optical design, which could be incorporated into a wide variety of microscopes.

neuroscience↗

bioRxiv2018

Connect-seq to superimpose molecular on anatomical neural circuit maps

The mouse brain contains ~100 million neurons interconnected in a vast array of neural circuits. The identities and functions of individual neuronal components of most circuits are undefined. Here we describe a method, termed Connect-seq, which combines retrograde viral tracing and single cell transcriptomics to uncover the molecular identities of upstream neurons in a specific circuit and the signaling molecules they use to communicate. Connect-seq can generate a molecular map that can be superimposed on a neuroanatomical map to permit molecular and genetic interrogation of how the neuronal components of a circuit control its function. Application of this method to hypothalamic neurons controlling physiological responses to fear and stress reveal subsets of upstream neurons that express diverse constellations of signaling molecules and can be distinguished by their anatomical locations.

neuroscience↗

bioRxiv2021

A locomotor neural circuit persists and functions similarly in larvae and adult Drosophila

Individual neurons can undergo drastic structural changes, known as neuronal remodeling or structural plasticity. One example of this is in response to hormones, such as during puberty in mammals or metamorphosis in insects. However, in each of these examples it remains unclear whether the remodeled neuron resumes prior patterns of connectivity, and if so, whether the persistent circuits drive similar behaviors. Here, we utilize a well-characterized neural circuit in the Drosophila larva: the Moonwalking Descending Neuron (MDN) circuit. We previously showed that larval MDN induces backward crawling, and synapses onto the Pair1 interneuron to inhibit forward crawling (Carreira-Rosario et al., 2018). MDN is remodeled during metamorphosis and regulates backward walking in the adult fly. We investigated whether Pair1 is remodeled during metamorphosis and functions within the MDN circuit during adulthood. We assayed morphology and molecular markers to demonstrate that Pair1 is remodeled during metamorphosis and persists in the adult fly. In the adult, optogenetic activation of Pair1 resulted in arrest of forward locomotion, similar to what is observed in larvae. MDN and Pair1 are also synaptic partners in the adult, showing that the MDN-Pair1 interneuron circuit is retained in the adult following hormone-driven pupal remodeling. Thus, the MDN-Pair1 neurons are an interneuronal circuit - i.e. a pair of synaptically connected interneurons - that persists through metamorphosis, taking on new input/output neurons, yet generating similar locomotor behavior at both stages.

neuroscience↗

bioRxiv2021

Sub-second multi-channel magnetic control of select neural circuits in behaving flies

Precisely timed activation of genetically targeted cells is a powerful tool for studying neural circuits and controlling cell-based therapies. Magnetic control of cell activity or "magnetogenetics" using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and studies of freely behaving animals. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents the precise temporal modulation of neural activity similar to light-based optogenetics. Moreover, magnetogenetics has not provided a means to selectively activate multiple channels to drive behavior. Here we produce sub-second behavioral responses in Drosophila melanogaster by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A). Furthermore, by tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we can achieve sub-second, multichannel stimulation, analogous to multi-color optogenetic stimulation. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation only possible by magnetic control.

bioengineering↗

bioRxiv2023

Ancestral neural circuits potentiate the origin of a female sexual behavior

Courtship interactions are remarkably diverse in form and complexity among species. How neural circuits evolve to encode new behaviors that are functionally integrated into these dynamic social interactions is unknown. Here we report a recently originated female sexual behavior in the island endemic Drosophila species D. santomea, where females signal receptivity to male courtship songs by spreading their wings, which in turn promotes prolonged songs in courting males. Copulation success depends on this female signal and correlates with males ability to adjust his singing in such a social feedback loop. Functional comparison of sexual circuitry across species suggests that a pair of descending neurons, which integrates male song stimuli and female internal state to control a conserved female abdominal behavior, drives wing spreading in D. santomea. This co-option occurred through the refinement of a pre-existing, plastic circuit that can be optogenetically activated in an outgroup species. Combined, our results show that the ancestral potential of a socially-tuned key circuit node to engage the wing motor program facilitates the expression of a new female behavior in appropriate sensory and motivational contexts. More broadly, our work provides insights into the evolution of social behaviors, particularly female behaviors, and the underlying neural mechanisms.

evolutionary biology↗

bioRxiv2024

Divergent Visuomotor Strategies in Teleosts: Neural Circuit Mechanisms in Zebrafish and Danionella cerebrum

Many animals respond to sensory cues with species-specific coordinated movements to successfully navigate their environment. However, the neural mechanisms that support diverse sensorimotor transformations across species with distinct navigational strategies remain largely unexplored. By comparing related teleost species, zebrafish (Danio rerio, ZF) and Danionella cerebrum (DC), we investigated behavioral patterns and neural architectures during the visually guided optomotor response (OMR). Closed-loop behavioral tracking during visual stimulation revealed that larval ZF employ burst-and-glide locomotion, while larval DC display continuous, smooth swimming punctuated with sharp directional turns. Although DC achieve higher average speeds, they lack the direction-dependent velocity modulation observed in ZF. Whole-brain two-photon calcium imaging and tail tracking in head-fixed fish reveals that both species exhibit direction-selective motion encoding in homologous regions, including the retinorecipient pretectum, with DC exhibiting fewer binocular, direction-selective neurons overall. Kinematic analysis of head-fixed behavior reveals that DC sustain significantly longer directed swim events across all stimuli than ZF, highlighting the divergent visuomotor strategies, with ZF reducing tail movement duration in response to oblique, turn-inducing stimuli. Lateralized motor-associated neural activity in the medial and anterior hindbrain of both species suggests a shared circuit motif, with distinct neural circuits that independently control movement vigor and direction. These findings highlight the diversity in visuomotor strategies among teleost species, underscored by shared sensorimotor neural circuit motifs, and establish a robust framework for unraveling the neural mechanisms driving continuous and discrete visually guided locomotion, paving the way for deeper insights into vertebrate sensorimotor functions. Research HighlightsO_LILarval DC exhibit faster swimming than ZF, matching the direction of visual motion. C_LIO_LIDC execute OMR in smooth, curved swimming patterns, interspersed with sharp directional turns. C_LIO_LIZF and DC share similar visuomotor neural architecture, recruiting pretectal and hindbrain regions. C_LIO_LIZF and DC demonstrate lateralized encoding of turns, particularly in medial hindbrain neurons. C_LI In BriefLarval Danionella cerebrum respond to global visual motion cues in smooth, low-angle swimming patterns, interspersed with sharp directional turns, swimming consistently faster than zebrafish. Fouke et al. use behavioral tracking of freely moving and head fixed fish to reveal an evolutionarily conserved visuomotor neural architecture transforming visual motion cues into species-specific locomotor behaviors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/624938v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@13076f4org.highwire.dtl.DTLVardef@d18dc8org.highwire.dtl.DTLVardef@1b35025org.highwire.dtl.DTLVardef@152d2f0_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

neuroscience↗

bioRxiv2024

Using DeepLabCut-Live to probe state dependent neural circuits of behavior with closed-loop optogenetic stimulation

BackgroundClosed-loop behavior paradigms enable us to dissect the state-dependent neural circuits underlying behavior in real-time. However, studying context-dependent locomotor perturbations has been challenging due to limitations in molecular tools and techniques for real-time manipulation of spinal cord circuits. New MethodWe developed a novel closed-loop optogenetic stimulation paradigm that utilizes DeepLabCut-Live pose estimation to manipulate primary sensory afferent activity at specific phases of the locomotor cycle in mice. A compact DeepLabCut model was trained to track hindlimb kinematics in real-time and integrated into the Bonsai visual programming framework. This allowed an LED to be triggered to photo-stimulate sensory neurons expressing channelrhodopsin at user-defined pose-based criteria, such as during the stance or swing phase. ResultsOptogenetic activation of nociceptive TRPV1+ sensory neurons during treadmill locomotion reliably evoked paw withdrawal responses. Photoactivation during stance generated a brief withdrawal, while stimulation during swing elicited a prolonged response likely engaging stumbling corrective reflexes. Comparison with Existing Methods: This new method allows for high spatiotemporal precision in manipulating spinal circuits based on the phase of the locomotor cycle. Unlike previous approaches, this closed-loop system can control for the state-dependent nature of sensorimotor responses during locomotion. ConclusionsIntegrating DeepLabCut-Live with optogenetics provides a powerful new approach to dissect the context-dependent role of sensory feedback and spinal interneurons in modulating locomotion. This technique opens new avenues for uncovering the neural substrates of state-dependent behaviors and has broad applicability for studies of real-time closed-loop manipulation based on pose estimation. ManuscriptO_ST_ABSHighlightsC_ST_ABSO_LIClosed-loop system probes state-dependent behaviors at pose-modulated instances C_LIO_LIBonsai integrates DeepLabCut models for real-time pose estimation during locomotion C_LIO_LIPhase-dependent TRPV1+ sensory afferent photostimulation elicits context-specific withdrawal responses C_LI

neuroscience↗

bioRxiv2025

Symmetries and continuous attractors in disordered neural circuits

A major challenge in neuroscience is reconciling idealized theoretical models with complex, heterogeneous experimental data. We address this challenge through continuous-attractor networks, which model how neural circuits represent continuous variables such as head direction or spatial location through collective dynamics. Classical continuous-attractor models rely on continuous symmetry in the recurrent weights to generate a manifold of stable states, predicting tuning curves that are identical up to shifts. However, mouse head-direction cells exhibit substantial heterogeneity in their responses, seemingly incompatible with this classical picture. We demonstrate that mammalian circuits could nevertheless rely on the same dynamical mechanisms as classical continuous-attractor models. We construct recurrent neural networks directly from experimental head-direction tuning curves that exhibit quasi-continuous-attractor dynamics, then develop a statistical generative process quantitatively capturing the structure of tuning heterogeneity. This enables large-N analysis, where we show through dynamical mean-field theory that these networks become equivalent to classical ring-attractor models, with Mexican-hat interactions and continuous symmetry that is spontaneously broken, leading to bump states. In the seemingly disordered weights, the continuous symmetry essential to classical models is reflected through eigenvalue degeneracies, positioning spectral structure as a target for detecting continuous-attractor circuits in connectome data. We extend this framework to two-dimensional symmetries, constructing grid-cell models that similarly reduce to classical toroidal attractors. Our work demonstrates that the dynamical mechanisms of classical continuous-attractor models may operate not only in small brains or idealized systems but also in complex mammalian circuits.

neuroscience↗

bioRxiv2021

A neural circuit basis for bilateral olfactory input-enhanced chemosensory avoidance navigation

Our understanding of how bilaterian animals utilize parallel input channels from paired sensory organs to optimize chemosensory behavior and the underlying neural circuit mechanisms are limited. Here we developed microfluidics-based behavioral and brainwide imaging platforms to study the neural integration of binasal inputs and chemosensory avoidance in larval zebrafish. We show that larval zebrafish efficiently escape from cadaverine-carrying streams by making more frequent swim bouts and larger undirected turns. Binasal inputs are strictly required for the nasal input-dependent component of klinokinesis, while each nasal input additively enhances angular orthokinesis. Throughout brain regions, including those along the olfactory processing pathways, a distributed neural representation with a wide spectrum of ipsilateral-contralateral nasal stimulus selectivity is maintained. Nonlinear sensory information gain with bilateral signal convergence is especially prominent in neurons weakly encoding unilateral cadaverine stimulus, and associated with stronger activation of sensorimotor neurons in the downstream brain regions. Collectively, these results provide insights into how the vertebrate model sums parallel input signals to guide chemosensory avoidance behavior.

neuroscience↗

bioRxiv2017

A zinc-finger fusion protein refines Gal4-defined neural circuits

The analysis of behavior requires that the underlying neuronal circuits are identified and genetically isolated. In several major model species--most notably Drosophila, neurogeneticists identify and isolate neural circuits with a binary heterologous expression-control system: Gal4-UASG. One limitation of Gal4-UASG is that expression patterns are often too broad to map circuits precisely. To help refine the range of Gal4 lines, we developed an intersectional genetic AND operator. Interoperable with Gal4, the new systems key component is a fusion protein in which the DNA-binding domain of Gal4 has been replaced with a zinc finger domain with a different DNA-binding specificity. In combination with its cognate binding site (UASZ) the zinc-finger-replaced Gal4 ( Zal1) was functional as a standalone transcription factor. Zal1 transgenes also refined Gal4 expression ranges when combined with UASGZ, a hybrid upstream activation sequence. In this way, combining Gal4 and Zal1 drivers captured restricted cell sets compared with single drivers and improved genetic fidelity. This intersectional genetic AND operation presumably derives from the action of a heterodimeric transcription factor: Gal4-Zal1. Configurations of Zal1-UASZ and Zal1-Gal4-UASGZ are versatile tools for defining, refining, and manipulating targeted neural expression patterns with precision.

neuroscience↗

bioRxiv2026

Constraints for spatially and temporally precise learning in a neural circuit model of reinforcement learning

Reinforcement learning is a key means by which animals learn appropriate actions in a given context. A large body of work suggests that such learning depends on interactions between cortico-basal ganglia circuits and the midbrain dopaminergic system, yet the underlying circuit mechanisms and plasticity rules are not fully understood. Here we present a biologically plausible, multi-region neural circuit model of songbird vocal learning and map it onto the actor-critic framework of reinforcement learning. In this model, stochastic spiking activity in the cortico-basal ganglia pathway implements action selection and drives behavioral exploration, while the pathways driving midbrain dopaminergic signaling evaluate behavioral outcomes and support a reward prediction error based learning rule that approximates stochastic gradient ascent. The model achieves millisecond-scale precise learning that matches observed behavior. We further use the model to examine two fundamental constraints on biological reinforcement learning. First, dopaminergic reinforcement signals are temporally imprecise, which can cause interference between neurons controlling actions that occur close in time. Second, dopaminergic signals are spatially imprecise, which can cause interference between neurons controlling different aspects of behavior but receiving a common reinforcement signal. By jointly modeling the actor and critic components of the circuit, we show that fast updating of reward prediction is crucial for precise and efficient learning under both forms of interference, and the model predicts the experimentally observed timescale of reward prediction updating. These results suggest a circuit-level mechanism by which biological systems achieve reinforcement learning despite the temporal and spatial limitations of global neuromodulatory signals.

neuroscience↗

bioRxiv2023

Dietary Availability Acutely Governs Puberty Onset via Hypothalamic Neural Circuit

Reproduction poses a substantial burden, especially for mammalian females. Puberty onset serves as a vital checkpoint, regulated based on the bodys energy state, to prevent inappropriate reproductive activity under malnutrition. However, the neural basis of this puberty checkpoint remains poorly understood. Here, we demonstrate that peripubertal malnutrition in female mice reduces the synchronous activity episodes of arcuate kisspeptin neurons (SEskiss), which are critical regulators of the gonadotropin axis. Improved dietary availability boosts SEskiss frequency, facilitating puberty onset. Using a viral-genetic approach, we show that the activating agouti-related protein neurons in the arcuate nucleus (ARCAgrp neurons), a hunger center, suppresses SEskiss, even with enough food. Conversely, loss-of-function of ARCAgrp neurons enhances SEskiss during malnutrition, partly promoting irregular sexual maturation. Collectively, a neural circuit connecting feeding to reproductive centers is responsible for disinhibiting SEskiss frequency based on dietary availability, which sheds light on the neural basis of puberty checkpoint. HighlightsO_LIThe pulsatile activity of arcuate kisspeptin neurons emerges and grows before vaginal opening. C_LIO_LIPubertal impairment resulting from malnutrition is associated with a reduction in the pulsatile activity of kisspeptin neurons. C_LIO_LIPubertal recovery by food availability follows the elevated pulsatile activity of kisspeptin neurons during catch-up growth. C_LIO_LIThe arcuate Agrp neurons suppress the frequency of pulsatile activity of kisspeptin neurons under negative energy balance. C_LI

neuroscience↗

bioRxiv2018

Glia mediated ionic balance in the stem cell niche is required for the proper proliferation of neurogenic tissues and wiring of neural circuits.

The cellular niche that surrounds stem cells modulates their self-renewal and proliferative properties. In the nervous system glial cells form part of the neural stem cell niche and express a wide variety of ion channels. While the physiological roles of ion channels in glia have been mainly studied in the mature nervous system, the contribution of glial ion channel function in the niche to nervous system development is poorly understood. To gain insight we explored the function of the Drosophila ClC-a chloride channel since its human ortholog CLCN2 is expressed in glial cells and impairment of its function results in neurodevelopmental disorders. We found ClC-a expressed in the niche in cortex glia. These glial cells are in close association with neurogenic tissues and also wrap neuronal cell bodies as they mature away from the niche. Characterization of loss of function ClC-a mutants showed these animals had smaller brains and widespread axon guidance defects. Here we show that ClC-a is required in cortex glia for the proliferation of neuroepithelial cells and neuroblasts, as well as for neuronal survival. We could also relate the axon guidance defects observed in photoreceptors to impaired proliferation in a neuroblast lineage that generates guidepost glial cells essential for this process. Taken together, our results show that ion channels expressed in glia forming part of the neural stem cell niche can have a significant impact on nervous system development. We propose that ion channels can non-autonomously modulate the number of neural progenitors and the progeny of neuroblast lineages, consequently affecting the correct assembly of neural circuits.

developmental biology↗