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At least 253 records · Page 14Linked to original sources

bioRxiv2024

Birth order specified recruitment of motor circuits during spontaneous neural activity in zebrafish embryo

Modular organization of spinal neural circuits control dynamic regulation of locomotion. However, it is unknown when or how the distinct microcircuits emerge during development. We carried out high-resolution calcium imaging of neural activity driving the first motor behavior in one day old zebrafish embryo. During this period, at least two waves of neurogenesis occur to generate primary and secondary motoneurons. We found that embryos first display a single highly synchronized rhythmic neuronal circuit containing interneurons and motoneurons. Later, two distinct interneuron-motoneuron circuits emerge with one containing early-born motoneurons displaying low-frequency activity and the other containing later-born motoneurons with high-frequency activity. The results indicate a mode of birth order determined microcircuits where neurons that are born together are recruited together. Nicotine affected neuronal activity frequency, revealing a functional role for cholinergic signaling in the emergence of patterned spinal circuits. Indeed, we found aberrant arrhythmic synchronized activity in mutants for cholineacetyltransferase-a where acetylcholine is no longer synthesized. Overall, we reveal the sequential recruitment of birth order specified microcircuits during the emergence of the earliest motor behavior and highlight a conserved role for cholinergic signaling in regulating rhythmic neural activity in the embryonic spinal cord.

neuroscience↗

bioRxiv2026

Long-term Learning Induces Plastic Changes in Frontostriatal Circuits

Neural activity in frontal-striatal circuits underlies reinforcement learning. Traditional theories suggest that reinforcement signals, which drive learning, strengthen connections within the basal ganglia. This strengthening is believed to shift information processing from cortical regions to subcortical regions as learning becomes established over time. To examine this hypothesis, we trained macaques to associate multiple sets of images with their values. Selecting different images led to either an increase (+2, +1) or a decrease (-1, -2) in the number of tokens, which subsequently determined the amount of juice reward the macaques received. We simultaneously recorded neuronal activity from orbitofrontal cortex, ventral striatum, amygdala, and dorsomedial thalamic nucleus, analyzing the dynamic changes in these brain regions during both the initial learning and overlearned stages. The results indicated that as learning progressed from the initial stage to the overlearned stage, information processing shifted from the ventral striatum to the orbitofrontal cortex, corresponding to the abstraction from stimulus value to state value. This finding challenges traditional theories and provides a new perspective on the neural circuit mechanisms of learning.

neuroscience↗

bioRxiv2023

Simultaneous Electrophysiology and Optogenetic Perturbation of the Same Neurons in Chronically Implanted Animals using microLED Silicon Probes

Optogenetics are a powerful tool for testing how a neural circuit influences neural activity, cognition, and behavior. Accordingly, the number of studies employing optogenetic perturbation has grown exponentially over the last decade. However, recent studies have highlighted that the impact of optogenetic stimulation/silencing can vary depending on the construct used, the local microcircuit connectivity, extent/power of illumination, and neuron types perturbed. Despite these caveats, the majority of studies employ optogenetics without simultaneously recording neural activity in the circuit that is being perturbed. This dearth of simultaneously recorded neural data is due in part to technical difficulties in combining optogenetics and extracellular electrophysiology. The recent introduction of LED silicon probes, which feature independently controllable miniature LEDs embedded at several levels of each of multiple shanks of silicon probes, provides a tractable method for temporally and spatially precise interrogation of neural circuits. Here, we provide a protocol addressing how to perform chronic recordings using LED probes. This protocol provides a schematic for performing causal and reproducible interrogations of neural circuits and addresses all phases of the recording process: introduction of optogenetic construct, implantation of the LED probe, performing simultaneous optogenetics and electrophysiology in vivo, and post-processing of recorded data. SUMMARYThis method allows a researcher to simultaneously perturb neural activity and record electrophysiological signal from the same neurons with high spatial specificity using silicon probes with integrated LEDs. We outline a procedure detailing all stages of the process for performing reliable LED experiments in chronically implanted rodents.

neuroscience↗

bioRxiv2024

Neural circuit-selective, multiplexed pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception

Selective manipulation of neural circuits using optogenetics and chemogenetics holds great translational potential but requires genetic access to neurons. Here, we demonstrate a general framework for identifying genetic tool-independent, pharmacological strategies for neural circuit-selective modulation. We developed an economically accessible calcium imaging-based approach for large-scale pharmacological scans of endogenous receptor-mediated neural activity. As a testbed for this approach, we used the mouse locus coeruleus due to the combination of its widespread, modular efferent neural circuitry and its wide variety of endogenously expressed GPCRs. Using machine learning-based action potential deconvolution and retrograde tracing, we identified an agonist cocktail that selectively inhibits medial prefrontal cortex-projecting locus coeruleus neurons. In vivo, this cocktail produces synergistic antinociception, consistent with selective pharmacological blunting of this neural circuit. This framework has broad utility for selective targeting of other neural circuits under different physiological and pathological states, facilitating non-genetic translational applications arising from cell type-selective discoveries.

neuroscience↗

bioRxiv2025

The atypical adhesion GPCR ADGRA1 controls hippocampal inhibitory circuit function

Neural circuits contain a diverse array of inhibitory interneurons that control information processing. The cell surface receptors and signaling pathways that modulate cell type specific inhibitory synaptic function are unclear. Here, we identify the atypical adhesion GPCR ADGRA1 as essential for hippocampal PV and SST inhibitory synaptic function. ADGRA1 is selectively enriched in hippocampal PV and SST interneurons and localizes to a subset of synapses. ADGRA1 deletion in PV and SST interneurons impairs inhibitory synaptic inputs onto Dentate Gyrus granule cells and generates deficits in learning and memory. ADGRA1 engages several downstream G proteins, notably G13, a pathway important for the establishment of hippocampal PV interneuron synaptic networks. These results identify an orphan receptor pathway selective for specific inhibitory synapse subtypes and expand our understanding of the signaling mechanisms that establish hippocampal inhibitory circuits.

neuroscience↗

bioRxiv2019

Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits.

How neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here we investigate human cortical neuron development, plasticity and function, using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, and in vivo structural and functional imaging revealed that the human neurons develop morphologically and functionally following a prolonged developmental timeline, revealing the cell-intrinsic retention of juvenile properties of cortical neurons as an important mechanism underlying human brain neoteny. Following maturation, human neurons transplanted in the visual cortex display tuned responses to visual stimuli that are similar to those of mouse neurons, indicating capacity for physiological synaptic integration of human neurons in mouse cortical circuits. These findings provide new insights into human neuronal development, and open novel experimental avenues for the study of human neuronal function and diseases.\n\nHighlightsO_LICoordinated morphological and functional maturation of ESC-derived human cortical neurons transplanted in the mouse cortex.\nC_LIO_LITransplanted neurons display prolonged juvenile features indicative of intrinsic species-specific neoteny.\nC_LIO_LITransplanted neurons develop elaborate dendritic arbors, stable spine patterns and long-term synaptic plasticity.\nC_LIO_LIIn the visual cortex transplanted neurons display tuned visual responses that resemble those of the host cortical neurons.\nC_LI

neuroscience↗

bioRxiv2023

Neuropeptides with different cellular targets elicit similar output in a central pattern generating circuit

Neuromodulation lends flexibility to neural circuit operation but the general notion that different neuromodulators sculpt neural circuit activity into distinct and characteristic patterns is complicated by interindividual variability. In addition, some neuromodulators converge onto the same signaling pathways, with similar effects on neurons and synapses. We compared the effects of three neuropeptides on the rhythmic pyloric circuit in the crab Cancer borealis stomatogastric nervous system. Proctolin (PROC), crustacean cardioactive peptide (CCAP), and red pigment concentrating hormone (RPCH) all activate the same modulatory inward current, IMI, and have convergent actions on synapses. However, while PROC targets all four neuron types in the core pyloric circuit, CCAP and RPCH target the same subset of only two neurons. After removal of spontaneous neuromodulator release, none of the neuropeptides restored the control cycle frequency, but all restored the relative timing between neuron types. Consequently, differences between neuropeptide effects were mainly found in the spiking activity of different neuron types. We performed statistical comparisons using the Euclidean distance in the multidimensional space of normalized output attributes to obtain a single measure of difference between modulatory states. Across preparations, circuit output in PROC was distinguishable from CCAP and RPCH, but CCAP and RPCH were not distinguishable from each other. However, we argue that even between PROC and the other two neuropeptides, population data overlapped enough to prevent reliable identification of individual output patterns as characteristic for a specific neuropeptide. We confirmed this notion by showing that blind classifications by machine learning algorithms were only moderately successful. Significance StatementIt is commonly assumed that distinct behaviors or circuit activities can be elicited by different neuromodulators. Yet it is unknown to what extent these characteristic actions remain distinct across individuals. We use a well-studied circuit model of neuromodulation to examine the effects of three neuropeptides, each known to produce a distinct activity pattern in controlled studies. We find that, when compared across individuals, the three peptides elicit activity patterns that are either statistically indistinguishable or show too much overlap to be labeled characteristic. We ascribe this to interindividual variability and overlapping subcellular actions of the modulators. Because both factors are common in all neural circuits, these findings have broad significance for understanding the chemical neuromodulatory actions while considering interindividual variability.

neuroscience↗

bioRxiv2021

Help or flight: Neural defensive circuits promote helping under threat in humans

Empathy for others distress has long been considered the driving force of helping. However, when deciding to help others in danger, one must consider not only their distress, but also the risk to oneself. Whereas the role of self-defence in helping has been overlooked in human research, studies in other animals indicate defensive responses are necessary for the protection of conspecifics. In this pre-registered study (N=49), we demonstrate that human defensive neural circuits are implicated in helping others under threat. Participants underwent fMRI scanning while deciding whether to help another participant avoid aversive electrical shocks, at the risk of also being shocked. We found that higher engagement of neural circuits that coordinate fast escape from self-directed danger (including the insula, PAG and ACC) facilitated decisions to help others. Importantly, using Representational Similarity Analysis, we found that the strength with which the amygdala and insula uniquely represented the threat to oneself (and not the others distress) predicted helping. Our findings indicate that in humans, as other mammals, defensive mechanisms play a greater role in helping behaviour than previously understood.

neuroscience↗

bioRxiv2024

Evolution of the neural sex-determination system in insects: The doublesex homolog in crickets functions as an X-linked masculinizing factor to regulate morphological but not behavioral sexual dimorphism

In animals, sex-specific social behaviors, such as courtship and aggression, are controlled by sex-specific neural circuits. To understand the neural mechanisms of sex-specific social behaviors from a comparative perspective, it is necessary to understand the sex determination mechanisms of neural circuits and their evolution across animal lineages. To address this, I have focused on the evolution of the neural sex determination system in insects. In the fruit fly Drosophila melanogaster, a model insect with powerful genetics, the molecular mechanisms underlying neuronal sex determination are well understood, and two transcription factor genes, fruitless and doublesex (dsx), have been identified as terminal differentiators. In contrast, those in direct-developing insects, which diverged from the holometabolous lineage, including Drosophila, about 400 million years ago, remain unclear. My previous studies found that the fruitless homolog is unlikely to be integrated into the neuronal sex determination system in direct-developing insects. In this study, I investigated whether the dsx homolog in direct-developing insects contributes to neuronal sex determination to form neural circuits that regulate adult social behaviors. I identified the dsx homolog in the two-spotted cricket Gryllus bimaculatus (Gryllus dsx gene) and revealed that it has a unique isoform configuration, and its encoded proteins contain a cryptic DNA-binding DM domain with accumulated amino acid substitutions. A knockout study revealed that the Gryllus dsx gene functions as an X-linked morphological masculinizing factor but does not determine the sexual orientation or behavioral patterns of adult social behavior in crickets. These results suggest that, at least in crickets, an unknown sex determination factor(s) other than fruitless and dsx plays a central role in neuronal sex determination.

evolutionary biology↗

bioRxiv2025

Serotonergic signaling governs C. elegans sensory response to conflicting olfactory stimuli

Neural circuits that consolidate sensory cues are essential for neurological functioning. Neural circuits that perform sensory integration can vary greatly because the sensory processing regions of the brain employ various neural motifs. Here, we investigate a neural circuit that mediates the response to conflicting olfactory stimuli in C. elegans. We concurrently expose animals to an aversive dispersal pheromone, osas#9, and an attractive bacterial extract. While worms usually avoid osas#9 alone, they suppress this avoidance behavior in the presence of a bacterial extract. Loss-of-function mutants and cell-specific rescues reveal that serotonergic signaling from the ADF neuron is essential for bacterial extract-induced osas#9 avoidance attenuation. The inhibitory serotonin receptor, MOD-1, which is widely expressed on interneurons and motor neurons, is required for this sensory integration, suggesting that serotonin acts in an inhibitory manner. By performing calcium imaging on the ADF neurons in synaptic signaling (unc-13) and peptidergic (unc-31) signaling mutant backgrounds, we show that the ADF neurons require input from other neurons, likely the ASK neurons, to respond to food extracts. We reveal a cue integration neural circuit in which serotonergic signaling at the sensory neuron level silences an aversive neural signal. SignificanceAnimals use sensory cues to make behavioral choices and sometimes, these cues convey opposite information. The nervous system consolidates competing sensory cues to create a coherent response to external stimuli. The neural circuits that govern this process are important, and still largely unknown. We use C. elegans, a soil-dwelling nematode, to uncover a neural circuit governing the consolidation of competing cues by concurrently exposing worms to positive and negative stimuli . We find that the neurotransmitter serotonin can suppress aversive neural signals created by negative stimuli. These results show the important neurological role that serotonin plays in modulating neural signals.

neuroscience↗

bioRxiv2023

Comodulation reduces interindividual variability of circuit output

2Ionic current levels of identified neurons vary substantially across individual animals. Yet, under similar conditions, neural circuit output can be remarkably similar, as evidenced in many motor systems. All neural circuits are influenced by multiple neuromodulators which provide flexibility to their output. These neuromodulators often overlap in their actions by modulating the same channel type or synapse, yet have neuron-specific actions resulting from distinct receptor expression. Because of this different receptor expression pattern, in the presence of multiple convergent neuromodulators, a common downstream target would be activated more uniformly in circuit neurons across individuals. We therefore propose that a baseline tonic (non-saturating) level of comodulation by convergent neuromodulators can reduce interindividual variability of circuit output. We tested this hypothesis in the pyloric circuit of the crab, Cancer borealis. Multiple excitatory neuropeptides converge to activate the same voltage-gated current in this circuit, but different subsets of pyloric neurons have receptors for each peptide. We quantified the interindividual variability of the unmodulated pyloric circuit output by measuring the activity phases, cycle frequency and intraburst spike number and frequency. We then examined the variability in the presence of different combinations and concentrations of three neuropeptides. We found that at mid-level concentration (30 nM) but not at near-threshold (1 nM) or saturating (1 M) concentrations, comodulation by multiple neuropeptides reduced the circuit output variability. Notably, the interindividual variability of response properties of an isolated neuron was not reduced by comodulation, suggesting that the reduction of output variability may emerge as a network effect. 3 Significance StatementNeuromodulation has been explored as a mechanism to provide flexibility to the output of neural circuits. All neural circuits are subject to neuromodulation by multiple substances. Here, we propose a different but complimentary role for neuromodulation. We use two general facts about neuromodulation to show that convergent comodulation at tonic mid-concentration levels reduces interindividual variability of neural circuit output. These facts are that 1) Multiple neuromodulators can have convergent actions on the same subcellular substrates and 2) Neurons express different neuromodulator receptors at different levels.

neuroscience↗

bioRxiv2023

Building functional circuits in multispecies brains.

The genome is the ultimate architect of the brain. Its evolutionary variations build the neural circuits that endow each species with its innate senses and behaviors. A central question for neuroscience and translational medicine is whether neural circuits from two species can be made to function in an intact brain. Here, we establish genetic tools and use blastocyst complementation to selectively build and test interspecies neural circuits in rat-mouse brains. Despite [~]10-20 million years of evolution and prominent differences in brain size and cellular composition, rat pluripotent stem cells injected into mouse blastocysts widely populate and persist in the mouse brain. Unexpectedly, the mouse niche reprograms the birthdates of cortical and hippocampal rat neurons, where they also form synaptically active rat-mouse circuits. By genetically disabling host olfactory circuitry, we show that rat neurons restore synaptic information flow from the nose to the cortex. Rat neurons can also rescue a primal olfactory behavior (food-seeking), though less than mouse controls. By enabling a mouse to sense the world with rat neurons, we highlight the power of interspecies neural blastocyst complementation to uncover mechanisms of neural circuit development and evolution, and to inform efforts to rescue neural circuits affected by injury or disease.

developmental biology↗

bioRxiv2025

Cross-species comparative connectomics reveals the evolution of an olfactory circuit

Animal behavioural diversity ultimately stems from variation in neural circuitry, yet how central neural circuits evolve remains poorly understood. Studies of neural circuit evolution often focus on a few elements within a network. However, addressing fundamental questions in evolutionary neuroscience, such as whether some elements are more evolvable than others, requires a more global and unbiased approach. Here, we used synapse-level comparative connectomics to examine how an entire olfactory circuit evolves. We compared the full antennal lobe connectome of the larvae of two closely related Drosophila species, D. melanogaster and D. erecta, which differ in their ecological niches and odour-driven behaviours. We found that evolutionary change is unevenly distributed across the network. Some features, including neuron types, neuron numbers and interneuron-to-interneuron connectivity, are highly conserved. These conserved elements delineate a core circuit blueprint presumably required for fundamental olfactory processing. Superimposed on this scaffold, we find rewiring changes that mirror each species ecologies, including a systematic shift in the excitation-to-inhibition balance in the feedforward pathways. We further show that some neurons have changed more than others, and that even within individual neurons some synaptic elements remain conserved while others display major species-specific changes, suggesting evolutionary hot-spots within the circuit. Our findings reveal constrained and adaptable elements within olfactory networks, and establish a framework for identifying general principles in the evolution of neural circuits underlying behaviour.

neuroscience↗

bioRxiv2021

Hunchback activates Bicoid in post-mitotic Pair1 neurons to regulate synapse number

The proper formation and function of neural circuits is crucial for cognition, sensation, and behavior. Neural circuits are highly-specific, and this specificity is dependent on neurons developing key features of their individual identities: morphology, anatomical location, molecular expression and biophysiological properties. Previous research has demonstrated that a neurons identity is, in part, generated by the temporal transcription window the neuron is born in, and the homeodomain transcription factors expressed in the mature neuron. However, whether temporal transcription factors and homeodomain transcription factors regulate neural circuit formation, maintenance and function remains unknown. Here, we utilize a well-characterized neural circuit in the Drosophila larvae, the Pair1 neuron. We determined that in the Pair1 neuron, the temporal transcription factor Hunchback activates the homeodomain transcription factor Bicoid (Bcd). Both Hunchback and Bcd are expressed in Pair1 throughout larval development. Interestingly, Hunchback and Bcd were not required in Pair1 for neurotransmitter identity or axonal morphology, but were required for synapse density. We found that these transcription factors were functioning post-mitotically in Pair1 to regulate synapse density. Additionally, knocking down Hunchback and Bcd in Pair1 neurons disrupted the behavioral output of the circuit. We utilized the genetic tool TransTango to determine that Hunchback function in Pair1 is to repress forming synapses with erroneous neurons. To our knowledge, these data are the first to show Hunchback activating Bcd expression, as well as the first to demonstrate a role for Hunchback and Bcd post-mitotically.

neuroscience↗

bioRxiv2021

Tracing cortical circuits in humans and non-human primates from high resolution connectomic, transcriptomic, and temporal dimensions

The neural circuits that support human cognition are a topic of enduring interest. Yet, the lack of tools available to map human brain circuits has precluded our ability to trace the human and non-human primate connectome. We harnessed high-resolution connectomic, anatomic, and transcriptomic data to investigate the evolution and development of frontal cortex circuitry. We applied machine learning to RNA sequencing data to find corresponding ages between humans and macaques and to compare the development of circuits across species. We transcriptionally defined neural circuits by testing for associations between gene expression and white matter maturation. We then considered transcriptional and structural growth to test whether frontal cortex circuit maturation is unusually extended in humans relative to other species. We also considered gene expression and high-resolution diffusion MR tractography of adult brains to test for cross-species variation in frontal cortex circuits. We found that frontal cortex circuitry development is extended in primates, and concomitant with an expansion in cortico-cortical pathways compared with mice in adulthood. Importantly, we found that these parameters varied relatively little across humans and studied primates. These data identify a surprising collection of conserved features in frontal cortex circuits across humans and Old World monkeys. Our work demonstrates that integrating transcriptional and connectomic data across temporal dimensions is a robust approach to trace the evolution of brain connectomics in primates. Significance StatementWe lack appropriate tools to visualize the human brain connectome. We develop new approaches to study connections in the human and non-human primate brains. The integration of transcription with structure offers an unprecedented opportunity to study circuitry evolution. Our integrative approach finds corresponding ages across species and transcriptionally defines neural circuits. We used this information to test for variation in circuit maturation across species and found a surprising constellation of similar features in frontal cortex neural circuits across humans and primates. Integrating across scales of biological organization expands the repertoire of tools available to study connections in primates, which opens new avenues to study connections in health and diseases of the human brain.

neuroscience↗

bioRxiv2018

Inhibition and excitation shape activity selection: effect of oscillations in a decision-making circuit

Decision-making is a complex task and requires adaptive mechanisms that facilitate efficient behaviour. Here, we consider a neural circuit that guides the behaviour of an animal in ongoing binary choice tasks. We adopt an inhibition motif from neural network theory and propose a dynamical system characterized by nonlinear feedback, which links mechanism (the implementation of the neural circuit) and function (increasing reproductive value). A central inhibitory unit influences evidence-integrating excitatory units, which in our terms correspond to motivations competing for selection. We determine the parameter regime where the animal exhibits improved decision-making behaviour, and explain different behavioural outcomes by making the link between bifurcation analysis of the nonlinear neural circuit model and decision-making performance. We find that the animal performs best if it tunes internal parameters of the neural circuit in accordance with the underlying bifurcation structure. In particular, variation of inhibition strength and excitation-over-inhibition ratio have a crucial effect on the decision outcome, by allowing the animal to break decision deadlock and to enter an oscillatory phase that describes its internal motivational state. Our findings indicate that this oscillatory phase may improve the overall performance of the animal in an ongoing foraging task. Our results underpin the importance of an integrated functional and mechanistic study of animal activity selection.\n\nAuthor summaryOrganisms frequently select activities, which relate to economic, social and perceptual decision-making problems. The choices made may have substantial impact on their lives. In foraging decisions, for example, animals aim at reaching a target intake of nutrients; it is generally believed that a balanced diet improves reproductive success, yet little is known about the underlying mechanisms that integrate nutritional needs within the brain. In our study, we address this coupling between physiological states and a decision-making circuit in the context of foraging decisions. We consider a model animal that has the drive to eat or drink. The motivation to select and perform one of these activities (i.e. eating or drinking), is processed in artificial neuronal units that have access to information on how hungry and thirsty the animal is at the point it makes the decision. We show that inhibitory and excitatory mechanisms in the neural circuit shape ongoing binary decisions, and we reveal under which conditions oscillating motivations may improve the overall performance of the animal. Our results indicate that inefficient or pathological decision-making may originate from suboptimal modulation of excitation and inhibition in the neurobiological network.

neuroscience↗

bioRxiv2023

Relationship between neural activity and neuronal cell fate in regenerating Hydra revealed by cell-type specific imaging

Understanding how neural circuits are regenerated following injury is a fundamental question in neuroscience. Hydra is a powerful model for studying this process because it has significant and reproducible regenerative abilities, a simple and transparent body that allows for whole nervous system imaging, and established methods for creating transgenics with cell-type-specific expression. In addition, cnidarians such as Hydra split from bilaterians (the group that encompasses most model organisms used in neuroscience) over 500 million years ago, so similarities with other models likely indicates deeply conserved biological processes. Hydra is a long-standing regeneration model and is an emerging model for neuroscience; however, relatively little is known regarding the restoration of neural activity and behavior following significant injury. In this study, we ask if regenerating neurons reach a terminal cell fate and then reform functional neural circuits, or if neural circuits regenerate first and then guide the constituent cells toward their terminal fate. To address this question, we developed a dual-expression transgenic Hydra line that expresses a cell-type-specific red fluorescent protein (tdTomato) in ec5 peduncle neurons, and a calcium indicator (GCaMP7s) in all neurons. This transgenic line allowed us to monitor neural activity while we simultaneously track the reappearance of terminally differentiated ec5 neurons as determined by the expression of tdTomato. Using SCAPE (Swept Confocally Aligned Planar Excitation) microscopy, we tracked both calcium activity and expression of tdTomato-positive neurons in 3D with single-cell resolution during regeneration of Hydras aboral end. We observed tdTomato expression in ec5 neurons approximately four hours before the neural activity begins to display synchronized patterns associated with a regenerated neural circuit. These data suggest that regenerating neurons undergo terminal differentiation prior to re-establishing their functional role in the nervous system. The combination of dynamic imaging of neural activity and gene expression during regeneration make Hydra a powerful model system for understanding the key molecular and functional processes involved in neuro-regeneration following injury.

neuroscience↗

bioRxiv2019

Thermal stimulation temperature is encoded as a firing rate in a Hydra nerve ring

Many animals that lose neural tissue due to injury or disease have the ability to maintain their behavioral abilities by regenerating new neurons or reorganizing existing neural circuits. However, most small model organisms used for neuroscience like nematodes and flies lack this high degree of neural plasticity. These animals often show significant behavioral deficits if they lose even a single neuron. Here we show that the small freshwater cnidarian Hydra vulgaris can maintain stable sensory motor behaviors even after losing half of the neurons in its body. Specifically, we find that both the behavioral and neural response to a rapid change in temperature is maintained if we make their nervous system roughly 50% smaller by caloric restriction or surgery. These observations suggest that Hydra provides a rich model for studying how animals maintain stable sensory-motor responses within dynamic neural circuit architectures, and may lead to general principles for neural circuit plasticity and stability. Significance StatementThe ability of the nervous system to restore its function following injury is key to survival for many animals. Understanding this neural plasticity in animals across the phylogenetic tree would help reveal fundamental principles of this important ability. To our knowledge, the discovery of a set of neurons in the jellyfish polyp Hydra vulgaris that stably support a response to thermal stimulation is the first demonstration of large-scale neural plasticity in a genetically tractable invertebrate model organism. The small size and transparency of Hydra suggests that it will be possible to study large-scale neural circuit plasticity in an animal where one can simultaneously image the activity of every neuron.

neuroscience↗