The Prop1-like homeobox gene unc-42 specifies the identity of synaptically connected neurons

eLife, Год журнала: 2021, Номер 10

Опубликована: Июнь 24, 2021

Many neuronal identity regulators are expressed in distinct populations of cells the nervous system, but their function is often analyzed only specific isolated cellular contexts, thereby potentially leaving overarching themes gene undiscovered. We show here that Caenorhabditis elegans Prop1-like homeobox unc-42 15 sensory, inter- and motor neuron classes throughout entire C. system. Strikingly, all expressing synaptically interconnected, prompting us to investigate whether controls functional properties this circuit perhaps also assembly these neurons into circuitry. found defines routes communication between interconnected by controlling expression neurotransmitter pathway genes, receptors, neuropeptides, neuropeptide receptors. Anatomical analysis mutant animals reveals defects axon pathfinding synaptic connectivity, paralleled molecules involved pathfinding, cell-cell recognition, connectivity. conclude establishes circuitry acting as a terminal selector functionally connected types. identify number additional transcription factors propose selectors may ‘circuit organizer factors’ control hypothesize such organizational be reflective not ontogenetic, phylogenetic trajectories establishment.

Язык: Английский

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Evolution of the vertebrate motor system — from forebrain to spinal cord

Current Opinion in Neurobiology, Год журнала: 2021, Номер 71, С. 11 - 18

Опубликована: Авг. 24, 2021

A comparison of the vertebrate motor systems oldest group now living vertebrates (lamprey) with that mammals shows there are striking similarities not only in basic organization but also regard to synaptic properties, transmitters and neuronal properties. The lamprey dorsal pallium (cortex) has a motor, visual somatosensory area, basal ganglia, including dopamine system, organized virtually identical way rodents. This applies midbrain, brainstem spinal cord. However, during evolution additional capabilities such as for control foreleg/arms, hands fingers have evolved. findings suggest when evolutionary lineages became separate around 500 million years ago, blueprint system had already

Язык: Английский

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The rhythm section: an update on spinal interneurons setting the beat for mammalian locomotion

Current Opinion in Physiology, Год журнала: 2019, Номер 8, С. 84 - 93

Опубликована: Янв. 30, 2019

Язык: Английский

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Recent Insights into the Rhythmogenic Core of the Locomotor CPG

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(3), С. 1394 - 1394

Опубликована: Янв. 30, 2021

In order for locomotion to occur, a complex pattern of muscle activation is required. For more than century, it has been known that the timing and stepping movements in mammals are generated by neural networks as central generators (CPGs), which comprise multiple interneuron cell types located entirely within spinal cord. A genetic approach recently successful identifying several populations neurons make up this network, well specific role they play during stepping. spite progress, identity responsible generating locomotor rhythm manner interconnected have yet be deciphered. review, we summarize key features considered expressed rhythm-generating describe different genetically defined classes interneurons proposed involved.

Язык: Английский

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Distinguishing subtypes of spinal locomotor neurons to inform circuit function and dysfunction

Current Opinion in Neurobiology, Год журнала: 2023, Номер 82, С. 102763 - 102763

Опубликована: Авг. 21, 2023

Язык: Английский

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Rapid generation of regionally specified CNS neurons by sequential patterning and conversion of human induced pluripotent stem cells

Stem Cell Research, Год журнала: 2020, Номер 48, С. 101945 - 101945

Опубликована: Авг. 3, 2020

The differentiation of patient-specific induced pluripotent stem cells (iPSCs) into specific neuronal subtypes has been exploited as an approach for modeling a variety neurological disorders. However, achieving highly pure population neurons is challenging when using directed methods, especially generated by complex and protracted protocols. In this study, we efficiently produced populations regionally specified CNS modified NGN2-Puromycin direct conversion protocol. protocol amenable across range iPSC lines, with more than 95% at day 21 positive the marker MAP2. We found that from resulted in central peripheral nervous system; however, incorporating short patterning step, eliminated these neurons. Furthermore, used step to control rostral-caudal identity. This sequential forebrain neurons, patterned SMAD inhibitors. Additionally, inhibitors WNT agonists were applied, anterior hindbrain excitatory containing VSX2/SHOX2 V2a interneurons. Overall, can be production patient-derived iPSCs, versatile system investigating early disease events disorders including Alzheimer's disease, motor spinal cord injury.

Язык: Английский

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Spinal Cord Injury Alters Spinal Shox2 Interneurons by Enhancing Excitatory Synaptic Input and Serotonergic Modulation While Maintaining Intrinsic Properties in Mouse

Journal of Neuroscience, Год журнала: 2021, Номер 41(27), С. 5833 - 5848

Опубликована: Май 18, 2021

Neural circuitry generating locomotor rhythm and pattern is located in the spinal cord. Most cord injuries (SCIs) occur above level of neurons; therefore, these circuits are a target for improving motor function after SCI. Despite being relatively intact below injury, undergoes substantial plasticity with loss descending control. Information regarding cell type-specific within limited. Shox2 interneurons (INs) have been linked to generation patterning, making them potential therapeutic restoration locomotion The goal present study was identify SCI-induced at INs complete thoracic transection model adult male female mice. Whole-cell patch-clamp recordings revealed minimal changes intrinsic excitability properties However, afferent stimulation resulted mixed excitatory inhibitory input uninjured mice which became predominantly were differentially modulated by serotonin (5-HT) concentration-dependent manner conditions but following SCI, 5-HT depolarized INs. 5-HT₇ receptors mediated effects on from both SCI mice, activation 5-HT_2B/2C enhanced only Overall, alters sensory pathways modulation enhance responses. Our findings provide relevant information response that could benefit strategies improve SIGNIFICANCE STATEMENT Current therapies gain control injury (SCI) circuitry. Improvements will require better understanding specific elements their controllers, including afferents serotonergic modulation. Here, we demonstrate interneurons, contribute pattering, remain induces modulation, enhancing excitation interneurons. impact future looking harness ultimate restoring functional

Язык: Английский

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Transformation of an early-established motor circuit during maturation in zebrafish

Cell Reports, Год журнала: 2022, Номер 39(2), С. 110654 - 110654

Опубликована: Апрель 1, 2022

Locomotion is mediated by spinal circuits that generate movements with a precise coordination and vigor. The assembly of these defined early during development; however, whether their organization function remain invariant throughout development unclear. Here, we show the first established fast circuit between two dorsally located V2a interneuron types four primary motoneurons undergoes major transformation in adult zebrafish compared what was reported larvae. There loss existing connections establishment new combined alterations mode, plasticity, strength synaptic transmission. In addition, this no longer serves as swim rhythm generator, but instead its components become embedded within escape control propulsion following initial turn. Our results thus reveal significant changes motor animals develop toward adulthood.

Язык: Английский

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A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure

Biosensors and Bioelectronics, Год журнала: 2024, Номер 267, С. 116754 - 116754

Опубликована: Сен. 14, 2024

Язык: Английский

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Properties of rhythmogenic currents in spinal Shox2 interneurons across postnatal development

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Май 11, 2025

Abstract Locomotor behaviours are performed by organisms throughout life, despite developmental changes in cellular properties, neural connectivity and biomechanics. The basic rhythmic activity the central nervous system underlying locomotion is considered to be generated via a complex interplay between network intrinsic properties. Within mature mammalian spinal locomotor circuitry, we have yet determine which properties of interneurons (INs) critical rhythmogenesis how they change during development. Here, combined whole cell patch clamp recordings, immunohistochemistry RNAscope targeting lumbar Shox2 INs mice, known involved rhythm generation. Our goal was postnatal expression voltage‐sensitive conductances, addition respective ion channels, INs. We show that subsets display persistent inward currents, M‐type potassium slow afterhyperpolarization T‐type calcium enhanced with age. By contrast, hyperpolarization‐activated A‐type currents were either found low prevalence neonatal, juvenile, adult or did not developmentally change. become more electrophysiologically diverse juvenile ages, when behaviour becomes weight‐bearing. Computational modelling used simulate reproduce electrophysiological experiments for representative make predictions regarding interactions experimentally recorded conductances bursting behaviour. results suggest shift magnitude rhythmogenic ionic corresponding channels may important image Key points locomotor‐related neurons contribute shaping maintaining activity. (INs), similar many other components well‐characterized neonatal mouse. Electrophysiological recordings reveal express ‘rhythmogenic properties’, including afterhyperpolarization, as well channels/RNA. Hierarchical clustering demonstrates seen related emergence types, largely defined strong current expression. data gain diversity age, from mice employ

Язык: Английский

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