Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity

Boeri, Juliette; Meunier, Claude; Corronc, Hervé Le; Branchereau, Pascal; Timofeeva, Yulia; Lejeune, François‐Xavier; Mouffle, Christine; Arulkandarajah, Hervé; Legendre, Pascal; Czarnecki, Antonny

doi:10.7554/elife.62639

Cited by 3 publications

(2 citation statements)

References 90 publications

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“…Notably, in model neurons, further reducing spike height and AHP by down-scaling conductances rendered them unable to generate sustained trains of spikes (Fig. 6B), as observed in early embryonic development (Gao and Ziskind-Conhaim, 1998; Boeri et al, 2021). Conversely, as conductance densities were scaled up, spike height and AHP increased, and spike duration became shorter (Fig.…”

Section: Resultsmentioning

confidence: 85%

Interdependence of cellular and network properties in respiratory rhythmogenesis

Phillips,

Baertsch

2023

Preprint

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How breathing is generated by the preBötzinger Complex (preBötC) remains divided between two ideological frameworks, and the persistent sodium current (INaP) lies at the heart of this debate. AlthoughINaPis widely expressed, thepacemaker hypothesisconsiders it essential because it endows a small subset of neurons with intrinsic bursting or “pacemaker” activity. In contrast,burstlet theoryconsidersINaPdispensable because rhythm emerges from “pre-inspiratory” spiking activity driven by feed-forward network interactions. Using computational modeling, we discover that changes in spike shape can dissociateINaPfrom intrinsic bursting. Consistent with many experimental benchmarks, conditional effects on spike shape during simulated changes in oxygenation, development, extracellular potassium, and temperature alter the prevalence of intrinsic bursting and pre-inspiratory spiking without altering the role ofINaP. Our results support a unifying hypothesis whereINaPand excitatory network interactions, but not intrinsic bursting or pre-inspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.SIGNIFICANCE STATEMENTBreathing is a vital rhythmic process originating from the preBötzinger complex. Since its discovery in 1991, there has been a spirited debate about whether respiratory rhythm generation emerges as a network property or is driven by a subset of specialized neurons with rhythmic bursting capabilities, endowed by intrinsic currents. Here, using computational modeling, we propose a unifying data-driven model of respiratory rhythm generation which bridges the gap between these competing theories. In this model, both intrinsic cellular properties (a persistent sodium current) and network properties (recurrent excitation), but not intrinsic bursting, are essential and interdependent features of respiratory rhythm generation.

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Section: Resultsmentioning

confidence: 85%

Interdependence of cellular and network properties in respiratory rhythmogenesis

Phillips,

Baertsch

2023

Preprint

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“…This divergence develops postnatally. Indeed, the firing properties of Renshaw cells in early embryos (E12) (Boeri et al, 2018; Boeri et al, 2021) greatly differ from those expressed postnatally.…”

Section: Discussionmentioning

confidence: 99%

Spinal V1 Inhibitory Interneuron Clades Differ in Birthdate, Projections to Motoneurons and Heterogeneity

Worthy,

Anderson,

Lane

et al. 2023

Preprint

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Spinal cord interneurons play a crucial role in shaping motor output, but their precise identity and circuit connectivity remain unclear. Focusing on the cardinal class of inhibitory V1 interneurons, we define the diversity of four major V1 subsets according to timing of neurogenesis, genetic lineage-tracing, synaptic output to motoneurons, and synaptic inputs from muscle afferents. Birthdating delineates two early-born (Renshaw and Pou6f2) and two late-born V1 clades (Foxp2 and Sp8) suggesting sequential neurogenesis gives rise to different V1 clades. Neurogenesis did not correlate with motoneuron targeting. Early-born Renshaw cells and late-born Foxp2-V1 interneurons both tightly coupled to motoneurons, while early-born Pou6f2-V1 and late-born Sp8-V1 interneurons did not. V1-clades also greatly differ in cell numbers and diversity. Lineage labeling of the Foxp2-V1 clade shows it contains over half of all V1 interneurons and provides the largest inhibitory input to motoneuron cell bodies. Foxp2-V1 subgroups differ in neurogenesis and proprioceptive input. Notably, one subgroup defined by Otp expression and located adjacent to the lateral motor column exhibits substantial input from proprioceptors, consistent with some Foxp2-V1 cells at this location forming part of reciprocal inhibitory pathways. This was confirmed with viral tracing methods for ankle flexors and extensors. The results validate the previous V1 clade classification as representing unique interneuron subtypes that differ in circuit placement with Foxp2-V1s forming the more complex subgroup. We discuss how V1 organizational diversity enables understanding of their roles in motor control, with implications for the ontogenetic and phylogenetic origins of their diversity.SIGNIFICANCE STATEMENTSpinal interneuron diversity and circuit organization represents a key challenge to understand the neural control of movement in normal adults and also during motor development and in disease. Inhibitory interneurons are a core element of these spinal circuits, acting on motoneurons either directly or via premotor networks. V1 interneurons comprise the largest group of inhibitory interneurons in the ventral horn and their organization remains unclear. Here we present a comprehensive examination of V1 subtypes according to neurogenesis, placement in spinal motor circuits and motoneuron synaptic targeting. V1 diversity increases during evolution from axial-swimming fishes to limb-based mammalian terrestrial locomotion and this is reflected in the size and heterogeneity of the Foxp2-V1 clade which is closely associated to limb motor pools. We show Foxp2-V1 interneurons establish the densest and more direct inhibitory synaptic input to motoneurons, especially on cell bodies. This is of further importance because deficits on motoneuron cell body inhibitory V1 synapses and on Foxp2-V1 interneurons themselves have recently been shown to be affected at early stages of pathology in motor neurodegenerative diseases like amyotrophic lateral sclerosis.

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The alpha2 nicotinic acetylcholine receptor, a subunit with unique and selective expression in inhibitory interneurons associated with principal cells

Hilscher,

Mikulovic,

Perry

et al. 2023

Pharmacological Research

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Two opposite voltage-dependent currents control the unusual early development pattern of embryonic Renshaw cell electrical activity

Cited by 3 publications

References 90 publications

Interdependence of cellular and network properties in respiratory rhythmogenesis

Interdependence of cellular and network properties in respiratory rhythmogenesis

Spinal V1 Inhibitory Interneuron Clades Differ in Birthdate, Projections to Motoneurons and Heterogeneity

The alpha2 nicotinic acetylcholine receptor, a subunit with unique and selective expression in inhibitory interneurons associated with principal cells

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