Mixed synapses reconcile violations of the size principle in zebrafish spinal cord

Menelaou, Evdokia; Kishore, Sandeep P.; McLean, David L.

doi:10.7554/elife.64063

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…5C). This is consistent with peak excitatory drive normalized to cellular excitability, as reported previously (Menelaou et al, 2022).…”

Section: Resultssupporting

confidence: 92%

Cell-type-specific origins of locomotor rhythmicity at different speeds in larval zebrafish

Agha,

Kishore,

McLean

2024

Preprint

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Different speeds of locomotion require heterogeneous spinal populations, but a common mode of rhythm generation is presumed to exist. Here, we explore the cellular versus synaptic origins of spinal rhythmicity at different speeds by performing electrophysiological recordings from premotor excitatory interneurons in larval zebrafish. Chx10-labeled V2a neurons are divided into at least two subtypes proposed to play distinct roles in timing and intensity control. Consistent with distinct rhythm generating and output patterning functions within the spinal V2a population, we find that one subtype is recruited exclusively at slow or fast speeds and exhibits intrinsic cellular properties suitable for rhythmogenesis at those speeds, while the other subtype is recruited more reliably at all speeds and lacks appropriate rhythmogenic cellular properties. Unexpectedly, however, phasic firing patterns during locomotion in rhythmogenic and non-rhythmogenic subtypes are best explained by distinct modes of synaptic inhibition linked to cell-type and speed. At fast speeds reciprocal inhibition in rhythmogenic V2a neurons supports phasic firing, while recurrent inhibition in non-rhythmogenic V2a neurons helps pattern motor output. In contrast, at slow speeds recurrent inhibition in rhythmogenic V2a neurons supports phasic firing, while non-rhythmogenic V2a neurons rely on reciprocal inhibition alone to pattern output. Our findings suggest cell-type-specific, not common, modes of rhythmogenesis generate and coordinate different speeds of locomotion.

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“…5C). This is consistent with peak excitatory drive normalized to cellular excitability, as reported previously (Menelaou et al, 2022).…”

Section: Resultssupporting

confidence: 92%

Cell-type-specific origins of locomotor rhythmicity at different speeds in larval zebrafish

Agha,

Kishore,

McLean

2024

Preprint

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“…Although MNs within a pool typically fire in an orderly sequence, occasional violations of the recruitment hierarchy have been observed in many species, particularly during rapid, oscillating movements (Azevedo et al, 2020;Desmedt and Godaux, 1981;Menelaou et al, 2022;Smith et al, 1980). Our finding that MNs receive an equal number of excitatory and inhibitory synapses, as originally speculated by Henneman and colleagues (Henneman et al, 1965), suggests a mechanism for inversions of the recruitment hierarchy.…”

Section: Subverting the Recruitment Hierarchysupporting

confidence: 70%

“…Past work argues that constraining module activity with a recruitment hierarchy simplifies the problem of how the nervous system controls motor units with a range of neuromuscular properties (Hodson-Tole and Wakeling, 2009). However, violations of the recruitment hierarchy have been observed in many species, particularly during rapid, oscillating movements (Azevedo et al, 2020; Desmedt and Godaux, 1981; Menelaou et al, 2022; Smith et al, 1980). Recent work in primates demonstrated flexible relationships between MN firing rates that changed with the demands of a motor task (Marshall et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Synaptic architecture of leg and wing premotor control networks inDrosophila

Lesser

Azevedo

Phelps

et al. 2023

Preprint

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Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. Because individual muscles may be used in many different behaviors, MN activity must be flexibly coordinated by dedicated premotor circuitry, the organization of which remains largely unknown. Here, we use comprehensive reconstruction of neuron anatomy and synaptic connectivity from volumetric electron microscopy (i.e., connectomics) to analyze the wiring logic of motor circuits controlling theDrosophilaleg and wing. We find that both leg and wing premotor networks are organized into modules that link MNs innervating muscles with related functions. However, the connectivity patterns within leg and wing motor modules are distinct. Leg premotor neurons exhibit proportional gradients of synaptic input onto MNs within each module, revealing a novel circuit basis for hierarchical MN recruitment. In comparison, wing premotor neurons lack proportional synaptic connectivity, which may allow muscles to be recruited in different combinations or with different relative timing. By comparing the architecture of distinct limb motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.

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“…This proposes that larger mammalian spinal motoneurons with lower R inp were only recruited at high motor strengths and decruited first when the muscle relaxed. In zebrafish larvae up to 5 d old, the motoneuron recruitment also follows size principle, but in both excitatory and inhibitory interneurons only recruitment orders by R inp or dorsal-ventral positions are observed ( McLean et al, 2007 ; Menelaou et al, 2022 ). Although interneurons with high R inp are active at both slow and high swimming frequencies, those with low R inp are only recruited at high frequencies.…”

Section: Discussionmentioning

confidence: 98%

Mechanisms Underlying the Recruitment of Inhibitory Interneurons in Fictive Swimming in DevelopingXenopus laevisTadpoles

et al. 2023

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Developing spinal circuits generate patterned motor outputs while many neurons with high membrane resistances are still maturing. In the spinal cord of hatchling frog tadpoles of unknown sex, we found that the firing reliability in swimming of inhibitory interneurons with commissural and ipsilateral ascending axons was negatively correlated with their cellular membrane resistance. Further analyses showed that neurons with higher resistances had outward rectifying properties, low firing thresholds and little delay in firing evoked by current injections. Input synaptic currents these neurons received during swimming, either compound unitary current amplitudes or unitary synaptic current numbers, were scaled with their membrane resistances, but their own synaptic outputs were correlated with membrane resistances of their postsynaptic partners. Analyses of neuronal dendritic and axonal lengths and their activities in swimming and cellular input resistances did not reveal a clear correlation pattern. Incorporating these electrical and synaptic properties in a computer swimming model produced robust swimming rhythms whereas randomising input synaptic strengths led to the breakdown of swimming rhythms, coupled with less synchronised spiking in the inhibitory interneurons. We conclude that the recruitment of these developing interneurons in swimming can be predicted by cellular input resistances, but the order is opposite to the motor-strength based recruitment scheme depicted by Henneman’s size principle. This form of recruitment/integration order in development before the emergence of refined motor control is progressive potentially with neuronal acquisition of mature electrical and synaptic properties, among which the scaling of input synaptic strengths with cellular input resistance plays a critical role.SIGNIFICANCE STATEMENT:The mechanisms on how interneurons are recruited to participate circuit function in developing neuronal systems are rarely investigated. In two days old frog tadpole spinal cord, we found the recruitment of inhibitory interneurons in swimming is inversely correlated with cellular input resistances, opposite to the motor-strength based recruitment order depicted by Henneman’s size principle. Further analyses showed the amplitude of synaptic inputs neurons received during swimming was inversely correlated with cellular input resistances. Randomising/reversing the relation between input synaptic strengths and membrane resistances in modelling broke down swimming rhythms. Therefore, the recruitment or integration of these interneurons is conditional upon the acquisition of several electrical and synaptic properties including the scaling of input synaptic strengths with cellular input resistances.

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Mixed synapses reconcile violations of the size principle in zebrafish spinal cord

Cited by 9 publications

References 48 publications

Cell-type-specific origins of locomotor rhythmicity at different speeds in larval zebrafish

Cell-type-specific origins of locomotor rhythmicity at different speeds in larval zebrafish

Synaptic architecture of leg and wing premotor control networks inDrosophila

Mechanisms Underlying the Recruitment of Inhibitory Interneurons in Fictive Swimming in DevelopingXenopus laevisTadpoles

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