V2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements

Song, Jianren; Dahlberg, Elin; Manira, Abdeljabbar El

doi:10.1038/s41467-018-05827-9

Cited by 56 publications

(83 citation statements)

References 79 publications

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“…Although substantial progress has been made in describing spinal cell types and projection patterns 2,4,32,42,43,44,45 remarkably little is known about connectivity in motor circuits. Indeed, the size and extent of the neuronal population involved in generating motor activity are unknown, and essential features of graph theory, such convergence versus divergence, degree distributions, 29 and sparseness remain open issues.…”

Section: Discussionmentioning

confidence: 99%

Decoupling of timescales reveals sparse convergent CPG network in the adult spinal cord

Radosevic

Willumsen

Petersen

et al. 2018

Preprint

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During the generation of rhythmic movements, most spinal neurons receive an oscillatory synaptic drive. The neuronal architecture underlying this drive is unknown, and the corresponding network size and sparseness have not yet been addressed. If the input originates from a small central pattern generator (CPG) with dense divergent connectivity, it will induce correlated input to all receiving neurons, while sparse convergent wiring will induce a weak correlation, if any. Here, we use pairwise recordings of spinal neurons to measure synaptic correlations and thus infer the wiring architecture qualitatively. A strong correlation on a slow timescale implies functional relatedness and a common source, which will also cause correlation on fast timescale due to shared synaptic connections. However, we consistently find marginal coupling between slow and fast correlations regardless of neuronal identity. This suggests either sparse convergent connectivity or a CPG network with recurrent inhibition that actively decorrelates common input.Movement is an essential part of our daily lives, and disorders of the motor system, such as spasticity, amyotrophic lateral sclerosis, and spinal cord injury are particularly debilitating for individuals. Simple rhythmic movements, such as walking and breathing, have constituted models for fundamental aspects of the motor system. In spite of extensive investigations, 1, 2, 3, 4, 5, 6 the connectivity of the network responsible for generating the motor activity remains unknown. A circuit component, known as a central pattern generator (CPG), is believed to transmit command signals to motoneurons and local premotor interneurons. 7,8,9,10 Although the size of the respiratory motor network, i.e. the preBötzinger complex, 1, 11 is well-known, the size and wiring of other CPG networks are not well understood. A feedforward organization is often proposed between groups of neurons or modules, which exhibit alternating rhythmic bursting 12 (Fig. 1a). Common drive modules are thought to be small, e.g., the preBötzinger complex has only 600 neurons, 1 which provides rhythmic drive for the rest of the network. The projection is also believed to diverge onto a much larger population of receiving neurons. 13,14,15 Thus, the receiving neurons would share the same connections via a dense divergent connectivity ( Fig. 1b). Since the transmission is communicated by action potentials, which are precise in time, a dense connectivity will manifest as a strong temporal correlation between synaptic potentials in the receiving neurons, and this correlation can be verified experimentally through pairwise recordings. If the drive network is not a small but rather a large population, however, the receiver neurons are likely to collect sparse convergent input without correlation (Fig. 1c). Hence, the assessment of correlation CPG connectivity from decoupled timescales Extensor network Flexor network extensor Common drive Common drive flexor IN IN MN MN MN e x o r e x te ns or knee MN Dense Common drive Sparse c b ...

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Section: Discussionmentioning

confidence: 99%

Decoupling of timescales reveals sparse convergent CPG network in the adult spinal cord

Radosevic

Willumsen

Petersen

et al. 2018

Preprint

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“…Previous studies on the anatomical and functional organization of the V2a interneurons neglected the possibility that they might co-express and potentially co-release neurotransmitters other than glutamate (Ampatzis et al, 2014;Ausborn et al, 2012;Dougherty and Kiehn, 2010). However, earlier studies on zebrafish (Ampatzis et al, 2014;Ausborn et al, 2012;Song et al, 2018) and mice (Al-Mosawie et al, 2007;Zhong et al, 2011) clearly demonstrated that the V2a interneurons are functionally heterogeneous. In particular, the V2a interneurons in adult zebrafish form three discrete functional subpopulations that are incrementally recruited at different speeds of locomotion, and their recruitment pattern is not topographically organized (Ampatzis et al, 2014;Ausborn et al, 2012;Song et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate our findings and the extent of neurotransmitter co-expression and dynamics, we performed a proof-of-concept analysis focusing on one of the most well-characterized spinal interneuron populations, the V2a interneurons (Arber, 2012;Goulding, 2009;Kiehn, 2016;2011). V2a interneurons are one of the most important excitatory neuronal classes for the operation of the vertebrate locomotor network (Al-Mosawie et al, 2007;Crone et al, 2008;Dougherty and Kiehn, 2010;Hayashi et al, 2018;Joshi et al, 2009;Lundfald et al, 2007;Zhong et al, 2011), as demonstrated by studies on zebrafish (Ampatzis et al, 2014;Ausborn et al, 2012;Eklöf-Ljunggren et al, 2012;Kimura et al, 2006;McLean et al, 2008;McLean and Fetcho 2009;Menelaou et al, 2014;Song et al, 2018). In keeping with previous reports (Ampatzis et al, 2014), we detected 23.59 ± 0.503 V2a interneurons (n = 22 zebrafish; Figure S4B) per hemisegment in the adult zebrafish spinal cord.…”

Section: V2a Interneuron Neurotransmitter Diversity: a Proof-of-concementioning

confidence: 99%

Large scale analysis of the diversity and complexity of the adult spinal cord neurotransmitter typology

Pedroni

Ampatzis

2019

Preprint

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The development of nervous system atlases is a fundamental pursuit in neuroscience, since they constitute a fundamental tool to improve our understanding of the nervous system and behavior. As such, neurotransmitter maps are valuable resources to decipher the nervous system organization and functionality. We present here the first comprehensive quantitative map of neurons found in the adult zebrafish spinal cord. Our study overlays detailed information regarding the anatomical positions, sizes, neurotransmitter phenotypes, and the projection patterns of the spinal neurons. We also show that neurotransmitter co-expression is much more extensive than previously assumed, suggesting that spinal networks are more complex than first recognized. As a first direct application of this atlas, we investigated the neurotransmitter diversity in the putative glutamatergic V2a interneuron assembly of the adult zebrafish spinal cord. These studies shed new light on the diverse and complex functions of this important interneuron class in the neuronal interplay governing the precise operation of the central pattern generators.

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“…Although BPNs are necessary for fast walking, the ability of BPNs to drive different walking speeds at different stimulation frequencies, provides an opportunity to examine downstream mechanisms for speed control. Recent studies in zebrafish (Ampatzis et al, 2014;Song et al, 2018) show a gradient of recruitment of distinct premotor circuits at increasing swimming speeds. In Drosophila, recent work (Azevedo et al 2019) has characterized distinct motor neurons recruited in a similar manner as leg movements accelerate.…”

Section: Bolt Protocerebral Neurons (Bpns) Drive Fast Straight Forwamentioning

confidence: 99%

Two brain pathways initiate distinct forward walking programs inDrosophila

Bidaye¹,

Laturney²,

Chang³

et al. 2019

Preprint

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An animal at rest or engaged in stationary behaviors can instantaneously initiate goaldirected walking. How descending brain inputs trigger rapid transitions from a non-walking state to an appropriate walking state is unclear. Here, we identify two specific neuronal classes in the Drosophila brain that drive two distinct forward walking programs in a context-specific manner.The first class, named P9, consists of descending neurons that drive forward walking with ipsilateral turning. P9 receives inputs from central courtship-promoting neurons and visual projection neurons and is necessary for a male to track a female during courtship. The second class comprises novel, higher order neurons, named BPN, that drives straight, forward walking. BPN is required for high velocity walking and is active during long, fast, straight walking bouts. Thus, this study reveals separate brain pathways for object-directed steering and fast straight walking, providing insight into how the brain initiates different walking programs.Raw and processed data along with custom Matlab analysis scripts will be made available upon request. Design files for custom parts will be available upon request.Ache, J.M., Haupt, S.S., and Dürr, V. (2015). A direct descending pathway informing locomotor networks about tactile sensor movement.

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V2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements

Cited by 56 publications

References 79 publications

Decoupling of timescales reveals sparse convergent CPG network in the adult spinal cord

Decoupling of timescales reveals sparse convergent CPG network in the adult spinal cord

Large scale analysis of the diversity and complexity of the adult spinal cord neurotransmitter typology

Two brain pathways initiate distinct forward walking programs inDrosophila

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