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LSSS 2014-2015

2014LSSS2015

Life Sciences Seminar Series

 

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Silvia Arber

Biozentrum, University of Basel & Friedrich Miescher Institute for Biomedical Research, Basel

Specificity and modules in circuits for motor control

Selected Publications

Brainstem nucleus MdV mediates skilled forelimb motor tasks.Esposito MS, Capelli P, Arber S
Nature 2014 Apr 17; 508(7496):351-6

Abstract

Translating the behavioural output of the nervous system into movement involves interaction between brain and spinal cord. The brainstem provides an essential bridge between the two structures, but circuit-level organization and function of this intermediary system remain poorly understood. Here we use intersectional virus tracing and genetic strategies in mice to reveal a selective synaptic connectivity matrix between brainstem substructures and functionally distinct spinal motor neurons that regulate limb movement. The brainstem nucleus medullary reticular formation ventral part (MdV) stands out as specifically targeting subpopulations of forelimb-innervating motor neurons. Its glutamatergic premotor neurons receive synaptic input from key upper motor centres and are recruited during motor tasks. Selective neuronal ablation or silencing experiments reveal that MdV is critically important specifically for skilled motor behaviour, including accelerating rotarod and single-food-pellet reaching tasks. Our results indicate that distinct premotor brainstem nuclei access spinal subcircuits to mediate task-specific aspects of motor programs.

Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin.Pivetta C, Esposito MS, Sigrist M, Arber S
Cell 2014 Jan 30; 156(3):537-48

Abstract

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement.

Carving axon arbors to fit: master directs one kinase at a time.Satoh D, Arber S
Cell 2013 Jun 20; 153(7):1425-6

Abstract

Pyramidal neurons in the cortex require the master kinase LKB1 for early axon specification. Courchet et al. now uncover a later role for LKB1 and its tango with the downstream effector kinase NUAK1 in controlling terminal axonal branching through influencing mitochondrial motility in axons.

Motor antagonism exposed by spatial segregation and timing of neurogenesis.Tripodi M, Stepien AE, Arber S
Nature 2011 Nov 3; 479(7371):61-6

Abstract

Walking is a key motor behaviour of limbed animals, executed by contraction of functionally antagonistic muscle groups during swing and stance phases. Nevertheless, neuronal circuits regulating the activation of antagonistic extensor-flexor muscles remain poorly understood. Here we use monosynaptically restricted trans-synaptic viruses to elucidate premotor anatomical substrates for extensor-flexor control in mice. We observe a medio-lateral spatial segregation between extensor and flexor premotor interneurons in the dorsal spinal cord. These premotor interneuron populations are derived from common progenitor domains, but segregate by timing of neurogenesis. We find that proprioceptive sensory feedback from the periphery is targeted to medial extensor premotor populations and is required for extensor-specific connectivity profiles during development. Our findings provide evidence for a discriminating anatomical basis of antagonistic circuits at the level of premotor interneurons, and point to synaptic input and developmental ontogeny as key factors in the establishment of circuits regulating motor behavioural dichotomy.