Dataset Information

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits.

ABSTRACT: Layering of neural circuits facilitates the separation of neurons with high spatial sensitivity from those that play integrative temporal roles. Although anatomical layers are readily identifiable in the brain, layering is not structurally obvious in the spinal cord. But computational studies of motor behaviors have led to the concept of layered processing in the spinal cord. It has been postulated that spinal V3 interneurons (INs) play multiple roles in locomotion, leading us to investigate whether they form layered microcircuits. Using patch-clamp recordings in combination with holographic glutamate uncaging, we demonstrate focal, layered modules, in which ventromedial V3 INs form synapses with one another and with ventrolateral V3 INs, which in turn form synapses with ipsilateral motoneurons. Motoneurons, in turn, provide recurrent excitatory, glutamatergic input to V3 INs. Thus, ventral V3 interneurons form layered microcircuits that could function to ensure well-timed, spatially specific movements.

SUBMITTER: Chopek JW

PROVIDER: S-EPMC6180347 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits.

Chopek Jeremy W JW Nascimento Filipe F Beato Marco M Brownstone Robert M RM Zhang Ying Y

Cell reports 20181001 1

Layering of neural circuits facilitates the separation of neurons with high spatial sensitivity from those that play integrative temporal roles. Although anatomical layers are readily identifiable in the brain, layering is not structurally obvious in the spinal cord. But computational studies of motor behaviors have led to the concept of layered processing in the spinal cord. It has been postulated that spinal V3 interneurons (INs) play multiple roles in locomotion, leading us to investigate whe ...[more]

PMID: 30282024

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Project description:Commissural interneurons (CINs) mediate interactions between rhythm-generating locomotor circuits located on each side of the spinal cord and are necessary for left-right limb coordination during locomotion. While glutamatergic V3 CINs have been implicated in left-right coordination, their functional connectivity remains elusive. Here, we addressed this issue by combining experimental and modeling approaches. We employed Sim1Cre/+; Ai32 mice, in which light-activated Channelrhodopsin-2 was selectively expressed in V3 interneurons. Fictive locomotor activity was evoked by NMDA and 5-HT in the isolated neonatal lumbar spinal cord. Flexor and extensor activities were recorded from left and right L2 and L5 ventral roots, respectively. Bilateral photoactivation of V3 interneurons increased the duration of extensor bursts resulting in a slowed down on-going rhythm. At high light intensities, extensor activity could become sustained. When light stimulation was shifted toward one side of the cord, the duration of extensor bursts still increased on both sides, but these changes were more pronounced on the contralateral side than on the ipsilateral side. Additional bursts appeared on the ipsilateral side not seen on the contralateral side. Further increase of the stimulation could suppress the contralateral oscillations by switching to a sustained extensor activity, while the ipsilateral rhythmic activity remained. To delineate the function of V3 interneurons and their connectivity, we developed a computational model of the spinal circuits consisting of two (left and right) rhythm generators (RGs) interacting via V0V, V0D, and V3 CINs. Both types of V0 CINs provided mutual inhibition between the left and right flexor RG centers and promoted left-right alternation. V3 CINs mediated mutual excitation between the left and right extensor RG centers. These interactions allowed the model to reproduce our current experimental data, while being consistent with previous data concerning the role of V0V and V0D CINs in securing left-right alternation and the changes in left-right coordination following their selective removal. We suggest that V3 CINs provide mutual excitation between the spinal neurons involved in the control of left and right extensor activity, which may promote left-right synchronization during locomotion.

Dataset Information

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits.

Publications

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits.

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