Dataset Information

Neuronal Ig/Caspr recognition promotes the formation of axoaxonic synapses in mouse spinal cord.

ABSTRACT: Inhibitory microcircuits are wired with a precision that underlies their complex regulatory roles in neural information processing. In the spinal cord, one specialized class of GABAergic interneurons (GABApre) mediates presynaptic inhibitory control of sensory-motor synapses. The synaptic targeting of these GABAergic neurons exhibits an absolute dependence on proprioceptive sensory terminals, yet the molecular underpinnings of this specialized axoaxonic organization remain unclear. Here, we show that sensory expression of an NB2 (Contactin5)/Caspr4 coreceptor complex, together with spinal interneuron expression of NrCAM/CHL1, directs the high-density accumulation of GABAergic boutons on sensory terminals. Moreover, genetic elimination of NB2 results in a disproportionate stripping of inhibitory boutons from high-density GABApre-sensory synapses, suggesting that the preterminal axons of GABApre neurons compete for access to individual sensory terminals. Our findings define a recognition complex that contributes to the assembly and organization of a specialized GABAergic microcircuit.

SUBMITTER: Ashrafi S

PROVIDER: S-EPMC3898991 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Publications

Neuronal Ig/Caspr recognition promotes the formation of axoaxonic synapses in mouse spinal cord.

Ashrafi Soha S Betley J Nicholas JN Comer John D JD Brenner-Morton Susan S Bar Vered V Shimoda Yasushi Y Watanabe Kazutada K Peles Elior E Jessell Thomas M TM Kaltschmidt Julia A JA

Neuron 20140101 1

Inhibitory microcircuits are wired with a precision that underlies their complex regulatory roles in neural information processing. In the spinal cord, one specialized class of GABAergic interneurons (GABApre) mediates presynaptic inhibitory control of sensory-motor synapses. The synaptic targeting of these GABAergic neurons exhibits an absolute dependence on proprioceptive sensory terminals, yet the molecular underpinnings of this specialized axoaxonic organization remain unclear. Here, we show ...[more]

PMID: 24411736

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Project description:Rehabilitative exercise in humans with spinal cord injury aims to engage residual neural networks to improve functional recovery. We hypothesized that exercise combined with non-invasive stimulation targeting spinal synapses further promotes functional recovery. Twenty-five individuals with chronic incomplete cervical, thoracic, and lumbar spinal cord injury were randomly assigned to 10 sessions of exercise combined with paired corticospinal-motor neuronal stimulation (PCMS) or sham-PCMS. In an additional experiment, we tested the effect of PCMS without exercise in 13 individuals with spinal cord injury with similar characteristics. During PCMS, 180 pairs of stimuli were timed to have corticospinal volleys evoked by transcranial magnetic stimulation over the primary motor cortex arrive at corticospinal-motor neuronal synapses of upper- or lower-limb muscles (depending on the injury level), 1-2 ms before antidromic potentials were elicited in motor neurons by electrical stimulation of a peripheral nerve. Participants exercised for 45 min after all protocols. We found that the time to complete subcomponents of the Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) and the 10-m walk test decreased on average by 20% after all protocols. However, the amplitude of corticospinal responses elicited by transcranial magnetic stimulation and the magnitude of maximal voluntary contractions in targeted muscles increased on overage by 40-50% after PCMS combined or not with exercise but not after sham-PCMS combined with exercise. Notably, behavioural and physiological effects were preserved 6 months after the intervention in the group receiving exercise with PCMS but not in the group receiving exercise combined with sham-PCMS, suggesting that the stimulation contributed to preserve exercise gains. Our findings indicate that targeted non-invasive stimulation of spinal synapses might represent an effective strategy to facilitate exercise-mediated recovery in humans with different degrees of paralysis and levels of spinal cord injury.

Dataset Information

Neuronal Ig/Caspr recognition promotes the formation of axoaxonic synapses in mouse spinal cord.

Publications

Neuronal Ig/Caspr recognition promotes the formation of axoaxonic synapses in mouse spinal cord.

Similar Datasets

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