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bioRxiv · 10.1101/2022.07.04.498712

Locomotor-related propriospinal V3 neurons produce primary afferent depolarization and modulate sensory transmission to motoneurons

Lin, S.·Hari, K.·Lucas-Osma, A.·Black, S.·Khatmi, A.·Fouad, K.·Gorassini, M.·Li, Y.·Fenrich, K.·Bennett, D. J.
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Abstract

When a muscle is stretched it not only responds with a reflex, but the sensory afferent feedback also depolarizes many afferents throughout the spinal cord (termed primary afferent depolarization, PAD), readying the whole limb for further disturbances. This sensory-evoked PAD is thought to be caused by a trisynaptic circuit, where sensory input activates first order excitatory neurons that activate GABAergic neurons that in turn activate GABAA receptors on afferents to cause PAD, though the identity of these first order neurons is unclear. Here we show that these first order neurons are propriospinal V3 neurons, since they receive extensive sensory input and in turn innervate GABAergic neurons that cause PAD, because optogenetic activation or inhibition of V3 neurons in mice mimics or inhibits sensory-evoked PAD, respectively. Furthermore, persistent inward sodium currents (Na PICs) intrinsic to V3 neurons enable them to respond to transient inputs with long-lasting responses, explaining the long time-course of PAD. Also, local optogenetic activation of V3 neurons at one segment causes PAD in other segments, due to the long propriospinal tracts of these neurons, explaining the widespread radiation of PAD across the spinal cord. This in turn facilitates monosynaptic reflex transmission to motoneurons across the spinal cord. Additionally, we find that V3 neurons directly innervate proprioceptive afferents, causing a glutamate receptor mediated PAD (glutamate PAD). Finally, we show that increasing the spinal cord excitability with either GABAA receptor blockers or chronic spinal cord injury causes an increase in the glutamate PAD, perhaps contributing to spasms after SCI. Overall, we show the V3 neuron has a prominent role in modulating sensory transmission, in addition to its previously described role in locomotion.

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Lin, S., Hari, K., Lucas-Osma, A., Black, S., Khatmi, A., Fouad, K., Gorassini, M., Li, Y., Fenrich, K., Bennett, D. J.. 2022-07-05. Locomotor-related propriospinal V3 neurons produce primary afferent depolarization and modulate sensory transmission to motoneurons. https://doi.org/10.1101/2022.07.04.498712

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