GABA facilitates spike propagation through branch points of sensory axons in the spinal cord

Movement and posture depend on sensory feedback that is regulated by specialized GABAergic neurons (GAD2(+)) that form axo-axonic contacts onto myelinated proprioceptive sensory axons and are thought to be inhibitory. However, we report here that activating GAD2(+) neurons directly with optogenetics or indirectly by cutaneous stimulation actually facilitates sensory feedback to motor neurons in rodents and humans. GABA(A) receptors located at or near nodes of Ranvier of sensory axons cause this facilitation by preventing spike propagation failure at the many axon branch points, which is otherwise common without GABA. In contrast, GABA(A) receptors are generally lacking from axon terminals and so cannot inhibit transmitter release onto motor neurons, unlike GABA(B) receptors that cause presynaptic inhibition. GABAergic innervation near nodes and branch points allows individual branches to function autonomously, with GAD2(+) neurons regulating which branches conduct, adding a computational layer to the neuronal networks generating movement and likely generalizing to other central nervous system axons. This study shows that, rather than causing inhibition, axonal GABA(A) receptors often facilitate sodium channel activation and prevent spike propagation failure at branch points of myelinated spinal cord sensory neuron axons.

Automated summary

Activating GAD2(+) neurons facilitates sensory feedback to motor neurons instead of inhibiting it. GABA(A) receptors located at branch points of sensory axons prevent spike propagation failure and allow individual branches to function autonomously.