Although axonal GABAA receptors are thought to cause presynaptic inhibition, we show that instead they often facilitate sodium channel activation at nodes of myelinated axons. This facilitation determines which branches of sensory axons conduct action potentials to motor neurons, enabling computation at the level of the node to regulate sensory feedback.
This is a preview of subscription content, access via your institution
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Eccles, J. C., Eccles, R. M. & Magni, F. Central inhibitory action attributable to presynaptic depolarization produced by muscle afferent volleys. J. Physiol. 159, 147–166 (1961). This paper proposes the classic idea that presynaptic inhibition may be caused by primary afferent depolarization, which was later associated with GABAA receptors.
Lucas-Osma, A. M. et al. Extrasynaptic alpha5GABAA receptors on proprioceptive afferents produce a tonic depolarization that modulates sodium channel function in the rat spinal cord. J. Neurophysiol. 120, 2953–2974 (2018). This paper reports that GABAA receptors are not always at sensory axon terminals and do not depolarize terminals.
Henneman, E. The size-principle: a deterministic output emerges from a set of probabilistic connections. J. Exp. Biol. 115, 105–112 (1985). This classic paper where Henneman discusses the size principle of motor neuron recruitment also argues that sensory axons often fail to conduct spikes to motor neurons.
Wall, P.D. in Presynaptic Inhibition and Neuron Control 228–241 (Oxford Univ. Press, 1998). This review article discusses the seminal work of Wall on gating pain and spike propagation failure in sensory axons.
Goldstein, S. S. & Rall, W. Changes of action potential shape and velocity for changing core conductor geometry. Biophys. J. 14, 731–757 (1974). This pioneering computational paper by Wilfrid Rall discusses the mathematics of branch point failure.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Hari, K. et al. GABA facilitates spike propagation through branch points of sensory axons in the spinal cord. Nat. Neurosci. https://doi.org/10.1038/s41593-022-01162-x (2022).
About this article
Cite this article
GABA receptors near sodium channels facilitate spike propagation in myelinated axons. Nat Neurosci 25, 1253–1254 (2022). https://doi.org/10.1038/s41593-022-01163-w