Biology subjects

Fenrich, K. K.

Publications and source records attributed to Fenrich, K. K..

3 recordsLinked to original sources

bioRxiv2026

Activity-dependent structural plasticity of myelinated axons tunes their excitability

Myelinated axons are classically viewed as stable cables of fixed geometry. We show here that a brief subthreshold stimulation of single nodes in mouse dorsal column axons drives a rapid, lasting structural change: the stimulated axons shrink locally along the internode segments adjacent to the node, to about 70% of their diameter within a few seconds, while neighbouring glia swell to fill the space, sparing the node, paranode and more distant internodes. The thinned axon becomes markedly more excitable for hours, by an amount cable theory predicts from its shorter internodal length constant rather than from active currents that tend to decay over long periods. Using a grease-gap signal that reports the axial-conductance change, we find the axon thinning requires under-myelin Kv1 channels, Na/K-ATPase pumps, bicarbonate, and altered pH, consistent with a regenerative periaxonal potassium build-up that osmotically compresses the axon and swells glia, as previously proposed for physiological high-frequency firing. We present evidence that this mechanism may contribute to the long-lasting clinical benefits of spinal cord stimulation. Axonal GABAA receptor activation reproduces and occludes the plasticity induced by stimulation, indicating that they share a common underlying mechanism. Activity-dependent axon thinning thus enables potent physiologically relevant long term control of conduction, with potential clinical applications.

neuroscience↗

bioRxiv2024

Widespread innervation of motoneurons by spinal V3 neurons globally amplifies locomotor output in mice.

While considerable progress has been made in understanding the neuronal circuits that underlie the patterning of locomotor behaviours such as walking, less is known about the circuits that amplify motoneuron output to enable adaptable increases in muscle force across different locomotor intensities. Here, we demonstrate that an excitatory propriospinal neuron population (V3 neurons, Sim1+) forms a large part of the total excitatory interneuron input to motoneurons ([~]20%) across all hindlimb muscles. Additionally, V3 neurons make extensive connections among themselves and with other excitatory premotor neurons (such as V2a neurons). These circuits allow local activation of V3 neurons at just one segment (via optogenetics) to rapidly depolarize and amplify locomotor-related motoneuron output at all lumbar segments in both the in vitro spinal cord and the awake adult mouse. Interestingly, despite similar innervation from V3 neurons to flexor and extensor motoneuron pools, functionally, V3 neurons exhibit a pronounced bias towards activating extensor muscles. Furthermore, the V3 neurons appear essential to extensor activity during locomotion because genetically silencing them leads to slower and weaker mice with a poor ability to increase force with locomotor intensity, without much change in the timing of locomotion. Overall, V3 neurons increase the excitability of motoneurons and premotor neurons, thereby serving as global command neurons that amplify the locomotion intensity.

neuroscience↗

bioRxiv2021

Nodal GABA facilitates axon spike transmission 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, facilitates sensory feedback to motoneurons in awake rodents and humans. GABAA receptors and GAD2+ innervation at or near nodes of Ranvier of sensory axons cause this facilitation, preventing spike propagation failure at the many axon branch points, which is otherwise common without GABA. In contrast, GABAA receptors are generally lacking from axon terminals (unlike GABAB) and do not presynaptically inhibit transmitter release onto motoneurons. 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 CNS axons.

neuroscience↗