Dendrite-Derived Supernumerary Axons on Adult Axotomized Motor Neurons Possess Proteins That Are Essential for the Initiation and Propagation of Action Potentials and Synaptic Vesicle Release

Abstract

Axotomy can trigger profound alterations in the neuronal polarity of adult neurons in vivo. This can manifest itself in the development of new axon-like processes emanating from the tips of distal dendrites. Previously, these processes have been defined as axonal based on their axonal morphology. This study extends this definition to determine whether, more importantly, these processes possess the prerequisite molecular machinery to function as axons. Using a combination of intracellular labeling and immunohistochemistry, we demonstrate that the distribution of voltage-gated sodium channels on these processes matches the arrangement of these channels that is necessary for the initiation and conduction of action potentials. At terminal bouton-like structures they possess key proteins necessary for the release of synaptic vesicles (SV2 and synaptophysin). Thus, axon-like processes emanating from the tips of distal dendrites represent a rearrangement of neuronal polarity whereby axotomized neurons can develop additional functional axons in vivo.

Spinal circuits for motor learning

“…This imbalance may also be present in spinal muscular atrophy, in which there is a reduction of Ia afferent input to MNs [54]. In both of these instances, changes in MN ion channel expression and excitability have been reported [54][55][56]. In fact, changes to MN properties can occur fairly rapidly following block of neuromuscular transmission, which would result in a mismatch between feed forward and feedback inputs [57].…”

Axons emanating from dendrites: phylogenetic repercussions with Cajalian hues

“…Dendrite-derived axons (“dendraxons”) were reported after axotomy in α -motoneurons of cat spinal cord (level L7) (Lindå et al, 1985 ). Novel “dendrite-derived supernumerary axons” can be functional, as suggested by voltage-gated Na + channel distribution and synaptophysin and glycoprotein SV2 expression, molecular prerequisites for AP propagation and neurotransmitter release (Meehan et al, 2011 ). Axotomized spinal commissural interneurons (level C3) also form de novo axon-like processes from distal or proximal dendrites or from the original axonal pole (Fenrich et al, 2007 ).…”

Retrograde response in axotomized motoneurons: Nitric oxide as a key player in triggering reversion toward a dedifferentiated phenotype

“…Concomitant with their changes in expression and composition, voltage-gated sodium channels are spatially redistributed to adopt aberrant locations on the dendritic membrane, which gives rise to the appearance of anomalous dendritic electrogenesis (Eccles et al, 1958;Kuno and Llina´s, 1970b;Sernagor et al, 1986). Targeting of sodium channels to the dendritic membrane could indicate the beginning of a change in neuronal polarity, since permanently axotomized motoneurons may develop new processes emanating from the tips of distal dendrites with molecular and structural characteristics that most closely resemble axons (Rose et al, 2001;Meehan et al, 2011). Peripheral nerve injury also induces declustering of somato-dendritic voltage-gated potassium channels (Kv2.1), which under normal conditions are locally aggregated at specific post-synaptic sites in motoneurons (Romer et al, 2014).…”