Myelination Increases the Spatial Extent of Analog-Digital Modulation of Synaptic Transmission: A Modeling Study

Abstract

Analog-digital facilitations (ADFs) have been described in local excitatory brain circuits and correspond to a class of phenomena describing how subthreshold variations of the presynaptic membrane potential influence spike-evoked synaptic transmission. In many brain circuits, ADFs rely on the propagation of somatic membrane potential fluctuations to the presynaptic bouton where they modulate ion channels availability, inducing modifications of the presynaptic spike waveform, the spike-evoked Ca 2+ entry, and the transmitter release. Therefore, one major requirement for ADFs to occur is the propagation of subthreshold membrane potential variations from the soma to the presynaptic bouton. To date, reported ADFs space constants are relatively short (250-500 µm) which limits their action to proximal synapses. However, ADFs have been studied either in unmyelinated axons or in juvenile animals in which myelination is incomplete. We examined here the potential gain of ADFs spatial extent caused by myelination using a realistic model of L5 pyramidal cell. Myelination of the axon was found to induce a 3-fold increase in the axonal length constant. As a result, the different forms of ADF were found to display a much longer spatial extent (up to 3,000 µm). In addition, while the internodal length displayed a mild effect, the number of myelin wraps ensheathing the internodes was found to play a critical role in the ADFs spatial extents. We conclude that axonal myelination induces an increase in ADFs spatial extent in our model, thus making ADFs plausible in long-distance connections.

Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry

“…estimated ~9 mV depolarization in a presynaptic bouton led to a 37% increase in synaptic transmission for a single AP [60]. Extrapolating from the peak axon polarizations in this study would suggest tDCS could produce up to ~4% facilitation in L2/3 PCs and ~1% facilitation in L4 LBCs axon terminals.…”

Multi-scale model of axonal and dendritic polarization by transcranial direct current stimulation in realistic head geometry

“…Indeed, Chakraborty et al found changes in action potential waveform properties in the axon bleb, but not soma, with 5 V/m uniform E-field stimulation [ 21 ]. In a computational model reproducing depolarization and hyperpolarization facilitation of synaptic transmission, Zbili et al estimated ~9 mV depolarization in a presynaptic bouton led to a 37 % increase in synaptic transmission for a single AP [ 67 ]. Extrapolating from the peak axon polarizations in this study would suggest tDCS could produce up to ~4 % facilitation in L2/3 PCs and ~1 % facilitation in L4 LBCs axon terminals.…”

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons

“…The delayed rectifier in the previously cited models was replaced by separate models of K v 1 and K v 2 currents known to be present in CA1 pyramidal cells (Kirizs et al, 2014; Liu and Bean, 2014; Morgan et al, 2019). The K v 1 model was taken from Zbili and Debanne (2020) and the K v 2 model from https://senselab.med.yale.edu/ModelDB/showModel?model=184176. An inward rectifying potassium channel I KIR was also added, consistent with the literature (Chen and Johnston, 2005): .…”