Microgeometrical dendritic factors predict electrical decoupling between somatic and dendritic compartments in magnocellular neurosecretory neurons

Abstract

It is generally assumed that dendritic release of neuropeptides from magnocellular neurosecretory neurons (MNNs), a critical process involved in homeostatic functions, is an activity-dependent process that requires backpropagating action potentials (APs). Still, growing evidence indicates that dendritic release can occur in the absence of APs, and axonal APs have been shown to fail to evoke dendritic release. These inconsistencies strongly suggest that APs in MNNs may fail to backpropagating into dendrites. Here we tested whether simple factors of electrical signal attenuation could lead to effective decoupling between cell's body and dendritic release site within typical geometrical characteristics of MNN. We developed a family of linear mathematical models of MNNs and evaluated whether the somato-dendritic transfer of electrical signals is influenced by the geometrical characteristics. We determined the prerequisites for critically strong dendritic attenuation of the somatic input which are sufficient to explain the failure of APs initiated in the soma to backpropagating into dendritic compartments. Being measured in 100 μm from soma voltage attenuations down to 0.1 and 0.01 of the input value were chosen as the markers of electrical decoupling of dendritic sites from the soma, considering 0.1 insufficient for triggering dendritic spikes and 0.01 indistinguishable from background noise. The tested micro-geometrical factors were the dendritic stem diameter, varicosities, and size of peri-dendritic space limited by glial sheath wrapping. Varicosities increased the attenuation along homogeneous proximal dendrites by providing an increased current leak at the junction with the proximal dendritic section. The glial sheath wrapping a dendrite section promoted greater attenuation by increasing longitudinal resistance of the interstitial peri-dendritic space thus playing the insulating role. These decoupling effects were strengthened in the case of the dendritic stems with thinner diameters of and/or increased conductivity of the membrane. These micro-geometrical factors are biophysically realistic and predict electrical decoupling between somatic and dendritic compartments in MNNs.

Keywords: dendritic release; dendritic voltage attenuation; electro-geometrical (de)coupling; glial sheath wrapping; peri-dendritic space; varicosity.