Subtle re-location of dendritic spine branches containing membrane with fast spiking mechanisms can alter synaptic efficacy

The potential physiological impact of morphological changes in the active dendritic spines, which are believed to be associated with altered synaptic efficacy, was investigated in a computer simulation study using the NEURON package [1]. A compartmental model of a simplified neuron was built, which included 30 complex spines (neck, head, and active zone) and accommodating AMPA-type synaptic inputs with alpha-function conductances. Hodgkin-Huxley type excitable membranes were inserted into the spine heads. It was shown that arranging spines in dense clusters, as opposed to a uniformly random spine distribution, has a negligible effect on the synaptic signal transfer (other model conditions, including synaptic input and spine density, remained unchanged). However, if a proportion (e.g., 3–20%) of the spines partly fuse with their neighbors forming branched spines, this could increase dramatically the cell response to the unchanged synaptic input. Results of this pilot study provide the basis for a more detailed investigation of the relationship between the spine arrangement and synaptic function, considering dual-component synaptic currents and mechanisms controlling ion fluxes in the dendritic compartments.     

Role of the Plasma Membrane Ca2+-ATPase Pump in the Regulation of Rhythm Generation by an Interstitial Cell of Cajal: A Computational Study

Neurophysiology - Gastrointestinal motility is based on the rhythmic activity of interstitial cells of Cajal (ICCs). The ICC rhythm generation relies upon characteristic Ca2+-handling mechanisms...     

Heterogeneous synaptic covering and differential charge transfer sensitivity among the dendrites of a reconstructed abducens motor neurone: Correlations between electron microscopic and computer simulation data

Ultrastructural studies on the synaptology of dendritic arborizations of motoneurones have been problematic because dendrites are very thin in relation to their great length, and most of the studies on this topic have therefore dealt with only small parts of the dendritic tree. Here we compared the ultrastructural characteristics of the axon terminals distributed along the various dendrites of a single motoneurone. For this purpose, the light microscopic 3D reconstruction of the dendritic arborization of an intracellularly labelled abducens motoneurone was combined with an electron microscopic analysis of its synaptic contacts. Dendritic profiles were randomly sampled along the various dendrites and the axon terminals they received were classified on the basis of their ultrastructural features and their GABA-immunoreactivity. It emerged that the various dendrites differed according to the type and local arrangement of their synaptic inputs. Our second aim was to incorporate the morphological data obtained into a model giving the charge transfer effectiveness T(x) of the dendritic sites. The sensitivity S(x) of T(x) to changes in the membrane resistivity (Rm) simulating various levels of tonic synaptic activity was calculated. It turned out that both the proximal and distal regions of the dendritic arborization have a dense synaptic covering and a weak sensitivity to changes in the Rm, whereas the intermediate dendrites have a sparse synaptic covering and a high sensitivity to changes in tonic synaptic activity. This pattern of organisation might mediate the “gating” of a population of synapses covering some dendritic regions in a state-dependent fashion.     

Distribution of Cell Adhesion Molecules (CAM) along the Branching Neurite Surface: Model-Inherited Effects of the Branch Diameters and Mode of CAM Transport

In many cases, an increase in the surface density of cell adhesion molecules (CAM) in the distal parts of a growing neurite is favorable for the neurite elongation. This increase is attained by exocytotic insertion of CAM-containing vesicles into the growth cones with subsequent redistribution of CAM along the cell surface due to lateral diffusion and endocytosis. Using a mathematical model describing these processes, we quantitatively describe conditions providing two qualitatively different profiles in a branching neurite: (i) the CAM surface density increases along both daughter branches, which would be in favor of further outgrowth of both branches, i.e., successful branching, or (ii) the CAM surface density increases along one daughter branch and decreases along another branch, which could lead to the retraction of the latter. The geometric factors and mechanisms underlying the intracellular CAM transport to the daughter growth cones were proved to determine the profile of CAM surface density. A similarity in the diameters of daughter branches, their short lengths, a high value of the lateral transfer constant, and partitioning of CAM transport at the branching point proportionally to the surface areas of daughter branches are in favor of an increase in the CAM surface density along both daughter branches. Asymmetric branching can lead to a decrease in the CAM surface density along the thinner or thicker daughter branch, if CAM trafficking was equally partitioned or was proportional to the branch cross-sectional areas, respectively. The proposed model helps to understand possible relationships between the intracellular CAM trafficking, CAM surface distribution, and geometry of branching of the neurites.     

Electrical bistability in a neuron model with monostable dendritic and axosomatic membranes

In a two-compartment mathematical model, we studied the reason for and conditions of manifestation of electrical bistability in a neuron composed of monostable parts. One compartment of the model simulated the dendrites; their membrane was monostable at high depolarization and characterized by an N-shaped steady current-voltage (I–V) characteristic endowed by inward synaptic current through voltage-dependent channels sensitive to N-methyl-D-aspartate (NMDA). Another compartment simulated the axosomatic region with a positively sloped linearizedI–V characteristic of the membrane monostable at the resting membrane potential. For the whole cell, bistability was obvious at a subcritical intensity of NMDA activation; the reason was the current directed from the more depolarized dendritic region into the somatic region, and the necessary condition was that the above somatopetal core current must exceed the net inward transmembrane current (the latter was the sum of the inward synaptic and outward passive extrasynaptic currents) of the dendritic compartment. This relation essentially depended on the size of the dendrites. Neirofiziologiya/Neurophysiology, Vol. 32, No. 2, pp. 98–101, March–April, 2000.     

The electro-dynamics of the dendritic space in Purkinje cells of the cerebellum

The functional geometry of the reconstructed dendritic arborization of Purkinje neurons is the object of this work. The combined effects of the local geometry of the dendritic branches and of the membrane mechanisms are computed in passive configuration to obtain the electrotonic structure of the arborization. Steady-currents applied to the soma and expressed as a function of the path distance from the soma form different clusters of profiles in which dendritic branches are similar in voltages and current transfer effectiveness. The locations of the different clusters are mapped on the dendrograms and 3D representations of the arborization. It reveals the presence of different spatial dendritic sectors clearly separated in 3D space that shape the arborization in ordered electrical domains, each with similar passive charge transfer efficiencies. Further simulations are performed in active configuration with a realistic cocktail of conductances to find out whether similar spatial domains found in the passive model also characterize the active dendritic arborization. During tonic activation of excitatory synaptic inputs homogeneously distributed over the whole arborization, the Purkinje cell generates regular oscillatory potentials. The temporal patterns of the electrical oscillations induce similar spatial sectors in the arborization as those observed in the passive electrotonic structure. By taking a video of the dendritic maps of the membrane potentials during a single oscillation, we demonstrate that the functional dendritic field of a Purkinje neuron displays dynamic changes which occur in the spatial distribution of membrane potentials in the course of the oscillation. We conclude that the branching pattern of the arborization explains such continuous reconfiguration and discuss its functional implications.