Analysis of the processes of summation of postsynaptic potentials on the membrane of motoneurons upon realization of the stretch reflex

Stretching of the m. triceps surae (TS) of decerebrated cats evokes reflex shifts of the membrane potential (MP) in spinal motoneurons resulting from summation of EPSPs. We carried out model analysis of summation of a great number of EPSPs and compared the respective results with changes in the MP observed in real experiments using intrasomatic microelectrode recording. Simulation was based on the supposition of the proximity of the time course of an excitatory postsynaptic current to the positive part of the EPSP derivative. Transformation of EPSPs was performed using low-frequency filtration with two values of the time constant, 7 and 20 msec, (models M1 and M2, respectively). The models obtained provided sufficiently adequate reflection of the ascending phase of the real EPSP but inadequately reflected the rate of its decline and slow components of the MP changes. The disagreement of simulations with the real MP shifts shows that, most probably, final postsynaptic effects are to a considerable extent provided by summation of a great number of EPSPs generated in distal dendrites, and EPSPs immediately recorded in trasomatically cannot provide one with adequate information on the entire pattern of natural synaptic activation of the neuron. In addition, simulation analysis demonstrated a high probability of the contribution of active inhibitory processes to the formation of resulting MP changes under conditions of the stretch reflex. Neirofiziologiya/Neurophysiology, Vol. 40, No. 3, pp. 260–263, May–June, 2008.     

Loss of information on central summation of local postsynaptic potentials

The spatio-temporal pattern of spikes converging on a neuron and variations in the combined depolarizing potential in the trigger zone are regarded as information carriers. In both cases the quantity of information is calculated; it is assumed that the depolarizing potential is formed as the weighted sum of the local PSPs. It is concluded from a comparison of the results that "algebraic" summation of PSPs is accompained by loss of essential information, and information carried by variation in the combined PSP is generated only by unessential input information. The investigation confirms the important role of a high spatial damping constant of electrotonic potentials in the dendrites. The damping prevents annihilation of much of the information. Electrical action of "effective" synapses on the trigger zone must evidently be regarded as sensitivity control, with no effect on the information content of the process but capable of weakening or interrupting the transmission of information from dendrites to the trigger zone. It is concluded that the combined PSP cannot serve as an information carrier and that this function may perhaps be performed by signals of a different physical nature which do not undergo damping in the dendrites.M. I. Kalinin Leningrad Polytechnical Institute. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 186–192, March–April, 1973.     

Changes in membrane potential and postsynaptic potentials evoked by strychnine in neocortical neurons

Intracellular responses of neurons of the suprasylvian fissure to intracortical stimulation before and during topical cortical strychnine application was studied in experiments on immobilized, unanesthetized cats (a local anesthetic was used). Untreated cortical neurons responded to intracortical stimulation with a monosynaptic excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). Application of strychnine evoked epileptiform population activity and paroxysmal depolarizations of neuronal membrane potentials (MPs), followed by hyperpolarization. Increased hyperpolarizations, and the prolonged duration of their summation were responsible for an increased MP and reduced or abolished tonic spike activity. Intracellular application (as a result of diffusion from the microelectrode) of ethyleneglycoltetraacetate (EGTA) that blocked the calcium-dependent potassium membrane conductance (gK(Ca)) abolished the hyperpolarization. The development of epileptiform activity was accompanied by reduction of the IPSP, and an increase in the monosynaptic EPSP. The role of gK(Ca) and postsynaptic inhibition in epileptogenesis is discussed.I. I. Mechnikov State University, Odessa. Translated from Neirofiziologiya, Vol. 24, No. 6, pp. 684–691, November–December, 1992.     

Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell

The rules of synaptic integration in pyramidal cells remain obscure, in part due to conflicting interpretations of existing experimental data. To clarify issues, we developed a CA1 pyramidal cell model calibrated with a broad spectrum of in vitro data. Using simultaneous dendritic and somatic recordings and combining results for two different response measures (peak versus mean EPSP), two different stimulus formats (single shock versus 50 Hz trains), and two different spatial integration conditions (within versus between-branch summation), we found that the cell's subthreshold responses to paired inputs are best described as a sum of nonlinear subunit responses, where the subunits correspond to different dendritic branches. In addition to suggesting a new type of experiment and providing testable predictions, our model shows how conclusions regarding synaptic arithmetic can be influenced by an array of seemingly innocuous experimental design choices.     

Excitatory postsynaptic potentials in the mammalian central nervous system associated with an increase in the membrane resistance

The effects of stimulations of the rat habenulo-interpeduncular pathway on the membrane potentials and conductance changes in the interpeduncular neurones were examined in an $\text{in}$$\text{vitro}$ slice preparation. Low frequency stimulations produced short latency conventional type excitatory postsynaptic potentials (EPSPs). When the pathway was stimulated at higher frequencies, however, a slow and prolonged EPSP could be elicited. Both the slow and the fast EPSPs were abolished by the removal of calcium and the addition of manganese to the perfusion solution, indicating that they were produced by the release of a chemical transmitter. The slow, but not the fast EPSP, appears to be associated with an increase in the membrane resistance.     

Upper and lower bounds on the non-linearity of sommation of end-plate potentials

The amplitudes of end-plate potentials are non-linearly related to the number of transmitter packets eliciting the potentials. The form of the non-linearity depends on the time-course of the change in membrane conductance as compared with the membrane time-constant. Approximate solutions for very short and very long time-constants provide upper and lower bounds on the relationship between the peak amplitude of the end-plate potential and the relative number of transmitter packets.     

Determinants of postsynaptic Ca2+ signaling in Purkinje neurons

Neuronal integration in Purkinje neurons involves many forms of Ca2+ signaling. Two afferent synaptic inputs, the parallel and the climbing fibers, provide a major drive for these signals. These two excitatory synaptic inputs are both glutamatergic. Postsynaptically they activate alpha-amino-3-hydroxy-5-methyl-4-propionic acid (AMPA) receptors (AMPARs) and metabotropic glutamate receptors (mGluRs). Unlike most other types of central neurons, Purkinje neurons do not express NMDA (N-methyl-D-aspartate) receptors (NMDARs). AMPARs in Purkinje neurons are characterized by a low permeability for Ca2+ ions. AMPAR-mediated synaptic depolarization may activate voltage-gated Ca2+ channels, mostly of the P/Q-type. The resulting intracellular Ca2+ signals are shaped by the Ca2+ buffers calbindin and parvalbumin. Ca2+ clearance from the cytosol is brought about by Ca2+-ATPases in the plasma membrane and the endoplasmic reticulum, as well as the Na+-Ca2+-exchanger. Binding of glutamate to mGluRs induces postsynaptic Ca2+-transients through two G protein-dependent pathways: involving (1) the release of Ca2+ ions from intracellular Ca2+ stores and (2) the opening of the cation channel TRPC1. Homer proteins appear to play an important role in postsynaptic Ca2+ signaling by providing a direct link between the plasma membrane-resident elements (mGluRs and TRPC1) and their intracellular partners, including the IP3Rs.     

Simultaneous imaging of cell and mitochondrial membrane potentials.

The distribution of charged membrane-permeable molecular probes between intracellular organelles, the cytoplasm, and the outside medium is governed by the relative membrane electrical potentials of these regions through coupled equilibria described by the Nernst equation. A series of highly fluorescent cationic dyes of low membrane binding and toxicity (Ehrenberg, B., V. Montana, M.-D. Wei, J. P. Wuskell, and L. M. Loew, 1988. Biophys. J. 53:785-794) allows the monitoring of these equilibria through digital imaging video microscopy. We employ this combination of technologies to assess, simultaneously, the membrane potentials of cells and of their organelles in situ. We describe the methodology and optimal conditions for such measurements, and apply the technique to concomitantly follow, with good time resolution, the mitochondrial and plasma membrane potentials in several cultured cell lines. The time course of variations induced by chemical agents (ionophores, uncouplers, electron transport, and energy transfer inhibitors) in either or both these potentials is easily quantitated, and in accordance with mechanistic expectations. The methodology should therefore be applicable to the study of more subtle and specific, biologically induced potential changes in cells.     

Effect of non-linearity in predicting doppler waveforms through a novel model

Background  

In pregnancy, the uteroplacental vascular system develops de novo locally in utero and a systemic haemodynamic & bio-rheological alteration accompany it. Any abnormality in the non-linear vascular system is believed to trigger the onset of serious morbid conditions like pre-eclampsia and/or intrauterine growth restriction (IUGR). Exact Aetiopathogenesis is unknown. Advancement in the field of non-invasive doppler image analysis and simulation incorporating non-linearities may unfold the complexities associated with the inaccessible uteroplacental vessels. Earlier modeling approaches approximate it as a linear system.     

Computer simulation of model lipid membrane dynamics

The motions of individual lipid molecules in a model membrane have been studied by computer simulation using the molecular dynamics technique. The intermolecular forces were of both the Lennard-Jones and the Coulomb type. The influence of temperature and electrical screening on the order-disorder transition was examined, and it was also found that this transition is initiated by the spontaneous generation of disclinations.     

Elementary and compound postsynaptic potentials in the defensive command neurons of Helix lucorum

The present communication concerns with the analysis of elementary and the compound excitatory postsynaptic potentials (eEPSPs and cEPSPs) recorded by intracellular microelectrode from an identified defensive command neuron of the snail Helix lucorum. The eEPSPs were evoked by single presynaptic action potentials (APs) elicited by cationic current injection into one of the identified sensory neurons synapsing on the respective command neuron. The cEPSPs were elicited by local brief tactile stimuli on the skin or internal organs. It was shown that the cEPSPs amplitudes depend mainly on the number of activated sensory neurons. Compound EPSPs depend also on frequency and the number of APs in the bursts occurring in a single neuron. Presynaptic APs having frequency 2-10 Hz evoke high frequency depression of that eEPSPs after an interval is followed by post-tetanic potentiation of single eEPSPs. Preceding stimulation of a pneumostom area facilitates the cEPSPs elicited by repeated stimulation of viscera. The eEPSPs from the same visceral area demonstrate no heterosynaptic facilitation in experiments with double parallel intracellular recording from responsive sensory and command neurons. The different types of the eEPSPs plasticity are discussed according to their contribution cEPSPs plastic changes.     

The structure of a model membrane in relation to the viscoelastic properties of the red cell membrane

The molecular arrangement within a lamellar structure composed of human erythrocyte lipids is determined. The 45 A thick lipid layer, in water, is filled in the interior with a liquid-like configuration of the hydrocarbon chains of phospholipid molecules and is covered on both sides by their hydrophilic polar groups. Cholesterol is located so that part of its steroid nucleus is between the polar groups of the phospholipid molecules while the rest of the molecule extends into the inner hydrocarbon layer. This lipid leaflet would be expected to have the mechanical properties of a purely liquid surface, as other authors have shown for the "black" lipid membranes. Data are presented which demonstrate that the intact erythrocyte membrane is a tough viscoelastic substance with a Young''s modulus of 10⁶–10⁸ dynes/cm² and a viscosity of 10⁷–10¹⁰ poises. The parameters and the kinetics of membrane breakdown are incompatible with the model system of pure lipid. Caution must be exercised in applying various data on the model systems to intact membranes.