scholarly journals Inferring neuronal ionic conductances from membrane potentials using CNNs

2019 ◽  
Author(s):  
Roy Ben-Shalom ◽  
Jan Balewski ◽  
Anand Siththaranjan ◽  
Vyassa Baratham ◽  
Henry Kyoung ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Membrane Resistance ◽  
Neuronal Model ◽  
Membrane Potentials ◽  
Training Data ◽  
Neuronal Membrane ◽  
Neuron Models ◽  
Input Stimulus ◽  
Spatially Resolved ◽  
Ionic Conductances

AbstractThe neuron is the fundamental unit of computation in the nervous system, and different neuron types produce different temporal patterns of voltage fluctuations in response to input currents. Understanding the mechanism of single neuron firing patterns requires accurate knowledge of the spatial densities of diverse ion channels along the membrane. However, direct measurements of these microscopic variables are difficult to obtain experimentally. Alternatively, one can attempt to infer those microscopic variables from the membrane potential (a mesoscopic variable), or features thereof, which are more experimentally tractable. One approach in this direction is to infer the ionic densities as parameters of a neuronal model. Traditionally this is done using a Multi-Objective Optimization (MOO) method to minimize the differences between features extracted from a simulated neuron’s membrane potential and the same features extracted from target data. Here, we use Convolutional Neural Networks (CNNs) to directly regress generative parameters (e.g., ionic conductances, membrane resistance, etc.,) from simulated time-varying membrane potentials in response to an input stimulus. We simulated diverse neuron models of increasing complexity (Izikivich: 4 parameters; Hodgkin-Huxley: 7 parameters; Mainen-Sejnowski: 10 parameters) with a large range of variation in the underlying parameter values. We show that hyperparameter optimized CNNs can accurately infer the values of generative variables for these neuron models, and that these results far surpass the previous state-of-the-art method (MOO). We discuss the benefits of optimizing the CNN architecture, improvements in accuracy with additional training data, and some observed limitations. Based on these results, we propose that CNNs may be able to infer the spatial distribution of diverse ionic densities from spatially resolved measurements of neuronal membrane potentials (e.g. voltage imaging).

scholarly journals Electrophysiology of the Heart of an Isopod Crustacean: Porcellio Dilatatus

1972 ◽  
Vol 57 (3) ◽  
pp. 609-631
Author(s):  
J. C. DELALEU ◽  
A. BLONDEAU ◽  
A. HOLLEY
Keyword(s):  
Membrane Potential ◽  
Action Potentials ◽  
Additional Data ◽  
Ionic Currents ◽  
Membrane Resistance ◽  
Resting Membrane Potential ◽  
Plateau Phase ◽  
Bathing Medium ◽  
Ionic Conductances ◽  
Rate Of Decline

1. The effects of various ions and chemicals were tested on the resting or active membrane of the heart of the wood-louse Porcellio dilatatus. 2. The curve relating the resting membrane potential to log [K+]o was found to correspond with the theoretical curve expected from the Nernst equation at higher concentrations only. Excess K+ decreased both amplitude and rate of rise of the response while the rate of decline was increased. In K+-deficient solutions the duration of the plateau phase was at first increased, then depressed. The addition of K+ to a bathing medium deprived for several minutes of this ion caused a large increase in the membrane potential and in the response height. The way in which the membrane was seen to react was tentatively attributed to an electrogenic active pumping mechanism. 3. In Na+-deficient solutions, the rate of rise and the height of the response were reduced while the resting membrane potential was decreased. 4. Ca2+-deficient solutions depolarized the membrane and decreased both amplitude and duration of the response. Cessation of activity occurred in Ca2+-free solution. In excess calcium the membrane was hyperpolarized. The rhythm and the rate of rising were decreased and the plateau phase depressed. 5. TTX blocked the heart activity, probably by acting upon the heart ganglion. Mn2+ depressed especially the humped plateau (when present) of the spontaneous responses. 6. TEA, caffeine and procaine transformed spontaneous activity of weak amplitude into large and complex overshooting responses. In TEA solutions, several stable levels of polarization were observed. Contrary to what occurred in the normal solution, depolarizing current pulses could trigger large all-or-none action potentials when TEA was present. 7. The TEA-induced regenerative response was analysed with the help of an intracellular stimulating current when [Na+]o and [Ca2+]o were varied. Additional data were obtained by applying TTX, Mn2+ or GABA. From the results, both Ca2+ and Na+ were thought to be involved in the ionic currents underlying spike type activity. 8. The spike-generating effect of TEA has been attributed to its property of increasing the membrane resistance and of allowing the ionic conductances which generate the weakly active component of the normal response, the plateau, but not the initial upstroke, to be amplified regeneratively. 9. The large spikes elicited by TEA were found relatively less effective than weak sustained depolarization in inducing strong contractions. 10. The functional significance of the data was tentatively interpreted by comparison with the properties of the heart of Limulus, Crustacea and vertebrates.

The Neuron at Rest

2017 ◽  
Author(s):  
Peggy Mason
Keyword(s):  
Membrane Potential ◽  
Ion Channels ◽  
Ionic Species ◽  
Membrane Resistance ◽  
Chloride Ions ◽  
Resting Membrane Potential ◽  
Neuronal Membrane ◽  
Nernst Potential ◽  
State Potential ◽  
Pass Through

Neuronal membrane potential depends on the distribution of ions across the plasma membrane and the permeability of the membrane to those ions afforded by transmembrane proteins. Ions cannot pass through a lipid bilayer but enter or exit neurons through ion channels. When activated by voltage or a ligand, ion channels open to form a pore through which selective ions can pass. The ion channels that support a resting membrane potential are critical to setting a cell’s excitability. From the distribution of an ionic species, the Nernst potential can be used to predict the steady-state potential for that one ion. Neurons are permeable to potassium, sodium, and chloride ions at rest. The Goldman-Hodgkin-Katz equation takes into consideration the influence of multiple ionic species and can be used to predict neuronal membrane potential. Finally, how synaptic inputs affect neurons through synaptic currents and changes in membrane resistance is described.

Estimation of Time-Dependent Input from Neuronal Membrane Potential

2011 ◽  
Vol 23 (12) ◽  
pp. 3070-3093 ◽  
Author(s):  
Ryota Kobayashi ◽  
Shigeru Shinomoto ◽  
Petr Lansky
Keyword(s):  
Membrane Potential ◽  
Empirical Bayes ◽  
Simulated Data ◽  
Time Dependent ◽  
Inhibitory Neurons ◽  
Likelihood Method ◽  
Neuronal Membrane ◽  
Neuron Models ◽  
Firing Rates ◽  
Mean And Variance

The set of firing rates of the presynaptic excitatory and inhibitory neurons constitutes the input signal to the postsynaptic neuron. Estimation of the time-varying input rates from intracellularly recorded membrane potential is investigated here. For that purpose, the membrane potential dynamics must be specified. We consider the Ornstein-Uhlenbeck stochastic process, one of the most common single-neuron models, with time-dependent mean and variance. Assuming the slow variation of these two moments, it is possible to formulate the estimation problem by using a state-space model. We develop an algorithm that estimates the paths of the mean and variance of the input current by using the empirical Bayes approach. Then the input firing rates are directly available from the moments. The proposed method is applied to three simulated data examples: constant signal, sinusoidally modulated signal, and constant signal with a jump. For the constant signal, the estimation performance of the method is comparable to that of the traditionally applied maximum likelihood method. Further, the proposed method accurately estimates both continuous and discontinuous time-variable signals. In the case of the signal with a jump, which does not satisfy the assumption of slow variability, the robustness of the method is verified. It can be concluded that the method provides reliable estimates of the total input firing rates, which are not experimentally measurable.

scholarly journals Estimation of the membrane potential of cultured macrophages from the fast potential transient upon microelectrode entry

1983 ◽  
Vol 96 (3) ◽  
pp. 796-801 ◽  
Author(s):  
C Ince ◽  
DL Ypey ◽  
R Van Furth ◽  
AA Verveen
Keyword(s):  
Membrane Potential ◽  
Single Cells ◽  
Membrane Resistance ◽  
Peritoneal Macrophages ◽  
Mean Value ◽  
Membrane Potentials ◽  
Isolated Cells ◽  
Real Value ◽  
Mouse Peritoneal Macrophages ◽  
Peak Value

Analysis of membrane potential recordings upon microelectrode impalement of four types of macrophages (cell lines P388D1 and PU5-1.8, cultured mouse peritoneal macrophages, and cultured human monocytes) reveals that these cells have membrane potentials at least two times more negative than sustained potential values (E(s)) frequently reported. Upon microelectrode entry into the cell (P388D1), the recorded potential drops to a peak value (E(p)) (mean -37 mV for 50 cells, range -15 to -70 mV) within 2 ms, after which it decays to a depolarized potential (E(n)) (mean -12 mV) in about 20 ms. Thereafter, the membrane develops one or a series of slow hyperpolarizations before a final sustained membrane potential (E(s)) (mean -14 mV, range -5 to -40) is established. The mean value of the peak of the first hyperpolarization (E(h)) is -30 mV (range -10 to -55 mV). The initial fast peak transient, measured upon microelectrode entry, was first described and analyzed by Lassen et al. (Lassen, U.V., A.M. T. Nielson, L. Pape, and L. O. Simonsen, 1971, J. Membr. Biol. 6:269-288 for other change in the membrane potential from its real value before impalement to a sustained depolarized value. This was shown to be true for macrophages by two-electrode impalements of single cells. Values of E(p), E(n), E(h), E(s), and membrane resistance (R(m)) measured for the other macrophages were similar to those of P388D1. From these results we conclude that E(p) is a better estimate of the true membrane potential of macrophages than E(s), and that the slow hyperpolarizations upon impalement should be regarded as transient repolarizations back to the original membrane potentials. Thus, analysis of the initial fast impalement transient can be a valuable aid in the estimation of the membrane potential of various sorts of small isolated cells by microelectrodes.

Consequences of 4-aminopyridine applications to trigeminal root ganglion neurons

1989 ◽  
Vol 62 (3) ◽  
pp. 810-820 ◽  
Author(s):  
E. Puil ◽  
R. M. Miura ◽  
I. Spigelman
Keyword(s):  
Membrane Potential ◽  
Dose Range ◽  
Membrane Potentials ◽  
Time Dependent ◽  
Membrane Properties ◽  
Neuronal Membrane ◽  
K Channels ◽  
Membrane Breakdown ◽  
Trigeminal Root ◽  
Ganglion Neurons

1. The effects of 4-aminopyridine (4-AP) on the electrical properties of 30 trigeminal root ganglion (TRG) neurons were determined from the membrane voltage responses to step and sinusoidal current injections using intracellular microelectrode techniques in in vitro slice preparations (guinea pigs). 2. Comparisons of results from 4-AP applications (0.05-5 mM) with those from tetraethylammonium (TEA) applications (0.1-10 mM) revealed very different actions of these agents. Both agents produced an increase in input resistance and a decrease in threshold for spike generation. Applications of 4-AP increased subthreshold oscillations of the membrane potential and enhanced the repetitive spike firing evoked by intracellular injections of current pulses. However, TEA applications blocked the potential oscillations and did not exaggerate repetitive spike discharges. Spontaneous spike activity or bursts were observed in four neurons that received 4-AP applications. 3. Membrane properties were determined in 20 of the 30 neurons by fitting impedance data in the frequency domain with a four-parameter membrane model by the use of computer-intensive techniques. In the majority of neurons, the time-invariant and time-dependent membrane conductances decreased during 4-AP application. The time constant for the time-dependent conductance also decreased, suggesting that the closing of K+-channels was facilitated in the membrane. 4. Applications of 4-AP in a dose range of 50 microM-5 mM produced rapid (approximately tens of seconds) responses of the neurons, resulting in a dose-dependent increase of the impedance magnitude functions and in a leftward shift of the resonant "humps" to lower frequencies. This shift indicates that the TRG neuronal membrane is capable of producing large voltage responses to current inputs at low frequencies. Recovery from the effects of 4-AP was slow (usually greater than 30 min). 5. Applications of 4-AP at high doses (greater than or equal to 1 mM) and at various imposed membrane potentials in four neurons resulted in poorly reversible unspecific changes in certain membrane parameters (increased input capacitance and conductance) and an insensitivity of the input conductance to the imposed membrane potential. These effects could be interpreted as membrane breakdown. 6. The tendencies of TRG neurons to fire repetitively and in bursts of spikes during 4-AP application result from the increased oscillatory behavior of their membrane potentials and changes in membrane resonance induced by presumed blockade of K+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Measurement of spontaneous neuronal membrane activity by time lapse confocal microscopy

1995 ◽  
Vol 53 ◽  
pp. 972-973
Author(s):  
R H. Selinfreund ◽  
A. H. Cornell-Bell
Keyword(s):  
Membrane Potential ◽  
Confocal Microscopy ◽  
Patch Clamp ◽  
Electrical Activity ◽  
Time Lapse ◽  
Neuronal Firing ◽  
Neuronal Membrane ◽  
Pituitary Cells ◽  
Patch Clamp Recording ◽  
Spontaneous Electrical Activity

Cellular electrophysiological properties are normally monitored by standard patch clamp techniques . The combination of membrane potential dyes with time-lapse laser confocal microscopy provides a more direct, least destructive rapid method for monitoring changes in neuronal electrical activity. Using membrane potential dyes we found that spontaneous action potential firing can be detected using time-lapse confocal microscopy. Initially, patch clamp recording techniques were used to verify spontaneous electrical activity in GH4\C1 pituitary cells. It was found that serum depleted cells had reduced spontaneous electrical activity. Brief exposure to the serum derived growth factor, IGF-1, reconstituted electrical activity. We have examined the possibility of developing a rapid fluorescent assay to measure neuronal activity using membrane potential dyes. This neuronal regeneration assay has been adapted to run on a confocal microscope. Quantitative fluorescence is then used to measure a compounds ability to regenerate neuronal firing.The membrane potential dye di-8-ANEPPS was selected for these experiments. Di-8- ANEPPS is internalized slowly, has a high signal to noise ratio (40:1), has a linear fluorescent response to change in voltage.

scholarly journals On the Wireless Microwave Sensing of Bacterial Membrane Potential in Microfluidic-Actuated Platforms

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3420
Author(s):  
Marc Jofre ◽  
Lluís Jofre ◽  
Luis Jofre-Roca
Keyword(s):  
Membrane Potential ◽  
Living Cells ◽  
Membrane Potentials ◽  
Electromagnetic Properties ◽  
Bacterial Membrane ◽  
Microfluidic Platforms ◽  
Bacterial Membranes ◽  
Wireless Monitoring ◽  
Bacterial Dynamics ◽  
Engineered Systems

The investigation of the electromagnetic properties of biological particles in microfluidic platforms may enable microwave wireless monitoring and interaction with the functional activity of microorganisms. Of high relevance are the action and membrane potentials as they are some of the most important parameters of living cells. In particular, the complex mechanisms of a cell’s action potential are comparable to the dynamics of bacterial membranes, and consequently focusing on the latter provides a simplified framework for advancing the current techniques and knowledge of general bacterial dynamics. In this work, we provide a theoretical analysis and experimental results on the microwave detection of microorganisms within a microfluidic-based platform for sensing the membrane potential of bacteria. The results further advance the state of microwave bacteria sensing and microfluidic control and their implications for measuring and interacting with cells and their membrane potentials, which is of great importance for developing new biotechnologically engineered systems and solutions.

The Effects of Low Energy X-Rays on Membrane Potential, Membrane Resistance and Action Potential of Nitella flexilis

1972 ◽  
Vol 50 (3) ◽  
pp. 491 ◽  
Author(s):  
E. M. Röttinger ◽  
O. Hug ◽  
E. M. Rottinger
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Membrane Resistance ◽  
Low Energy ◽  
X Rays ◽  
Nitella Flexilis

Thermal Acclimation of a Central Neurone in Helix Aspersa: III. Ionic Substitution and Related Studies

1979 ◽  
Vol 78 (1) ◽  
pp. 201-211
Author(s):  
C. K. LANGLEY
Keyword(s):  
Chemical Composition ◽  
Electrical Properties ◽  
Membrane Resistance ◽  
Thermal Acclimation ◽  
Neuronal Membrane ◽  
Electrical Characteristics ◽  
Ionic Substitution ◽  
Warm Acclimation ◽  
Sodium And Potassium ◽  
Made In

(1) Thermal acclimation of the Fi neurone does not appear to result from changes in the chemical composition of the haemolymph. This is deduced from the lack of effect on the electrical characteristics of control neurones of either pooled haemolymph from acclimated individuals, or variations in the experimental salines made in accordance with haemolymph analyses. (2) Changes in [Ca]0 tended to act cooperatively with temperature shifts to induce alterations in the electrical properties of the neurone, notably to increase excitability and lower membrane resistance. (3) Warm acclimation was associated with increased resting conductance of the neuronal membrane to sodium and potassium, whereas chloride conductance appeared little affected.

Modulation of membrane potential by an acetylcholine-activated potassium current in trout atrial myocytes

2007 ◽  
Vol 292 (1) ◽  
pp. R388-R395 ◽  
Author(s):  
Cristina E. Molina ◽  
Hans Gesser ◽  
Anna Llach ◽  
Lluis Tort ◽  
Leif Hove-Madsen
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Ventricular Myocytes ◽  
Reversal Potential ◽  
Membrane Potentials ◽  
Resting Membrane Potential ◽  
Atrial Myocytes ◽  
Atrial Tissue ◽  
Isolated Cardiac Myocytes ◽  
Inwardly Rectifying

Application of the current-clamp technique in rainbow trout atrial myocytes has yielded resting membrane potentials that are incompatible with normal atrial function. To investigate this paradox, we recorded the whole membrane current ( Im) and compared membrane potentials recorded in isolated cardiac myocytes and multicellular preparations. Atrial tissue and ventricular myocytes had stable resting potentials of −87 ± 2 mV and −83.9 ± 0.4 mV, respectively. In contrast, 50 out of 59 atrial myocytes had unstable depolarized membrane potentials that were sensitive to the holding current. We hypothesized that this is at least partly due to a small slope conductance of Im around the resting membrane potential in atrial myocytes. In accordance with this hypothesis, the slope conductance of Im was about sevenfold smaller in atrial than in ventricular myocytes. Interestingly, ACh increased Im at −120 mV from 4.3 pA/pF to 27 pA/pF with an EC50 of 45 nM in atrial myocytes. Moreover, 3 nM ACh increased the slope conductance of Im fourfold, shifted its reversal potential from −78 ± 3 to −84 ± 3 mV, and stabilized the resting membrane potential at −92 ± 4 mV. ACh also shortened the action potential in both atrial myocytes and tissue, and this effect was antagonized by atropine. When applied alone, atropine prolonged the action potential in atrial tissue but had no effect on membrane potential, action potential, or Im in isolated atrial myocytes. This suggests that ACh-mediated activation of an inwardly rectifying K+ current can modulate the membrane potential in the trout atrial myocytes and stabilize the resting membrane potential.

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