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Reingruber, J.

Publications and source records attributed to Reingruber, J..

4 recordsLinked to original sources

Electrodiffusion analysis of concentration and voltage changes in thin cylindrical domains using cross-diffusion modelling

A major challenge in neuroscience is to predict how currents in nanodomains affect voltage and ionic concentrations. Cable and Rall theory provide analytic current-voltage relations by neglecting concentration gradients, and the impact of concentration gradients is usually studied numerically with the Poisson-Nernst-Planck (PNP) model. A precise quantitative understanding of the combined dynamics remains limited because analytic current-voltage-concentration relations are missing. In this work we derive such relations using a novel approach based on cross-diffusion equations. For narrow cylindrical domains, we derive time-dependent and steady-state expressions that explicitly show how currents affect voltage and ionic concentrations. We find that the influx of only one ion can significantly change the concentrations of all the other ions even if no channels for these ions are present. After a current injection we compute a biphasic voltage transient where the small-time asymptotic corresponds to the steady-state solution of the cable equation. We show that the accuracy of cable theory prediction for the voltage depends on how the current is distributed among the various ions. Finally, we develop an iterative method to accurately compute steady-state profiles for voltage and concentrations using first-order results by subdividing a cylinder into small segments.

biophysics↗

Analysis of calcium dynamics for dim-light responses in rod and cone photoreceptors

Rod and cone photoreceptors in the retina of vertebrate eyes are fundamental sensory neurons underlying vision. They use a sophisticated signal transduction pathway consisting of a series of biochemical processes to convert the absorption of light into an electrical current response. Several of these processes are modulated by feedback that depends on the intracellular Ca2+ concentration. In this work we use a representative phototransduction model to study how changing the Ca2+ kinetics by fast buffering affects sensitivity and dynamics of the light response in mouse rod and cone photoreceptors. We derive analytic results for dim-light stimulations that provide quantitative and conceptual insight. We show that flash responses are monophasic with low buffering, and the change in the Ca2+ concentration occurs in proportion to the current. If the amount of fast buffering is increased, the Ca2+ kinetics becomes slowed down and delayed with respect to the current, and biphasic responses emerge (damped oscillations). This shows that a biphasic response is not necessarily a manifestation of slow buffering reactions. A phase space analysis shows that the emergence of biphasic responses depends on the ratio between the effective rate ca that controls the Ca2+ kinetics, and the dark turnover rate of cyclic GMP {beta}d. We further investigate how the light response is altered by modifying the extracellular Ca2+ concentration. In summary, we provide a comprehensive quantitative analysis that precisely links the dynamics of Ca2+ concentration to the observed current response.

biophysics↗

The Ca2+-activated Cl- current ensures robust and reliable signal amplification in vertebrate olfactory receptor neurons

Activation of most primary sensory neurons results in transduction currents that are carried by cations. One notable exception is the vertebrate olfactory receptor neuron (ORN), where the transduction current is carried largely by the anion Cl-. However, it remains unclear why ORNs use an anionic current for signal amplification. We have sought to provide clarification on this topic by studying the so far neglected dynamics of Na+, Ca2+, K+ and Cl- in the small space of olfactory cilia during an odorant response. Using computational modeling and simulations we compared the outcomes of signal amplification based on either Cl- or Na+ currents. We found that amplification produced by Na+ influx instead of a Cl- efflux is problematic due to several reasons: First, the Na+ current amplitude varies greatly depending on mucosal ion concentration changes. Second, a Na+ current leads to a large increase in the ciliary Na+ concentration during an odorant response. This increase inhibits and even reverses Ca2+ clearance by Na+/Ca2+/K+ exchange, which is essential for response termination. Finally, a Na+ current increases the ciliary osmotic pressure, which could cause swelling to damage the cilia. By contrast, a transduction pathway based on Cl- efflux circumvents these problems and renders the odorant response robust and reliable.

neuroscience↗

Asymmetric ephaptic inhibition between compartmentalized olfactory receptor neurons

In the Drosophila antenna, different subtypes of olfactory receptor neurons (ORNs) housed in the same sensory hair (sensillum) can inhibit each other non-synaptically. However, the mechanisms underlying this unusual form of lateral inhibition remain unclear. Here we use recordings from pairs of sensilla impaled by the same tungsten electrode to prove that direct electrical (\"ephaptic\") interactions mediate lateral inhibition between ORNs. Intriguingly, within individual sensilla, we find that ephaptic lateral inhibition is asymmetric such that one ORN exerts greater influence onto its neighbor. Serial block-face scanning electron microscopy of genetically identified ORNs and circuit modeling indicate that asymmetric lateral inhibition reflects a surprisingly simple mechanism: the physically larger ORN in a pair corresponds to the dominant neuron in ephaptic interactions. Thus, morphometric differences between compartmentalized ORNs account for highly specialized inhibitory interactions that govern information processing at the earliest stages of olfactory coding.

neuroscience↗