Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed.

Frequency-dependent avoidance movement of glass catfish in response to sinusoidal electrical stimulation and associated spiking patterns of electroreceptors.

The glass catfish is a freshwater fish with electroreceptors on its body surface. In this study, we investigated its behavioral response to sinusoidal electrical stimulation with a dipole wider than its body length and the spiking patterns of its electroreceptors. We observed that sinusoidal electric stimulation with a large dipole distance elicited in the glass catfish an avoidance movement whose frequency range is frequency-dependent. The movements were prominent in the frequency range between 10-20 Hz. When the stimulation strength increased, the movements were also found in the low-frequency range. In electrophysiological experiments, periodic interspike intervals of the electroreceptors were modulated by sinusoidal electrical stimuli. The stimulation introduced irregularity in the spiking patterns. The local variability of the spike modulations was significantly higher in the frequency range of 4-40 Hz and was particularly sensitive at 20 Hz. The avoidance movements and an increase in the local variability in the spike patterns were found around 20 Hz. Our results indicate that the glass catfish avoids sinusoidal electrical stimulation in a frequency-dependent manner, and this is associated with local modulations in the spiking patterns of the electroreceptors.

Taste Receptor Cells Generate Oscillating Receptor Potentials by Activating G Protein-Coupled Taste Receptors.

The receptor potentials of taste receptor cells remain unclear. Here, we demonstrate that taste receptor cells generate oscillating depolarization (n = 7) with action potentials in response to sweet, bitter, umami, and salty taste substances. At a lower concentration of taste substances, taste receptor cells exhibited oscillations in membrane potentials with a low frequency and small magnitude of depolarization. Although the respective waves contained no or 1-2 action potentials, the taste receptor cells generated action potentials continuously in the presence of taste stimuli. Both the frequency and magnitude of oscillations increased when the concentration was increased, to 0.67-1.43 Hz (n = 3) and Δ39-53 mV (n = 3) in magnitude from -64.7 ± 4.2 to -18.7 ± 5.9 mV, which may activate the ATP-permeable ion channels. In contrast, a sour tastant (10-mM HCl) induced membrane depolarization (Δ19.4 ± 9.5 mV, n = 4) with action potentials in type III taste receptor cells. Interestingly, NaCl (1 M) taste stimuli induced oscillation (n = 2) or depolarization (Δ10.5 ± 5.7 mV at the tonic component, n = 9). Our results indicate that the frequency and magnitude of oscillations increased with increasing taste substance concentrations. These parameters may contribute to the expression of taste "thickness."

Network model of chemical-sensing system inspired by mouse taste buds.

Taste buds endure extreme changes in temperature, pH, osmolarity, so on. Even though taste bud cells are replaced in a short span, they contribute to consistent taste reception. Each taste bud consists of about 50 cells whose networks are assumed to process taste information, at least preliminarily. In this article, we describe a neural network model inspired by the taste bud cells of mice. It consists of two layers. In the first layer, the chemical stimulus is transduced into an irregular spike train. The synchronization of the output impulses is induced by the irregular spike train at the second layer. These results show that the intensity of the chemical stimulus is encoded as the degree of the synchronization of output impulses. The present algorithms for signal processing result in a robust chemical-sensing system.

Random pulse induced synchronization and resonance in uncoupled non-identical neuron models.

Random pulses contribute to stochastic resonance in neuron models, whereas common random pulses cause stochastic-synchronized excitation in uncoupled neuron models. We studied concurrent phenomena contributing to phase synchronization and stochastic resonance following induction by a weak common random pulse in uncoupled non-identical Hodgkin-Huxley type neuron models. The common random pulse was selected from a gamma distribution and the degree of synchronization depended on the corresponding shape parameter. Specifically, a low shape parameter of the weak random pulse induced well-synchronized spiking in uncoupled neuron models, whereas a high shape parameter of the weak random pulse or a weak periodic pulse caused low degrees of synchronization. These were improved by concurrent inputs of periodic and random pulses with high shape parameters. Finally, the output pulse was synchronized with the periodic pulse, and the common random pulse revealed periodic responses in the present neuron models.

Development of Frequency Based Taste Receptors Using Bioinspired Glucose Nanobiosensor.

A method to fabricate a bioinspired nanobiosensor using electronic-based artificial taste receptors for glucose diagnosis is presented. Fabricated bioinspired glucose nanobiosensor designated based on an artificial taste bud including an amperometric glucose biosensor and taste bud-inspired circuits. In fact, the design of the taste bud-inspired circuits was inspired by the signal-processing mechanism of taste nerves which involves two layers. The first, known as a type II cell, detects the glucose by glucose oxidase and transduces the current signal obtained for the pulse pattern is conducted to the second layer, called type III cell, to induce synchronisation of the neural spiking activity. The oscillation results of fabricated bioinspired glucose nanobiosensor confirmed an increase in the frequency of the output pulse as a function of the glucose concentration. At high glucose concentrations, the bioinspired glucose nanobiosensor showed a pulse train of alternating short and long interpulse intervals. A computational analysis performed to validate the hypothesis, which was successfully reproduced the alternating behaviour of bioinspired glucose our nanobiosensor by increasing the output frequency and alternation of pulse intervals according to the reduction in the resistivity of the biosensor.

Stochastic resonance in the hippocampal CA3-CA1 model: a possible memory recall mechanism.

Stochastic resonance (SR) in a hippocampal network model was investigated. The hippocampal model consists of two layers, CA3 and CA1. Pyramidal cells in CA3 are connected to pyramidal cells in CA1 through Schaffer collateral synapses. The CA3 network causes spontaneous irregular activity (broadband spectrum peaking at around 3 Hz), while the CA1 network does not. The activity of CA3 causes membrane potential fluctuations in CA1 pyramidal cells. The CA1 network also receives a subthreshold signal (2.5 or 50 Hz) through the perforant path (PP). The subthreshold PP signals can fire CA1 pyramidal cells in cooperation with the membrane potential fluctuations that work as noise. The firing of the CA1 network shows typical features of SR. When the frequency of the PP signal is in the gamma range (50 Hz), SR that takes place in the present model shows distinctive features. 50 Hz firing of CA1 pyramidal cells is modulated by the membrane potential fluctuations, resulting in bursts. Such burst firing in the CA1 network, which resembles the firing patterns observed in the real hippocampal CA1, improves performance of subthreshold signal detection in CA1. Moreover, memory embedded at Schaffer collateral synapses can be recalled by means of SR. When Schaffer collateral synapses in subregions of CA1 are augmented three-fold as a memory pattern. pyramidal cells in the subregions respond to the subthreshold PP signal due to SR, while pyramidal cells in the rest of CA1 do not fire.

Dynamical properties of the two-process model for sleep-wake cycles in infantile autism.

The two-process model is a scheme for the timing of sleep that consists of homeostatic (Process S) and circadian (Process C) variables. The two-process model exhibits abnormal sleep patterns such as internal desynchronization or sleep fragmentation. Early infants with autism often experience sleep difficulties. Large day-by-day changes are found in the sleep onset and waking times in autistic children. Frequent night waking is a prominent property of their sleep. Further, the sleep duration of autistic children is often fragmented. These sleep patterns in infants with autism are not fully understood yet. In the present study, the sleep patterns in autistic children were reproduced by a modified two-process model using nonlinear analysis. A nap term was introduced into the original two-process model to reproduce the sleep patterns in early infants. The nap term and the time course of Process S are mentioned in the present study. Those parameters led to bifurcation of the sleep-wake cycle in the modified two-process model. In a certain range of these parameter sets, a small external noise was amplified, and an irregular sleep-wake cycle appeared. The short duration of sleep led to another irregular sleep onset or waking. Consequently, an irregular sleep-wake cycle appeared in early infantile autism.

Theta phase coding in a network model of the entorhinal cortex layer II with entorhinal-hippocampal loop connections.

We investigated successive firing of the stellate cells within a theta cycle, which replicates the phase coding of place information, using a network model of the entorhinal cortex layer II with loop connections. Layer II of the entorhinal cortex (ECII) sends signals to the hippocampus, and the hippocampus sends signals back to layer V of the entorhinal cortex (ECV). In addition to this major pathway, projection from ECV to ECII also exists. It is, therefore, inferred that reverberation activity readily appears if projections from ECV to ECII are potentiated. The frequency of the reverberation would be in a gamma range because it takes signals 20-30 ms to go around the entorhinal-hippocampal loop circuits. On the other hand, it has been suggested that ECII is a theta rhythm generator. If the reverberation activity appears in the entorhinal-hippocampal loop circuits, gamma oscillation would be superimposed on a theta rhythm in ECII like a gamma-theta oscillation. This is a reminiscence of the theta phase coding of place information. In this paper, first, a network model of ECII will be developed in order to reproduce a theta rhythm. Secondly, we will show that loop connections from one stellate cell to the other one are selectively potentiated by afferent signals to ECII. Frequencies of those afferent signals are different, and transmission delay of the loop connections is 20 ms. As a result, stellate cells fire successively within one cycle of the theta rhythm. This resembles gamma-theta oscillation underlying the phase coding. Our model also replicates the phase precession of stellate cell firing within a cycle of subthreshold oscillation (theta rhythm).

Complexity of spatiotemporal activity of a neural network model which depends on the degree of synchronization.

Spatiotemporal activity of a hippocampal CA3 model and its dynamic features were investigated. The CA3 model consists of 256 pyramidal cells and 25 inhibitory interneurons. Each pyramidal cell is a single-compartment model which was reduced from the 19-compartment cable model of the CA3 pyramidal cell developed by [Traub et al. (1991)]. Each interneuron is a model which causes tonic responses to constant depolarizing currents. The hippocampal model spontaneously causes four kinds of rhythms, A-D, which depend on the degree of synchronization of neuronal activity. The rhythm A (about 2Hz) which occurs in a range of strong mutual excitation is spatially coherent, though epileptiform bursts of pyramidal cells propagate from one end of the network to the other in a short period of time. The rhythm B (about 3Hz) occurs in an intermediate range of the strength of mutual excitation; synchronization of bursts is incomplete and the spatiotemporal pattern is complex. When the mutual excitation is relatively weak, the rhythm C (about 6Hz) occurs. Burst propagation is not uniform in direction, and the spatiotemporal activity is irregular. The rhythm D (10-35Hz) occurs in a range of weak mutual excitation when the recurrent inhibition is relatively strong. In this parameter region, pyramidal cells do not cause bursting discharges but irregular beating discharges. The hippocampal model causes phase-lockings and irregular responses to periodic synaptic stimulation depending on its own rhythmic activity and stimulus parameters. Bursting discharges of pyramidal cells are well synchronized in phase-locked responses. Several irregular responses of the rhythms A and B are evidently chaotic; each one-dimensional strobomap of chaotic responses is a non-invertible function with an unstable fixed point. Attractors reconstructed from chaotic responses demonstrate the stretching and folding mechanism.

Spontaneous initiation and termination of complex rhythms in cardiac cell culture.

INTRODUCTION: Complex cardiac arrhythmias often start and stop spontaneously. These poorly understood behaviors frequently are associated with pathologic modification of the structural heterogeneity and functional connectivity of the myocardium. To evaluate underlying mechanisms, we modify heterogeneity by varying the confluence of embryonic chick monolayer cultures that display complex bursting behaviors. A simple mathematical model was developed that reproduces the experimental behaviors and reveals possible generic mechanisms for bursting dynamics in heterogeneous excitable systems. METHODS AND RESULTS: Wave propagation was mapped in embryonic chick myocytes monolayers using calcium-sensitive dyes. Monolayer confluence was varied by plating cultures with different cell densities and by varying times in culture. At high plating densities, waves propagate without breaks, whereas monolayers plated at low densities display spirals with frequent breaks and irregular activation fronts. Monolayers at intermediate densities display bursting rhythms in which there is paroxysmal starting and stopping of spiral waves of activity. Similar spatiotemporal patterns of activity were also observed as a function of the time in culture; irregular activity dominates the first 30 hours, followed by repetitive bursting dynamics until 54 hours, after which periodic target patterns or stable spirals prevail. In some quiescent cultures derived from older embryos, it was possible to trigger pacemaker activity following a single activation. We are able to reproduce all of these behaviors by introducing spatial heterogeneity and varying neighborhood size, equivalent to cell connectivity, in a spontaneous cellular automaton model containing a rate-dependent fatigue term. CONCLUSION: We observe transitions from irregular propagating waves, to spiral waves that spontaneously start and stop, to target waves originating from localized pacemakers in cell culture and a simple theoretical model of heterogeneous excitable media. The results show how physiologic properties of spontaneous activity, heterogeneity, and fatigue can give rise to a wide range of different complex dynamic behaviors similar to clinically observed cardiac arrhythmias.