Mammalian Cold Receptor Research Articles

Obstacle induced spiral waves in a multilayered Huber-Braun (HB) neuron model.

Various dynamical properties of four-dimensional mammalian cold receptor model have been discussed widely in the literature considering noise and temperature as important parameters of discussion. Though various spiking and bursting behaviors of the neuron under various noise and temperature conditions studied for a single neuron, no much discussions have been done on the collective behavior. We investigate the collective behavior of these temperature dependent stochastic neurons and unlike the neuron models when forced by periodic external force there is no wave reentry or spiral waves in the network. Hence, we introduce obstacle in the network and depending on the orientation and size of the introduced obstacle, we could show their effects on the wave reentry in the network. Various significant discussions are produced in this paper to confirm that obstacles placed parallel to the wave entry affects the excitability of the tissues significantly compared to those obstacles place perpendicular. We could also show that those obstacles which are lesser in dimensions doesn't affect the excitabilities and hence doesn't contribute for wave reentry. We introduce a new technique to identify wave reentry and spiral waves using the period of individual nodes is proposed. This technique could help us identify even the lowest of excitability change which cannot be seen when using spatiotemporal snapshots.

Switch Elements with S-Shaped Current-Voltage Characteristic in Models of Neural Oscillators

In this paper, we present circuit solutions based on a switch element with the S-type I–V characteristic implemented using the classic FitzHugh–Nagumo and FitzHugh–Rinzel models. Using the proposed simplified electrical circuits allows the modeling of the integrate-and-fire neuron and burst oscillation modes with the emulation of the mammalian cold receptor patterns. The circuits were studied using the experimental I–V characteristic of an NbO2 switch with a stable section of negative differential resistance (NDR) and a VO2 switch with an unstable NDR, considering the temperature dependences of the threshold characteristics. The results are relevant for modern neuroelectronics and have practical significance for the introduction of the neurodynamic models in circuit design and the brain–machine interface. The proposed systems of differential equations with the piecewise linear approximation of the S-type I–V characteristic may be of scientific interest for further analytical and numerical research and development of neural networks with artificial intelligence.

Phase description of the Huber-Braun neuron model for mammalian cold receptors

The spiking activity of mammalian cold receptors is described by the Huber-Braun neuron model. Sweeping temperature as a control parameter across a biologically relevant range this model exhibits a complex bifurcation structure seen in the sequence of interspike intervals. The model’s distinctive feature is the interaction between a fast spike generating dynamics and a slow subthreshold oscillation. Viewing the spike generation as a cycle, the dynamics may also be modeled phenomenologically by two phases, one for the spike cycle and the second for the slow subthreshold oscillation. In fact, a phase model of temperature-dependent mammalian cold receptors was already proposed by Roper et al. (2000). Here we follow their approach and investigate to what extent this model is able to reproduce the bifurcation patterns of the Huber-Braun model. Special attention is paid to the tonic firing to bursting transition observed in the low temperature range.

Ion channel drug potency assay with an artificial bilayer chip

The potency of pharmaceutical compounds acting on ion channels can be determined through measurements of ion channel conductance as a function of compound concentration. We have developed an artificial lipid bilayer chip for simple, fast, and high-yield measurement of ion channel conductance with simultaneous solution perfusion. Here we show the application of this chip to the measurement of the mammalian cold and menthol receptor TRPM8. Ensemble measurements of TRPM8 as a function of concentration of menthol and 2-aminoethoxydiphenyl borate (2-APB) enabled efficient determination of menthol's EC(50) (111.8 μM ± 2.4 μM) and 2-APB's IC(50) (4.9 μM ± 0.2 μM) in agreement with published values. This validation, coupled with the compatibility of this platform with automation and parallelization, indicates significant potential for large-scale pharmaceutical ion channel screening.

Temperature-dependent stochastic dynamics of the Huber-Braun neuron model

The response of a four-dimensional mammalian cold receptor model to different implementations of noise is studied across a wide temperature range. It is observed that for noisy activation kinetics, the parameter range decomposes into two regions in which the system reacts qualitatively completely different to small perturbations through noise, and these regions are separated by a homoclinic bifurcation. Noise implemented as an additional current yields a substantially different system response at low temperature values, while the response at high temperatures is comparable to activation-kinetic noise. We elucidate how this phenomenon can be understood in terms of state space dynamics and gives quantitative results on the statistics of interspike interval distributions across the relevant parameter range.

On the role of subthreshold currents in the Huber–Braun cold receptor model

We study the role of the strength of subthreshold currents in a four-dimensional Hodgkin-Huxley-type model of mammalian cold receptors. Since a total diminution of subthreshold activity corresponds to a decomposition of the model into a slow, subthreshold, and a fast, spiking subsystem, we first elucidate their respective dynamics separately and draw conclusions about their role for the generation of different spiking patterns. These results motivate a numerical bifurcation analysis of the effect of varying the strength of subthreshold currents, which is done by varying a suitable control parameter. We work out the key mechanisms which can be attributed to subthreshold activity and furthermore elucidate the dynamical backbone of different activity patterns generated by this model.

Noisy activation kinetics induces bursting in the Huber-Braun neuron model

We study a physiologically realistic implementation of internal stochasticity in a four-dimensional Hodgkin-Huxley type model of mammalian cold receptors. We show that in a deterministically tonic firing regime, this stochasticity can drive the neuron into a state of complex bursting behaviour. An explanation of the mechanism behind this effect is given in terms of phase space dynamics.

Stochastic encoding in sensory neurons: impulse patterns of mammalian cold receptors

Intrinsic oscillations at the level of the membrane potential are a widespread feature of nerve cells. Several evidences exist that, in particular, sensory neurons combine their oscillatory membrane potentials with intrinsic, membrane and/or synaptic noise to obtain sensitive encoding properties. An interesting example are mammalian cold receptors where stimulus transduction results from modulation of intrinsic receptor oscillations with essential contribution of noise thereby generating a rich spectrum of impulse patterns. To further explore the dynamics of these receptors we here investigate an HH-type model for oscillations and spike initiation in cold receptors. By use of a biophysically plausible temperature scaling and with addition of noise, the model successfully mimicks the principle temperature-dependence of stationary impulse patterns of real cold receptors. Our results suggest that interactions between stochastic and deterministic dynamics are of functional importance for the encoding charcteristics of cold receptors.

A phase model of temperature-dependent mammalian cold receptors.

We present a tractable stochastic phase model of the temperature sensitivity of a mammalian cold receptor. Using simple linear dependencies of the amplitude, frequency, and bias on temperature, the model reproduces the experimentally observed transitions between bursting, beating, and stochastically phase-locked firing patterns. We analyze the model in the deterministic limit and predict, using a Strutt map, the number of spikes per burst for a given temperature. The inclusion of noise produces a variable number of spikes per burst and also extends the dynamic range of the neuron, both of which are analyzed in terms of the Strutt map. Our analysis can be readily applied to other receptors that display various bursting patterns following temperature changes.

Encoding with Bursting, Subthreshold Oscillations, and Noise in Mammalian Cold Receptors

Mammalian cold thermoreceptors encode steady-state temperatures into characteristic temporal patterns of action potentials. We propose a mechanism for the encoding process. It is based on Plant's ionic model of slow wave bursting, to which stochastic forcing is added. The model reproduces firing patterns from cat lingual cold receptors as the parameters most likely to underlie the thermosensitivity of these receptors varied over a 25 degrees C range. The sequence of firing patterns goes from regular bursting, to simple periodic, to stochastically phase-locked firing or "skipping." The skipping at higher temperatures is shown to necessitate an interaction between noise and a subthreshold endogenous oscillation in the receptor. The basic period of all patterns is robust to noise. Further, noise extends the range of encodable stimuli. An increase in firing irregularity with temperature also results from the loss of stability accompanying the approach by the slow dynamics of a reverse Hopf bifurcation. The results are not dependent on the precise details of the Plant model, but are generic features of models where an autonomous slow wave arises through a Hopf bifurcation. The model also addresses the variability of the firing patterns across fibers. An alternate model of slow-wave bursting (Chay and Fan 1993) in which skipping can occur without noise is also analyzed here in the context of cold thermoreception. Our study quantifies the possible origins and relative contribution of deterministic and stochastic dynamics to the coding scheme. Implications of our findings for sensory coding are discussed.

Discharge pattern analysis suggests existence of a low-threshold calcium channel in cold receptors

The regular periodic activity patterns of mammalian cold receptors have been quantitatively studied. Analysis of the timing of either single impulses or impulse groups demonstrated that the periodic receptor process is maintained independently of impulse generation and continues to operate under conditions when afferent impulses are not initiated. These results imply that the underlying conductances must be operational at threshold potentials related to impulse generation. In addition to temperature, the periodic process is considerably sensitive to calcium, which affects mainly the probability of impulse generation during each cycle. Reduction of external calcium and application of calcium entry blockers with relative selectivity for low-threshold calcium channels are similarly effective in modulating cold receptor activity. The data imply the existence of a low-threshold calcium conductance at the sensory terminal.

Analysis of facial cold receptor activity in the rat

Afferent activity of single facial cold receptors was extracellularly recorded from infraorbital nerve fibers in the rat, and the response properties of 28 receptors to thermal stimulation were quantitatively studied. Generally, on repeated stimulation, the afferent activity was highly reproducible and was not dependent on previous adapting temperatures. At constant temperatures, a periodic pattern was apparent in the discharges of 24 receptors; in the remaining 4 receptors periodic elements could not reliably be detected. The temperature dependence of the cyclic pattern corresponded to that observed in other mammalian cold receptor populations: we observed regular impulse groups (bursts) at lower and beating activity at higher adapting temperatures. Rapid changes of temperature induced transient alterations of activity. The dynamic response to cooling was biphasic, indicating a complex sequence of receptor events. A transient acceleration of impulse frequency was followed by a dynamic burst discharge which was characterized by longer pauses and a greater number of impulses per burst compared with the steady-state activity at the same temperature. This indicates a deceleration of the periodic receptor events during the adaptation process following dynamic responses, which is accompanied by a concomitant shift of these processes to a more pronounced suprathreshold condition. In an additional series of experiments, parameters of the periodic activity in the rat were compared with corresponding data of facial and lingual cold receptors in the cat. Whereas the number of impulses per cycle was similar in the 3 receptor populations, the frequency of the periodic pattern proved to be considerably higher in the rat than in the cat.

Analysis of avian cold receptor function

The response characteristics of facial specific cold receptors of the pigeon were studied quantitatively by recording single unit activity from the trigeminal ganglion at various stimulus conditions and subsequent analysis of the discharge pattern. Responses to maintained temperatures as well as to cooling steps were qualitatively identical to those seen in the corresponding mammalian cold receptor populations, but avian cold receptors were generally less sensitive, particularly to dynamic stimuli. The major differences between avian and mammalian cold receptors were that avian cold units only occasionally discharged in periodic groups of impulses at constant temperatures and that there was no indication of cyclic receptor events being involved in the dynamic response to cooling, as it is the case in all mammalian cold sensors. Additionally, the temporal pattern of the grouped discharges was less regular in avian cold units. Application of calcium, EGTA and menthol revealed a comparatively low dependence of cold receptor function on external calcium. The results provide evidence that calcium-controlled processes and periodic receptor events contribute only insignificantly to the signal transduction of avian cold receptors. This indicates a different functional organization of the transducer processes of avian and mammalian cold receptors.

Mammalian cold receptor afferents: role of an electrogenic sodium pump in sensory transduction

Abstract : The responses of specific cold-sensitive afferents and cold-sensitive mechano-receptors were recorded from rat pudendal nerve. A local infiltration of ouabain into the region of the afferent terminals caused a dramatic increase in discharge at warm temperatures without significant effect on discharge in the cold. These results suggest that an electrogenic sodium pump is the generator potential mechanism imparting cold sensitivity. (Author)