Functional subgroups of rat and human sensory neurons: a systematic review of electrophysiological properties

Sensory neurons are responsible for the generation and transmission of nociceptive signals from the periphery to the central nervous system. They encompass a broadly heterogeneous population of highly specialized neurons. The understanding of the molecular choreography of individual subpopulations is essential to understand physiological and pathological pain states. Recently, it became evident that species differences limit transferability of research findings between human and rodents in pain research. Thus, it is necessary to systematically compare and categorize the electrophysiological data gained from human and rodent dorsal root ganglia neurons (DRGs). In this systematic review, we condense the available electrophysiological data defining subidentities in human and rat DRGs. A systematic search on PUBMED yielded 30 studies on rat and 3 studies on human sensory neurons. Defined outcome parameters included current clamp, voltage clamp, cell morphology, pharmacological readouts, and immune reactivity parameters. We compare evidence gathered for outcome markers to define subgroups, offer electrophysiological parameters for the definition of neuronal subtypes, and give a framework for the transferability of electrophysiological findings between species. A semiquantitative analysis revealed that for rat DRGs, there is an overarching consensus between studies that C-fiber linked sensory neurons display a lower action potential threshold, higher input resistance, a larger action potential overshoot, and a longer afterhyperpolarization duration compared to other sensory neurons. They are also more likely to display an infliction point in the falling phase of the action potential. This systematic review points out the need of more electrophysiological studies on human sensory neurons.

Hyperexcitability of Sensory Neurons in Fragile X Mouse Model

Sensory hypersensitivity and somatosensory deficits represent the core symptoms of Fragile X syndrome (FXS). These alterations are believed to arise from changes in cortical sensory processing, while potential deficits in the function of peripheral sensory neurons residing in dorsal root ganglia remain unexplored. We found that peripheral sensory neurons exhibit pronounced hyperexcitability in Fmr1 KO mice, manifested by markedly increased action potential (AP) firing rate and decreased threshold. Unlike excitability changes found in many central neurons, no significant changes were observed in AP rising and falling time, peak potential, amplitude, or duration. Sensory neuron hyperexcitability was caused primarily by increased input resistance, without changes in cell capacitance or resting membrane potential. Analyses of the underlying mechanisms revealed reduced activity of HCN channels and reduced expression of HCN1 and HCN4 in Fmr1 KO compared to WT. A selective HCN channel blocker abolished differences in all measures of sensory neuron excitability between WT and Fmr1 KO neurons. These results reveal a hyperexcitable state of peripheral sensory neurons in Fmr1 KO mice caused by dysfunction of HCN channels. In addition to the intrinsic neuronal dysfunction, the accompanying paper examines deficits in sensory neuron association/communication with their enveloping satellite glial cells, suggesting contributions from both neuronal intrinsic and extrinsic mechanisms to sensory dysfunction in the FXS mouse model.

Ia EPSPs in rat spinal motoneurons are potentiated after a 5-week whole-body vibration

Whole-body vibration (WBV) is often applied as an alternative method for strength training or to prevent muscle force decrease. Previous studies indicated that WBV induced: 1) changes in the contractile parameters predominantly of fast motor units, 2) higher motoneuron excitability, and 3) higher motoneuron firing rates at lower stimulus intensities compared with the control. In this study, we evaluated the influence of WBV on Ia monosynaptic input from muscle spindles because the tonic vibration reflex is responsible for the enhancement of muscle activity observed after WBV. The aim was to answer the question of whether repeated activation of muscle spindles during WBV may result in altered synaptic excitation of motoneurons. WBV was performed on adult male Wistar rats, 5 days per week, for 5 weeks, and each daily session consisted of four 30-s runs of vibration at 50 Hz. Fast-type medial gastrocnemius motoneurons were investigated intracellularly in deeply anesthetized animals in the experimental (n=7, 34 motoneurons) and control (n=7, 32 motoneurons) groups. Monosynaptic Ia EPSPs were evoked by electrical stimulation of afferent fibers from the synergistic lateral gastrocnemius and soleus muscles. Data were analyzed using a mixed linear model. WBV induced an increase of the mean EPSP amplitude by 28% (P=0.025), correlated with the resting membrane potential and input resistance, and a shortening of the mean EPSP rise time by 11% (P=0.012). The potentiation of synaptic excitation of motoneurons indicates that WBV may support rehabilitation or training processes aimed at increasing muscle strength on the basis of increased motoneuronal drive.

When Are Depolarizing GABAergic Responses Excitatory?

The membrane responses upon activation of GABA(A) receptors critically depend on the intracellular Cl− concentration ([Cl−]i), which is maintained by a set of transmembrane transporters for Cl−. During neuronal development, but also under several pathophysiological conditions, the prevailing expression of the Cl− loader NKCC1 and the low expression of the Cl− extruder KCC2 causes elevated [Cl−]i, which result in depolarizing GABAergic membrane responses. However, depolarizing GABAergic responses are not necessarily excitatory, as GABA(A) receptors also reduces the input resistance of neurons and thereby shunt excitatory inputs. To summarize our knowledge on the effect of depolarizing GABA responses on neuronal excitability, this review discusses theoretical considerations and experimental studies illustrating the relation between GABA conductances, GABA reversal potential and neuronal excitability. In addition, evidences for the complex spatiotemporal interaction between depolarizing GABAergic and glutamatergic inputs are described. Moreover, mechanisms that influence [Cl−]i beyond the expression of Cl− transporters are presented. And finally, several in vitro and in vivo studies that directly investigated whether GABA mediates excitation or inhibition during early developmental stages are summarized. In summary, these theoretical considerations and experimental evidences suggest that GABA can act as inhibitory neurotransmitter even under conditions that maintain substantial depolarizing membrane responses.

Small Split-Ring Resonators as Efficient Antennas for Remote LoRa IOT Systems—A Path to Reduce Physical Interference

While wireless IOT modules can be made extremely compact, antennas typically protrude from the module, providing the potential to catch near moving/rotating equipment or transfer loads to the PCB through end forces, which can lead to failures. This work explores the use of split-ring resonator (SRR) designs to achieve a planar antenna with a maximum dimension less than a monopole working at the same frequency. The very narrow bandwidth of the SRR required detailed physical models to create printed circuit board (PCB)-based antenna designs that could be used at LoRa frequencies of 433 MHz and 915 MHz. Uncertainty analysis allowed for the impact of geometrical and physical tolerances on the resonant frequency to be evaluated. Nearfield and farfield measurements were performed allowing for the resonant frequency, directionality, and range of the antenna to be evaluated. An unbalanced SMA port was added to the SRR design to allow for the use of a network vector analyser to determine the input impedance of various designs. The optimum design achieved an input resistance of 44 Ω at a resonant frequency of 919 MHz, close to the target values (50 Ω at 915 MHz). Field measurements of the received signal strength from a planar antenna design indicated a gain of 5 dB over a conventional quarter-wave monopole antenna, in a footprint that was 40% smaller than the monopole.

Dravet Variant SCN1AA1783V Impairs Interneuron Firing Predominantly by Altered Channel Activation

Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional NaV1.1 haploinsufficiency in inhibitory interneurons. Recently, a new conditional mouse model expressing the recurrent human p.(Ala1783Val) missense variant has become available. In this study, we provided an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Based on these data, simulated interneuron (IN) firing properties in a conductance-based single-compartment model suggested surprisingly similar firing deficits for NaV1.1A1783V and full haploinsufficiency as caused by heterozygous truncation variants. Impaired NaV1.1A1783V channel activation was predicted to have a significantly larger impact on channel function than altered slow inactivation and is therefore proposed as the main mechanism underlying IN dysfunction. The computational model was validated in cortical organotypic slice cultures derived from conditional Scn1aA1783V mice. Pan-neuronal activation of the p.Ala1783V in vitro confirmed a predicted IN firing deficit and revealed an accompanying reduction of interneuronal input resistance while demonstrating normal excitability of pyramidal neurons. Altered input resistance was fed back into the model for further refinement. Taken together these data demonstrate that primary loss of function (LOF) gating properties accompanied by altered membrane characteristics may match effects of full haploinsufficiency on the neuronal level despite maintaining physiological peak current density, thereby causing DS.

A Novel Approach for the Design of Fast-Settling Amplifiers for Biosignal Detection

The most common method used to pick up biomedical signals is through metallic electrodes coupled to the input of high-gain, low-noise amplifiers. Unfortunately, electrodes, amongst other effects, introduce an undesired contact resistance and a contact potential. The contact potential needs to be rejected since it would otherwise cause the saturation of the input stage of the amplifiers, and this is almost always obtained by inserting a simple RC high-pass filter in the input signal path. The contact resistance needs to be estimated to ensure that it does not impair correct measurements. Methods exist for estimating the contact resistance by dynamically modifying the input network configuration, but because of the presence of the input RC filter, long transients are induced any time a switch occurs between different input configurations, so that the measurement time may become unacceptably long. In this paper, we propose a new topology for a DC removal network at the input of the differential signal amplifier that results in an AC filter whose time constant can be continuously changed by means of a control voltage. As such, we can speed up the recovery from transients by setting very short time constants (during the input resistance estimation process) while maintaining the ability to obtain very low cut-in frequencies by setting a much larger time constant during actual measurements. A prototype of the system was built and tested in order to demonstrate the advantage of the approach we propose in terms of reduced measurement time.

Generation of Electricity from Waste Heat

Thermo electric generation converts heat energy into electrical energy . Power generated from TEG depends on the temperature difference between hot and cold surface . To improve the efficiency of TEG, MPPT algorithm with boost converter is used . Maximum power is obtained in the system when the output resistance of the system matches with the input resistance of TEG. By modelling the power variations generated from TEG system in series and parallel were minimized . The proposed system consists of TEG with boost converter having P& O MPPT . This paper presents simulation model of TEG module using MATLAB and is successful in generating a stable output.