Inhibition of veratridine-induced delayed inactivation of the voltage-sensitive sodium channel by synthetic analogs of crambescin B

Crambescin B carboxylic acid, a synthetic analog of crambescin B, was recently found to inhibit the voltage-sensitive sodium channels (VSSC) in a cell-based assay using neuroblastoma Neuro 2A cells. In the present study, whole-cell patch-clamp recordings were conducted with three heterologously expressed VSSC subtypes, Na_v1.2, Na_v1.6 and Na_v1.7, in a human embryonic kidney cell line HEK293T to further characterize the inhibition of VSSC by crambescin B carboxylic acid. Contrary to the previous observation, crambescin B carboxylic acid did not inhibit peak current evoked by depolarization from the holding potential of ?100 mV to the test potential of ?10 mV in the absence or presence of veratridine (VTD). In the presence of VTD, however, crambescin B carboxylic acid diminished VTD-induced sustained and tail currents through the three VSSC subtypes in a dose-dependent manner, whereas TTX inhibited both the peak current and the VTD-induced sustained and tail currents through all subtypes of VSSC tested. We thus concluded that crambescin B carboxylic acid does not block VSSC in a similar manner to TTX but modulate the action of VTD, thereby causing an apparent block of VSSC in the cell-based assay.     

Flight-induced compass representation in the monarch butterfly heading network

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Modeling the spontaneous activity in suprachiasmatic nucleus neurons: Role of cation single channels

A population of interconnected neurons of the mammalian suprachiasmatic nuclei (SCN) controls circadian rhythms in physiological functions. In turn, a circadian rhythm of individual neurons is driven by intracellular processes, which via activation of specific membrane channels, produce circadian modulation of electrical firing rate. Yet the membrane target(s) of the cellular clock have remained enigmatic. Previously, subthreshold voltage-dependent cation (SVC) channels have been proposed as the membrane target of the cellular clock responsible for circadian modulation of the firing rate in SCN neurons. We tested this hypothesis with computational modeling based on experimental results from on-cell recording of SVC channel openings in acutely isolated SCN neurons and long-term continuous recording of activity from dispersed SCN neurons in a multielectrode array dish (MED). The model reproduced the circadian behavior if the number of SVC channels or their kinetics were modulated in accordance with protein concentration in a model of the intracellular clock (Scheper et al., 1999. J. Neurosci. 19, 40-47). Such modulation changed the average firing rate of the model neuron from zero (“subjective-night” silence) up to 18 Hz (“subjective-day” peak). Furthermore, the variability of interspike intervals (ISI) and the circadian pattern of firing rate (i.e. silence-to-activity ratio and shape of circadian peaks) are in reasonable agreement with experimental data obtained in dispersed SCN neurons in MED. These results suggest that the variability of ISI in intact SCN neurons is mostly due to stochastic single-channel openings, and that the circadian pattern of the firing rate is specified by threshold properties of dependence of the spontaneous firing rate on the number of single channels (R-N relationship). This plausible mathematical modeling supports the hypothesis that SVC channels could be a critical element in circadian modulation of firing rate in SCN neurons.     

Video‐recording complex health interactions in a diverse setting: Ethical dilemmas,reflections and recommendations

Video‐recording healthcare interactions provides important opportunities for research and service improvement. However, this method brings about tensions, especially when recording sensitive topics. Subsequent reflection may compel the researcher to engage in ethical and moral deliberations. This paper presents experiences from a South African genetic counselling study which made use of video‐recordings to understand communicative processes in routine practice. Video‐recording as a research method, as well as contextual and process considerations are discussed, such as researching one's own field, issues of trust and anonymity, the challenge of providing true informed consent and capturing details which may cause psychological harm. Several recommendations for research practice in diverse healthcare settings are made. This includes the value of reflective pieces, the importance of retrospective consent, disclosure of the limitations to anonymity, as well as the collective responsibility of those involved to produce ethical research. These recommendations have value for genetic counselling and other healthcare fields.     

Effects of the observation method (direct v. from video) and of the presence of an observer on behavioural results in veal calves

This study aimed at assessing the effect of the observation method (direct or from video) and the effect of the presence of an observer on the behavioural results in veal calves kept on a commercial farm. To evaluate the effect of the observation method, 20 pens (four to five calves per pen) were observed by an observer for 60 min (two observation sessions of 30 min) and video-recorded at the same time. To evaluate the effect of the presence of the observer in front of the pen, 24 pens were video-recorded on 4 consecutive days and an observer was present in front of each pen for 60 min (two observation sessions of 30 min) on the third day. Behaviour was recorded using instantaneous scan sampling. For the study of the observer's effect, the analysis was limited to the posture, abnormal oral behaviour and manipulation of substrates. The two observation methods gave similar results for the time spent standing, but different results for all other behaviours. The presence of an observer did not affect the behaviour of calves at day level; however, their behaviour was affected when the observer was actually present in front of the pens. A higher percentage of calves were standing and were manipulating substrate in the presence of the observer, but there was no effect on abnormal oral behaviour. In conclusion, direct observations are a more suitable observation method than observations from video recordings for detailed behaviours in veal calves. The presence of an observer has a short-term effect on certain behaviours of calves that will have to be taken into consideration when monitoring these behaviours.     

Connecting the dots in ethology: applying network theory to understand neural and animal collectives

A major goal shared by neuroscience and collective behavior is to understand how dynamic interactions between individual elements give rise to behaviors in populations of neurons and animals, respectively. This goal has recently become within reach, thanks to techniques providing access to the connectivity and activity of neuronal ensembles as well as to behaviors among animal collectives. The next challenge using these datasets is to unravel network mechanisms generating population behaviors. This is aided by network theory, a field that studies structure–function relationships in interconnected systems. Here we review studies that have taken a network view on modern datasets to provide unique insights into individual and collective animal behaviors. Specifically, we focus on how analyzing signal propagation, controllability, symmetry, and geometry of networks can tame the complexity of collective system dynamics. These studies illustrate the potential of network theory to accelerate our understanding of behavior across ethological scales.     

Antennal response of codling moth males, Cydia pomonella L. (Lepidoptera: Tortricidae), to the geometric isomers of codlemone and codlemone acetate

Single sensillum recordings from Cydia pomonella male antennae showed three different types of receptor neurons. The most abundant type was most sensitive to the main pheromone compound (E,E)-8,10-dodecadienol, while its response to the geometric isomers E,Z, Z,E and Z,Z was comparable to a tenfold lower dose of (E,E)-8,10-dodecadienol. This neuron type also responded to the four behaviorally antagonistic isomers of (Δ,Δ)-8,10-dodecadienyl acetate, among which it was most sensitive to the E,E isomer. Cross-adaptation studies showed that these compounds were all detected by the same receptor neuron type. Receptor neurons specifically tuned to (E,Z) or (Z,Z)-8,10-dodecadienol were not found, although these two compounds are behaviorally active. A second type of receptor neuron responded to all isomers of (Δ,Δ)-8,10-dodecadienyl acetate and was most sensitive to the E,E isomer. This neuron type did not respond to any of the isomers of (Δ,Δ)-8,10-dodecadienol. A third receptor neuron type was highly sensitive to the plant compound α-farnesene. The finding that the receptor neuron type tuned to the main pheromone compound responded even to strong behavioral antagonists aids the interpretation of ongoing behavioral studies for the development of the mating disruption technique in codling moth. Accepted: 3 March 2000