This article develops a fundamental insight into the behavior of neuronal membranes, focusing on their responses to stimuli measured with power spectra in the frequency domain. It explores the use of linear and nonlinear (quadratic sinusoidal analysis) approaches to characterize neuronal function. It further delves into the random theory of internal noise of biological neurons and the use of stochastic Markov models to investigate these fluctuations. The text also discusses the origin of conductance noise and compares different power spectra for interpreting this noise. Importantly, it introduces a novel sequential chemical state model, named p2, which is more general than the Hodgkin-Huxley formulation, so that the probability for an ion channel to be open does not imply exponentiation. In particular, it is demonstrated that the p2 (without exponentiation) and n4 (with exponentiation) models can produce similar neuronal responses. A striking relationship is also shown between fluctuation and quadratic power spectra, suggesting that voltage-dependent random mechanisms can have a significant impact on deterministic nonlinear responses, themselves known to have a crucial role in the generation of action potentials in biological neural networks.

Calibration of the vestibulo-ocular reflex (VOR) depends on the presence of visual feedback. However, the cellular mechanisms associated with VOR modifications at the level of the brainstem remain largely unknown. A new protocol was designed to expose freely behaving mice to a visuo-vestibular mismatch during a 2-week period. This protocol induced a 50% reduction of the VOR. In vivo pharmacological experiments demonstrated that the VOR reduction depends on changes located outside the flocculus/paraflocculus complex. The cellular mechanisms associated with the VOR reduction were then studied in vitro on brainstem slices through a combination of vestibular afferent stimulation and patch-clamp recordings of central vestibular neurons. The evoked synaptic activity demonstrated that the efficacy of the synapses between vestibular afferents and central vestibular neurons was decreased. In addition, a long-term depression protocol failed to further decrease the synapse efficacy, suggesting that the VOR reduction might have occurred through depression-like mechanisms. Analysis of the intrinsic membrane properties of central vestibular neurons revealed that the synaptic changes were supplemented by a decrease in the spontaneous discharge and excitability of a subpopulation of neurons. Our results provide evidence that a long-lasting visuo-vestibular mismatch leads to changes in synaptic transmission and intrinsic properties of central vestibular neurons in the direct VOR pathway. Overall, these results open new avenues for future studies on visual and vestibular interactions conducted in vivo and in vitro.

Recently H-3(+) was detected at Saturn's low- and mid-latitudes for the first time (O'Donoghue et al. [2013]. Nature 496(7444), 193-195), revealing significant latitudinal structure in H-3(+) emissions, with local extrema in one hemisphere mirrored at magnetically conjugate latitudes in the opposite hemisphere. The observed minima and maxima were shown to map to regions of increased or decreased density in Saturn's rings, implying a direct ring-atmosphere connection. Here, using the Saturn Thermosphere Ionosphere Model (STIM), we investigate the "ring rain" explanation of the O'Donoghue et al. (O'Donoghue et al. [2013]. Nature 496(7444), 193-195) observations, wherein charged water group particles from the rings are guided by magnetic field lines as they "rain" down upon the atmosphere, altering local ionospheric chemistry. Based on model reproductions of observed H variations, we derive maximum water influxes of (1.6-16) x 10(5) H2O molecules cm(-2) s(-1) across ring rain latitudes (similar to 23-49 degrees in the south, and similar to 32-54 degrees in the north), with localized regions of enhanced influx near -48 degrees, -38 degrees, 42 degrees, and 53 degrees latitude. We estimate the globally averaged maximum ring-derived water influx to be (1.6-12) x 10(5) cm(-2) s(-1), which represents a maximum total global influx of water from Saturn's rings to its atmosphere of (1.0-6.8) x 10(26) s(-1). The wide range of global water influx estimates stems primarily from uncertainties regarding H-3(+) temperatures (and consequently column densities). Future ring rain observations may therefore be able to reduce these uncertainties by determining H-3(+) temperatures self consistently. (C) 2014 Elsevier Inc. All rights reserved.

The neurons in layer II of the medial entorhinal cortex are part of the grid cell network involved in the representation of space. Many of these neurons are likely to be stellate cells with specific oscillatory and firing properties important for their function. A fundamental understanding of the nonlinear basis of these oscillatory properties is critical for the development of theories of grid cell firing. In order to evaluate the behavior of stellate neurons, measurements of their quadratic responses were used to estimate a second order Volterra kernel. This paper uses an operator theory, termed quadratic sinusoidal analysis (QSA), which quantitatively determines that the quadratic response accounts for a major part of the nonlinearity observed at membrane potential levels characteristic of normal synaptic events. Practically, neurons were probed with multi-sinusoidal stimulations to determine a Hermitian operator that captures the quadratic function in the frequency domain. We have shown that the frequency content of the stimulation plays an important role in the characteristics of the nonlinear response, which can distort the linear response as well. Stimulations with enhanced low frequency amplitudes evoked a different nonlinear response than broadband profiles. The nonlinear analysis was also applied to spike frequencies and it was shown that the nonlinear response of subthreshold membrane potential at resonance frequencies near the threshold is similar to the nonlinear response of spike trains.

Expertise in processing radio occultation observations, which provide vertical profiles of atmospheric and ionospheric properties from measurements of the frequency of radio signals, is not widespread amongst the planetary science community. In order to increase the population of radio occultation processing experts, which will have positive consequences for this field, here we provide detailed instructions for one critical aspect of radio occultation data processing: how to obtain a series of bending angles as a function of the ray impact parameter from a time series of frequency residuals. As developed, this tool is valid only for one-way, single frequency occultations at spherically symmetric objects, and is thus not immediately applicable to either two-way occultations, such as those of Mars Express, or occultations at oblate objects, such as Jupiter or Saturn. This tool is demonstrated successfully on frequency residuals from a Mars Global Surveyor occultation at Mars, and the resultant set of bending angles and impact parameters are used to obtain vertical profiles of ionospheric electron density, neutral atmospheric number density, mass density, pressure, and temperature via the usual Abel transform. The root-mean-square difference between electron densities in the ionospheric profile derived herein and archived electron densities is 7×108m−3. At the lowest altitudes, temperatures in the neutral atmospheric profile derived herein differ from archived neutral temperatures by less than 0.1K. Software programs that implement these procedures accompany this paper and may be used to extract scientifically useful data products from lower-level data sets.

The nonlinear properties of the dendrites of the prepositus hypoglossi nucleus (PHN) neurons are essential for the operation of the vestibular neural integrator that converts a head velocity signal to one that controls eye position. A novel system of frequency probing , namely quadratic sinusoidal analysis (QSA), was used to decode the intrinsic nonlinear behavior of these neurons under voltage clamp conditions. Voltage clamp currents were measured at harmonic and interactive frequencies using specific nonoverlapping stimulation frequencies. Eigenanalysis of the QSA matrix reduces it to a remarkably compact processing unit, composed of just one or two dominant components (eigenvalues). The QSA matrix of rat PHN neurons provides signatures of the voltage dependent conductances for their particular dendritic and somatic distributions. An important part of the nonlinear response is due to the persistent sodium conductance (gNaP), which is likely to be essential for sustained effects needed for a neural integrator. It was found that responses in the range of 10 mV peak to peak could be well described by quadratic nonlinearities suggesting that effects of higher degree nonlinearities would add only marginal improvement. Therefore, the quadratic response is likely to sufficiently capture most of the nonlinear behavior of neuronal systems except for extremely large synaptic inputs. Thus, neurons have two distinct linear and quadratic functions, which shows that piecewise linear + quadratic analysis is much more complete than just piecewise linear analysis; in addition quadratic analysis can be done at a single holding potential. Furthermore, the nonlinear neuronal responses contain more frequencies over a wider frequency band than the input signal. As a consequence, they convert limited amplitude and bandwidth input signals to wider bandwidth and more complex output responses. Finally, simulations at subthreshold membrane potentials with realistic PHN neuron models suggest that the quadratic functions are fundamentally dominated by active dendritic structures and persistent sodium conductances.

We present comprehensive calculations of the steady state response of Saturn's coupled thermosphere-ionosphere to forcing by solar radiation, magnetospheric energetic electron precipitation and high latitude electric fields caused by sub-corotation of magnetospheric plasma. Significant additions to the physical processes calculated in our Saturn Thermosphere Ionosphere General Circulation Model (STIM-GCM) include the comprehensive and self-consistent treatment of neutral-ion dynamical coupling and the use of self-consistently calculated rates of plasma production from incident energetic electrons. Our simulations successfully reproduce the observed high latitude temperatures as well as the latitudinal variations of ionospheric peak electron densities that have been observed by the Cassini Radio Science Subsystem experiment (RSS). We find magnetospheric energy deposition to strongly control the flow of mass and energy in the high and mid-latitude thermosphere and thermospheric dynamics to play a crucial role in driving this flow, highlighting the importance of including dynamics in any high latitude energy balance studies on Saturn and other Gas Giants. By relating observed H-3(+) column emissions and temperatures to the same quantities inferred from simulated atmosphere profiles we identify a potential method of better constraining the still unknown abundance of vibrationally excited H-2 which strongly affects the H-3(+) densities. Our calculations also suggest that local time variability in H-3(+) column emission flux may be largely driven by local time changes of H-3(+) densities rather than temperatures. By exploring the parameter space of possible high latitude electric field strengths and incident energetic electron fluxes, we determine the response of thermospheric polar temperatures to a range of these magnetospheric forcing parameters, illustrating that 10 key electron fluxes of 0.1-1.2 mW m(-2) in combination with electric field strengths of 80-100 mV m(-1) produce H-3(+) emissions consistent with observations. Our calculations highlight the importance of considering thermospheric temperatures as one of the constraints when examining the state of Saturn's magnetosphere and its coupling to the upper atmosphere. (C) 2012 Elsevier Inc. All rights reserved.

Nonlinear biophysical properties of individual neurons are known to play a major role in the nervous system, especially those active at subthreshold membrane potentials that integrate synaptic inputs during action potential initiation. Previous electrophysiological studies have made use of a piecewise linear characterization of voltage clamped neurons, which consists of a sequence of linear admittances computed at different voltage levels. In this paper, a fundamentally new theory is developed in two stages. First, analytical equations are derived for a multi-sinusoidal voltage clamp of a Hodgkin-Huxley type model to reveal the quadratic response at the ionic channel level. Second, the resulting behavior is generalized to a novel Hermitian neural operator, which uses an algebraic formulation capturing the entire quadratic behavior of a voltage clamped neuron. In addition, this operator can also be used for a nonlinear identification analysis directly applicable to experimental measurements. In this case, a Hermitian matrix of interactions is built with paired frequency probing measurements performed at specific harmonic and interactive output frequencies. More importantly, eigenanalysis of the neural operator provides a concise signature of the voltage dependent conductances determined by their particular distribution on the dendritic and somatic membrane regions of neurons. Finally, the theory is concretely illustrated by an analysis of an experimentally measured vestibular neuron, providing a remarkably compact description of the quadratic responses involved in the nonlinear processing underlying the control of eye position during head rotation, namely the neural integrator.

Head motion-related sensory signals are transformed by second-order vestibular neurons (2°VNs) into appropriate commands for retinal image stabilization during body motion.In frogs, these 2°VNs form two distinct subpopulations that have either tonic or highly phasic intrinsic properties, essentially compatible with low-pass and bandpass filter characteristics, respectively.In the present study, physiological data on cellular properties of 2°VNs of the grass frog (Rana temporaria) have been used to construct conductance-based spiking cellular models that were fine-tuned by fitting to recorded spike-frequency data.The results of this approach suggest that low-threshold, voltage-dependent potassium channels in phasic and spike-dependent potassium channels in tonic 2°VNs are important contributors to the differential, yet complementary response characteristics of the two vestibular subtypes.Extension of the cellular model with conductance-based synapses allowed simulation of afferent excitation and evaluation of the emerging properties of local feedforward inhibitory circuits.This approach revealed the relative contributions of intrinsic and synaptic factors on afferent signal processing in phasic 2°VNs.Additional extension of the single-cell model to a population model allowed testing under more natural conditions including asynchronous afferent labyrinthine input and synaptic noise.This latter approach indicated that the feedforward inhibition from the local inhibitory network acts as a high-pass filter, which reinforces the impact of the intrinsic membrane properties of phasic 2°VNs on peak response amplitude and timing.Thus, the combination of cellular and network properties enables phasic 2°VNs to work as a noise-resistant detector, suitable for central processing of short-duration vestibular signals.

Intrinsic cellular properties of neurons in culture or slices are usually studied by the whole cell clamp method using low-resistant patch pipettes. These electrodes allow detailed analyses with standard electrophysiological methods such as current- or voltage-clamp. However, in these preparations large parts of the network and dendritic structures may be removed, thus preventing an adequate study of synaptic signal processing. Therefore, intact in vivo preparations or isolated in vitro whole brains have been used in which intracellular recordings are usually made with sharp, high-resistant electrodes to optimize the impalement of neurons. The general non-linear resistance properties of these electrodes, however, severely limit accurate quantitative studies of membrane dynamics especially needed for precise modelling. Therefore, we have developed a frequency-domain analysis of membrane properties that uses a Piece-wise Non-linear Electrode Compensation (PNEC) method. The technique was tested in second-order vestibular neurons and abducens motoneurons of isolated frog whole brain preparations using sharp potassium chloride- or potassium acetate-filled electrodes. All recordings were performed without online electrode compensation. The properties of each electrode were determined separately after the neuronal recordings and were used in the frequency-domain analysis of the combined measurement of electrode and cell. This allowed detailed analysis of membrane properties in the frequency-domain with high-resistant electrodes and provided quantitative data that can be further used to model channel kinetics. Thus, sharp electrodes can be used for the characterization of intrinsic properties and synaptic inputs of neurons in intact brains.

Neural integrators and working memory rely on persistent activity, a widespread neural phenomenon potentially involving persistent sodium conductances. Using a unique combination of voltage-clamp, dynamic-clamp, and frequency-domain techniques, we have investigated the role of voltage-dependent conductances on the dendritic electrotonic structure of neurons of the prepositus hypoglossi nucleus (PHN), which is known to be involved in oculomotor integration. The PHN contains two main neuronal populations: type B neurons with a double afterhyperpolarization and type D neurons, which not only are oscillatory but also have a greater electrotonic length than that of type B neurons. The persistent sodium conductance is present in all PHN neurons, although its effect on the dynamic electrotonic structure is shown to significantly differ in the two major cell types present in the nucleus. The electrotonic differences are such that the persistent sodium conductance can be almost perfectly manipulated in a type B neuron using an on-line dynamic clamp to add or subtract virtual sodium ion channels. The dynamic-clamp results are confirmed by data-fitted models, which suggest that the persistent sodium conductance has two different roles depending on its somatic versus dendritic location: perisomatic conductances could play a major role in maintaining action potential discharge and dendritic conductances would be more involved in other computational properties, such as those involving remote synaptic processing or bistable events.

The sensory–motor transformation of the large dynamic spectrum of head-motion-related signals occurs in separate vestibulo-ocular pathways. Synaptic responses of tonic and phasic second-order vestibular neurons were recorded in isolated frog brains after stimulation of individual labyrinthine nerve branches with trains of single electrical pulses. The timing of the single pulses was adapted from spike discharge patterns of frog semicircular canal nerve afferents during sinusoidal head rotation. Because each electrical pulse evoked a single spike in afferent fibers, the resulting sequences with sinusoidally modulated intervals and peak frequencies up to 100 Hz allowed studying the processing of presynaptic afferent inputs with in vivo characteristics in second-order vestibular neurons recorded in vitro in an isolated whole brain. Variation of pulse-train parameters showed that the postsynaptic compound response dynamics differ in the two types of frog vestibular neurons. In tonic neurons, subthreshold compound responses and evoked discharge patterns exhibited relatively linear dynamics and were generally aligned with pulse frequency modulation. In contrast, compound responses of phasic neurons were asymmetric with large leads of subthreshold response peaks and evoked spike discharge relative to stimulus waveform. These nonlinearities were caused by the particular intrinsic properties of phasic vestibular neurons and were facilitated by GABAergic and glycinergic inhibitory inputs from tonic type vestibular interneurons and by cerebellar circuits. Coadapted intrinsic filter and emerging network properties thus form dynamically different neuronal elements that provide the appropriate cellular basis for a parallel processing of linear, tonic, and nonlinear phasic vestibulo-ocular response components in central vestibular neurons.

Central vestibular neurons process head movement-related sensory signals over a wide dynamic range. In the isolated frog whole brain, second-order vestibular neurons were identified by monosynaptic responses after electrical stimulation of individual semicircular canal nerve branches. Neurons were classified as tonic or phasic vestibular neurons based on their different discharge patterns in response to positive current steps. With increasing frequency of sinusoidally modulated current injections, up to 100 Hz, there was a concomitant decrease in the impedance of tonic vestibular neurons. Subthreshold responses as well as spike discharge showed classical low-pass filter-like characteristics with corner frequencies ranging from 5 to 20 Hz. In contrast, the impedance of phasic vestibular neurons was relatively constant over a wider range of frequencies or showed a resonance at ∼40 Hz. Above spike threshold, single spikes of phasic neurons were synchronized with the sinusoidal stimulation between ∼20 and 50 Hz, thus showing characteristic bandpass filter-like properties. Both the subthreshold resonance and bandpass filter-like discharge pattern depend on the activation of an I D potassium conductance. External current or synaptic stimulation that produced impedance increases (i.e., depolarization in tonic or hyperpolarization in phasic neurons) had opposite and complementary effects on the responses of the two types of neurons. Thus, membrane depolarization by current steps or repetitive synaptic excitation amplified synaptic inputs in tonic vestibular neurons and reduced them in phasic neurons. These differential, opposite membrane response properties render the two neuronal types particularly suitable for either integration (tonic neurons) or signal detection (phasic neurons), respectively, and dampens variations of the resting membrane potential in the latter.

Abbreviated title: Properties of lateral vestibular nucleus neurons This manuscript includes 2 tables and 6 figures. The abstract includes 250 words. ABSTRACT In vitro intracellular recordings of central vestibular neurons have been restricted so far to the medial vestibular nucleus (MVN). We performed intracellular recordings of large Deiters' neurons in the lateral vestibular nucleus (LVN) to determine their static and dynamic membrane properties, and compare them with those of type A and B neurons identified in the MVN. Unlike MVN neurons, the giant-sized LVN neurons form a homogeneous population of cells characterized by sharp spikes, a low-amplitude, biphasic after-hyperpolarization like type B MVN neurons, but also an Alike rectification like type A MVN neurons. In accordance with their lower membrane resistance, the sensitivity of LVN neurons to current injection was lower than that of MVN neurons over a large range of frequencies. The main difference between LVN and MVN neurons was that the Bode plots showing the sensitivity of LVN neurons as a function of stimulation frequency were flatter than those of MVN neurons, and displayed a weaker resonance. Furthermore, most LVN neurons did not show a gradual decrease of their firing rate modulation in the frequency range where it was observed in MVN neurons. LVN neurons synchronized their firing with the depolarizing phase of high-frequency sinusoidal current injections. In vivo studies have shown that the MVN would be mainly involved in gaze control, while the giant LVN neurons that project to the spinal cord are involved in the control of posture. We suggest that the difference in the membrane properties of LVN and MVN neurons may reflect their specific physiological roles.

To assess potential indices of nutritional condition, we examined changes in lipid content and the blood refractive index (BRI) of postlarval, juvenile and adult prawns (Penaeus spp.) that had been starved or fed to different levels of satiation. The whole-body lipid content (WBL) of small juvenile P. esculentus (20–120 mg wet weight) decreased significantly after 12 h of starvation. The WBL of postlarval P. monodon (4–10 mg wet weight) also decreased during starvation, with WBL almost halving after 5 days. Juvenile P. monodon (0.5–1.3 g wet weight) fed at 25 or 50% of the satiation ration for 6 days had significantly lower WBL than satiated prawns. The lowest concentrations of WBL were recorded for starved prawns and those fed to 25% of satiation. In larger juvenile P. semisulcatus (0.3–1.2 g wet weight) the WBL was also sensitive to starvation, declining significantly after only 1 day. The blood lipid content and digestive gland lipid of adult P. semisulcatus (28–43 g wet weight) decreased significantly after 4 days of starvation. The BRI of starved prawns and those fed to satiation correlated well with the WBL in the case of smaller prawns (r>0.96) and with the blood lipid of adult P. semisulcatus (28–43 g wet weight). However, there was a weaker correlation between BRI and WBL in prawns whose feed allocations were between starvation and satiation (r=0.86). These results from several prawn species and different size classes show that both the BRI and WBL have potential as indices of nutritional condition. Although BRI is much easier and cheaper to measure than WBL and can be measured in the field, it is suitable only for prawns from which sufficient blood can be obtained — generally those larger than 300 mg wet weight (7 mm carapace length). In contrast, WBL can be measured with a good level of precision in individual prawns as small as 20 mg wet weight (3 mm carapace length) using relatively simple laboratory equipment.

In this work, changes in the mechanical properties of carbon-carbon composites during processing are studied using nondestructive characterization techniques. Ultrasonics and radiography are used to measure the local stiffnesses in carbon-carbon panels after each stage in the processing cycle. The degree of material inhomogeneity (as measured by the standard deviation in the local moduli) was monitored throughout the fabrication process. The nondestructively measured stiffnesses were compared with direct mechanical measurements to assess the viability of the technique.