iTRVZ: liquid nano-platform for signal integration on the plasma membrane

Signalling is one of the most important functions of the cellular plasma membrane (PM). A variety of extracellular signalling molecules bind to their specific receptors in the PM, and the engaged receptors in turn trigger various cytoplasmic signalling cascades. These signalling pathways are intertwined and affect each other, in a process called crosstalk, which enables the cells to fine tune the overall signal. The crosstalk of different receptor signalling pathways has been examined quite extensively, but the platform responsible for signal integration has never been discovered. Here, using single-molecule imaging, we found a nanometer-scale (50-80 nm) liquid-like protein assembly on the PM cytoplasmic surface (at a density of ~2-μm apart from each other on average, with a lifetime of ~10 s), working as the signal transduction and integration platform for receptors, including GPI-anchored receptors (GPI-ARs), receptor-type tyrosine kinases (RTKs), and GPCRs. The platform consists of integrin, talin, RIAM, VASP, and zyxin, and is thus termed iTRVZ. These molecules are known as focal-adhesion constituents, but iTRVZ is distinct from focal adhesions, because iTRVZ exists on both the apical and basal PMs and lack vinculin. The iTRVZ formation is driven by specific protein-protein interactions, liquid-liquid phase separation, and interactions with actin filaments and raft domains via PI(4,5)P2. iTRVZ integrates and amplifies the GPI-AR and RTK signals in a strongly non-linear fashion, and thus works as an AND gate and noise filter. These findings greatly advance our understanding of the mechanism for crosstalk between signalling pathways.

Vasopressin resets the central circadian clock in a manner influenced by sex and vasoactive intestinal polypeptide signaling

Circadian rhythms in behavior and physiology are programmed by the suprachiasmatic nucleus (SCN) of the hypothalamus. A subset of SCN neurons produce the neuropeptide arginine vasopressin (AVP), but it remains unclear whether AVP signaling influences the SCN clock directly. Here we test that AVP signaling acting through V1A and V1B receptors influences molecular rhythms in SCN neurons. V1 receptor agonists were applied ex vivo to PERIOD2::LUCIFERASE SCN slices, allowing for real-time monitoring of changes in molecular clock function. V1A/B agonists reset the phase of the SCN molecular clock in a time-dependent manner, with larger magnitude responses by the female SCN. Further, we find evidence that both Gq and Gs signaling pathways interact with V1A/B-induced SCN resetting, and that this response requires vasoactive intestinal polypeptide (VIP) signaling. Collectively, this work indicates that AVP signaling resets SCN molecular rhythms in conjunction with VIP signaling and in a manner influenced by sex. This highlights the utility of studying clock function in both sexes and suggests that signal integration in central clock circuits regulates emergent properties important for the control of daily rhythms in behavior and physiology.

Contribution of linear and nonlinear mechanisms to predictive motion estimation

Successful behavior relies on the ability to use information obtained from past experience to predict what is likely to occur in the future. A salient example of predictive encoding comes from the vertebrate retina, where neural circuits encode information that can be used to estimate the trajectory of a moving object. Predictive computations should be a general property of sensory systems, but the features needed to identify these computations across neural systems are not well understood. Here, we identify several properties of predictive computations in the primate retina that likely generalize across sensory systems. These features include calculating the derivative of incoming signals, sparse signal integration, and delayed response suppression. These findings provide a deeper understanding of how the brain carries out predictive computations and identify features that can be used to recognize these computations throughout the brain.

Temporal Differences between Load and Movement Signal Integration in the Sensorimotor Network of an Insect Leg

Nervous systems face a torrent of sensory inputs, including proprioceptive feedback. Signal integration depends on spatially and temporally coinciding signals. It is unclear how relative time delays affect multimodal signal integration from spatially distant sense organs. We measured transmission times and latencies along all processing stages of sensorimotor pathways in the stick insect leg muscle control system using intra- and extracellular recordings. Transmission times of signals from load-sensing tibial and trochanterofemoral campaniform sensilla (tiCS, tr/fCS) to the premotor network were longer than from the movement-sensing femoral chordotonal organ (fCO). We characterized connectivity patterns from tiCS, tr/fCS, and fCO afferents to identified premotor nonspiking interneurons (NSIs) and motor neurons (MNs) by distinguishing short- and long-latency responses to sensory stimuli. Functional NSI connectivity depended on sensory context. The timeline of concurrent tiCS and fCO signals had an early phase of movement signal influences and delayed load influences. Temporal differences persisted into MN activity and muscle force development. We demonstrate a temporal difference in the processing of two distinct sensory modalities generated by the sensorimotor network and affecting motor output. The reported temporal differences in sensory processing and signal integration improve our understanding of sensory network computation and function in motor control.

Compensation of target signal migration in the multichannel matched filter

The study proposes a method of target range signal compensation within different pulse burst periods during in-period matched filtering. The proposed method allows to reduce losses in case of long-term signal integration. This is especially important for signals highly sensitive to Doppler frequency shift. In terms of this parameter, a multichannel configuration of the compression filter is a probable solution for such signals. Based on the example of a signal with non-linear frequency modulation and the results of simulation modelling, we analyse the effectiveness of migration compensation and give recommendations on channel multiplexing for the compression filter with an integrated migration compensator.

Effectiveness of target signal migration compensation at compression filter output

The paper describes a case study with the target moving at unknown radial velocity. Exemplified by the frequency modulation signal, the study presents the analysis of specific features of channel multiplexing for the target range migration compensator at the compression filter output within pulse burst periods. Channel multiplexing allows to reduces losses in case of long-term signal integration. The solution effectiveness is estimated and a method is proposed for compensator channel multiplexing ensuring protection against unwanted signal expansion.

Bioluminescence and Photoreception in Unicellular Organisms: Light-Signalling in a Bio-Communication Perspective

Bioluminescence, the emission of light catalysed by luciferases, has evolved in many taxa from bacteria to vertebrates and is predominant in the marine environment. It is now well established that in animals possessing a nervous system capable of integrating light stimuli, bioluminescence triggers various behavioural responses and plays a role in intra- or interspecific visual communication. The function of light emission in unicellular organisms is less clear and it is currently thought that it has evolved in an ecological framework, to be perceived by visual animals. For example, while it is thought that bioluminescence allows bacteria to be ingested by zooplankton or fish, providing them with favourable conditions for growth and dispersal, the luminous flashes emitted by dinoflagellates may have evolved as an anti-predation system against copepods. In this short review, we re-examine this paradigm in light of recent findings in microorganism photoreception, signal integration and complex behaviours. Numerous studies show that on the one hand, bacteria and protists, whether autotrophs or heterotrophs, possess a variety of photoreceptors capable of perceiving and integrating light stimuli of different wavelengths. Single-cell light-perception produces responses ranging from phototaxis to more complex behaviours. On the other hand, there is growing evidence that unicellular prokaryotes and eukaryotes can perform complex tasks ranging from habituation and decision-making to associative learning, despite lacking a nervous system. Here, we focus our analysis on two taxa, bacteria and dinoflagellates, whose bioluminescence is well studied. We propose the hypothesis that similar to visual animals, the interplay between light-emission and reception could play multiple roles in intra- and interspecific communication and participate in complex behaviour in the unicellular world.

Computer Simulation of a Surface Charge Nanobiosensor with Internal Signal Integration

The ionized states of molecular analytes located on solid surfaces require profound investigation and better understanding for applications in the basic sciences in general, and in the design of nanobiosensors, in particular. Such ionized states are induced by the interactions of molecules between them in the analyzed substance and with the target surface. Here, computer simulations using COMSOL Multiphysics software show the effect of surface charge density and distribution on the output generation in a dynamic PIN diode with gate control. This device, having built-in potential barriers, has a unique internal integration of output signal generation. The identified interactions showed the possibility of a new design for implementing a nanobiosensor based on a dynamic PIN diode in a mode with surface charge control.