scholarly journals A GPCR negative feedback loop underlies efficient coding of external stimuli

2020 ◽  
Author(s):  
Rotem Ruach ◽  
Shai Yellinek ◽  
Eyal Itskovits ◽  
Alon Zaslaver
Keyword(s):  
Sensory Neurons ◽  
Negative Feedback ◽  
Feedback Inhibition ◽  
Essential Feature ◽  
Relevant Information ◽  
Complex Stimulus ◽  
Response Dynamics ◽  
Calcium Dependent ◽  
Spatio Temporal ◽  
External Stimuli

AbstractEfficient navigation based on chemical cues is an essential feature shared by all animals. These cues may be encountered in complex spatio-temporal patterns and with orders of magnitude varying intensities. Nevertheless, sensory neurons accurately extract the relevant information from such perplexing signals. Here, we show how a single sensory neuron in C. elegans worms can cell-autonomously encode complex stimulus patterns composed of instantaneous sharp changes and of slowly-changing continuous gradients. This encoding relies on a simple negative feedback in the GPCR signaling pathway in which TAX-6/Calcineurin plays a key role in mediating the feedback inhibition. Crucially, this negative feedback pathway supports several important coding features that underlie an efficient navigation strategy, including exact adaptation and adaptation to the magnitude of the gradient’s first derivative. A simple mathematical model accurately captured the fine neural dynamics of both wt and tax-6 mutant animals, further highlighting how the calcium-dependent activity of TAX-6/Calcineurin dictates GPCR inhibition and response dynamics. As GPCRs are ubiquitously expressed in all sensory neurons, this mechanism may be a universal solution for efficient cell-autonomous coding of external stimuli.

scholarly journals Linear Response of General Observables in Spiking Neuronal Network Models

Entropy ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 155
Author(s):  
Bruno Cessac ◽  
Ignacio Ampuero ◽  
Rodrigo Cofré
Keyword(s):  
Linear Response ◽  
Network Connectivity ◽  
Network Models ◽  
General Context ◽  
Collective Effect ◽  
Neuronal Dynamics ◽  
The Past ◽  
Spatio Temporal ◽  
External Stimuli ◽  
Spike Dynamics

We establish a general linear response relation for spiking neuronal networks, based on chains with unbounded memory. This relation allow us to predict the influence of a weak amplitude time dependent external stimuli on spatio-temporal spike correlations, from the spontaneous statistics (without stimulus) in a general context where the memory in spike dynamics can extend arbitrarily far in the past. Using this approach, we show how the linear response is explicitly related to the collective effect of the stimuli, intrinsic neuronal dynamics, and network connectivity on spike train statistics. We illustrate our results with numerical simulations performed over a discrete time integrate and fire model.

scholarly journals Adhesion molecules during somitogenesis in the avian embryo.

1987 ◽  
Vol 104 (5) ◽  
pp. 1361-1374 ◽  
Author(s):  
J L Duband ◽  
S Dufour ◽  
K Hatta ◽  
M Takeichi ◽  
G M Edelman ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Tissue Remodeling ◽  
Cell Aggregation ◽  
Avian Embryo ◽  
Primary Role ◽  
Calcium Dependent ◽  
Tissue Dissociation ◽  
Spatio Temporal

In avian embryos, somites constitute the morphological unit of the metameric pattern. Somites are epithelia formed from a mesenchyme, the segmental plate, and are subsequently reorganized into dermatome, myotome, and sclerotome. In this study, we used somitogenesis as a basis to examine tissue remodeling during early vertebrate morphogenesis. Particular emphasis was put on the distribution and possible complementary roles of adhesion-promoting molecules, neural cell adhesion molecule (N-CAM), N-cadherin, fibronectin, and laminin. Both segmental plate and somitic cells exhibited in vitro calcium-dependent and calcium-independent systems of cell aggregation that could be inhibited respectively by anti-N-cadherin and anti-N-CAM antibodies. In vivo, the spatio-temporal expression of N-cadherin was closely associated with both the formation and local disruption of the somites. In contrast, changes in the prevalence of N-CAM did not strictly accompany the remodeling of the somitic epithelium into dermamyotome and sclerotome. It was also observed that fibronectin and laminin were reorganized secondarily in the extracellular spaces after CAM-mediated contacts were modulated. In an in vitro culture system of somites, N-cadherin was lost on individual cells released from somite explants and was reexpressed when these cells reached confluence and established intercellular contacts. In an assay of tissue dissociation in vitro, antibodies to N-cadherin or medium devoid of calcium strongly and reversibly dissociated explants of segmental plates and somites. Antibodies to N-CAM exhibited a smaller disrupting effect only on segmental plate explants. In contrast, antibodies to fibronectin and laminin did not perturb the cohesion of cells within the explants. These results emphasize the possible role of cell surface modulation of CAMs during the formation and remodeling of some transient embryonic epithelia. It is suggested that N-cadherin plays a major role in the control of tissue remodeling, a process in which N-CAM is also involved but to a lesser extent. The substratum adhesion molecules, fibronectin and laminin, do not appear to play a primary role in the regulation of these processes but may participate in cell positioning and in the stabilization of the epithelial structures.

Multimedia Databases and Data Management

2012 ◽  
pp. 1-11
Author(s):  
Shu-Ching Chen
Keyword(s):  
Data Management ◽  
Relevant Information ◽  
Multimedia Databases ◽  
Multimedia Data ◽  
Formal Structure ◽  
Multimedia Database ◽  
Storage Devices ◽  
Temporal Relationships ◽  
Spatio Temporal ◽  
Application Requirements

The exponential growth of the technological advancements has resulted in high-resolution devices, such as digital cameras, scanners, monitors, and printers, which enable the capturing and displaying of multimedia data in high-density storage devices. Furthermore, more and more applications need to live with multimedia data. However, the gap between the characteristics of various media types and the application requirements has created the need to develop advanced techniques for multimedia data management and the extraction of relevant information from multimedia databases. Though many research efforts have been devoted to the areas of multimedia databases and data management, it is still far from maturity. The purpose of this article is to discuss how the existing techniques, methodologies, and tools addressed relevant issues and challenges to enable a better understanding in multimedia databases and data management. The focuses include: (1) how to develop a formal structure that can be used to capture the distinguishing content of the media data in a multimedia database (MMDB) and to form an abstract space for the data to be queried; (2) how to develop advanced content analysis and retrieval techniques that can be used to bridge the gaps between the semantic meaning and low-level media characteristics to improve multimedia information retrieval; and (3) how to develop query mechanisms that can handle complex spatial, temporal, and/or spatio-temporal relationships of multimedia data to answer the imprecise and incomplete queries issued to an MMDB.

Diffusion, Buffering, and Binding

1998 ◽  
Author(s):  
Christof Koch
Keyword(s):  
Synaptic Plasticity ◽  
Intracellular Calcium ◽  
Temporal Dynamics ◽  
Critical Concentration ◽  
Two Photon Microscopy ◽  
Calcium Dependent ◽  
Calcium Sensors ◽  
Free Intracellular Calcium ◽  
Messenger Molecules ◽  
Spatio Temporal

In Chap. 9 we introduced calcium ions and alluded to their crucial role in regulating the day-to-day life of neurons. The dynamics of the free intracellular calcium is controlled by a number of physical and chemical processes, foremost among them diffusion and binding to a host of different proteins, which serve as calcium buffers and as calcium sensors or triggers. Whereas buffers simply bind Ca2+ above some critical concentration, releasing it back into the cytoplasm when [Ca2+]i has been reduced below this level, certain proteins— such as calmodulin—change their conformation when they bind with Ca2+ ions, thereby activating or modulating enzymes, ionic channels, or other proteins. The calcium concentration inside the cell not only determines the degree of activation of calcium-dependent potassium currents but—much more importantly—is relevant for determining the changes in structure expressed in synaptic plasticity. As discussed in Chap. 13, it is these changes that are thought to underlie learning. Given the relevance of second messenger molecules, such as Ca2+, IP3, cyclic AMP and others, for the processes underlying growth, sensory adaptation, and the establishment and maintenance of synaptic plasticity, it is crucial that we have some understanding of the role that diffusion and chemical kinetics play in governing the behavior of these substances. Today, we have unprecedented access to the spatio-temporal dynamics of intracellular calcium in individual neurons using fluorescent calcium dyes, such as fura-2 or fluo-3, in combination with confocal or two-photon microscopy in the visible or in the infrared spectrum (Tsien, 1988; Tank et al., 1988; Hernández-Cruz, Sala, and Adams, 1990; Ghosh and Greenberg, 1995).

2. Negative feedback inhibition – Fundamental biological regulation in cells and organisms

2015 ◽  
Author(s):  
Jakub Wach ◽  
Marian Bubak ◽  
Piotr Nowakowski ◽  
Irena Roterman ◽  
Leszek Konieczny ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Feedback Inhibition ◽  
Biological Regulation ◽  
In Cells

Role of facilitated diffusion of calcium by calbindin in intestinal calcium absorption

1992 ◽  
Vol 262 (2) ◽  
pp. C517-C526 ◽  
Author(s):  
J. J. Feher ◽  
C. S. Fullmer ◽  
R. H. Wasserman
Keyword(s):  
Negative Feedback ◽  
Calcium Absorption ◽  
Feedback Inhibition ◽  
Basolateral Membrane ◽  
Reaction Diffusion ◽  
Diffusion Problem ◽  
Facilitated Diffusion ◽  
Calbindin D9k ◽  
And Diffusion

Computer simulations of transcellular Ca2+ transport in enterocytes were carried out using the simulation program SPICE. The program incorporated a negative-feedback entry of Ca2+ at the brush-border membrane that was characterized by an inhibitor constant of 0.5 microM cytosolic Ca2+ concentration ([Ca2+]). The basolateral Ca(2+)-ATPase was simulated by a four-step mechanism that resulted in Michaelis-Menten kinetics with a Michaelis constant of 0.24 microM [Ca2+]. The cytosolic diffusion of Ca2+ was simulated by dividing the cytosol into 10 slabs of equal width. Ca2+ binding to calbindin-D9K was simulated in each slab, and diffusion of free Ca2+, free calbindin, and Ca(2+)-laden calbindin was simulated between each slab. The cytosolic [Ca2+] of the simulated cells was regulated within the physiological range. Calbindin-D9K reduced the cytosolic [Ca2+] gradient, increased Ca2+ entry into the cell by removing the negative-feedback inhibition of Ca2+ entry, increased cytosolic Ca2+ flow, and increased the efflux of Ca2+ across the basolateral membrane by increasing the free [Ca2+] immediately adjacent to the pump. The enhancement of transcellular Ca2+ transport was nearly linearly dependent on calbindin-D9K concentration. The values of the dissociation constant (Kd) for calbindin-D9K were previously obtained experimentally in the presence and absence of KCl. Calbindin with the Kd obtained in the presence of KCl enhanced the simulated Ca2+ transport more than with the Kd obtained in the absence of KCl. This result suggests that the physiological Kd of calbindin is optimal for the enhancement of transcellular Ca2+ transport. The simulated Ca2+ flow was less than that predicted from the "near-equilibrium" analytic solution of the reaction-diffusion problem.

Sensitization of the gill and siphon withdrawal reflex of Aplysia: multiple sites of change in the neuronal network

1993 ◽  
Vol 70 (3) ◽  
pp. 1210-1220 ◽  
Author(s):  
L. E. Trudeau ◽  
V. F. Castellucci
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Neuronal Network ◽  
Feedback Inhibition ◽  
Excitatory Input ◽  
Major Mechanism ◽  
Withdrawal Reflex ◽  
The Difference ◽  
Central Synapses

1. Recent studies have emphasized the major contribution of interneuronal transmission to the mediation and learning-associated modulation of the gill and siphon withdrawal (GSW) reflex of Aplysia. We wish to provide more direct support for the hypothesis that inhibitory junctions are crucial sites of plasticity. 2. In parallel experiments we investigated modulation at five major sites of synaptic transmission in the GSW network: 1) from sensory neurons to motor neurons, 2) from sensory neurons to excitatory interneurons (INTs+) 3) from INTs+ to motor neurons (MNs), 4) from inhibitory interneurons (INTs-) to INTs+, and 5) from INTs+ to INTs-. 3. While recording simultaneously from a single sensory neuron of the LE cluster, an INT+, and a MN, we found that both LE-MN and LE-INTs+ synapses were facilitated by the activation of modulator neurons by stimulation of the left pleuroabdominal connective (185 and 93%, respectively) as well as by serotonin (5-HT) (191 and 84%). Junctions of the second type were therefore less facilitated. The difference in the magnitude of facilitation at these two sites is an indication of a branch-specific, differential efficacy in the modulation of different central synapses made by a single neuron. 4. Although INT(+)-MN junctions have the capacity to display marked posttetanic potentiation, they are not significantly potentiated after connective stimulation. Sensitization of the GSW reflex is therefore not necessarily accompanied by a modification of transmission at these synapses. 5. Inhibitory transmission to INTs+ is significantly reduced by connective stimulation (36%) and by 5-HT (71%). This supports the hypothesis that a reduction of feedback inhibition into INTs+ is a major mechanism of reflex sensitization and may account for the increased evoked firing of INTs+ that is observed after connective stimulation. 6. The excitatory input to INTs- is selectively decreased by 5-HT (50%) and by the molluscan neuropeptide small cardioactive peptide B (38%). This latter effect, which could produce disinhibition of INTs+, may explain the previous observation that this peptide is able to potentiate the evoked input to MNs of the reflex at a concentration (1 microM) that fails to modify monosynaptic sensory-motor transmission. 7. These results indicate that transmission through a small neuronal network that mediates a withdrawal reflex in Aplysia may be modulated at multiple sites and by different mechanisms. These mechanisms include: 1) branch-specific facilitation of sensory neuron outputs and 2) inhibition of INT(-)-INT+ inhibitory postsynaptic potentials by endogenous modulatory neurons and by 5-HT.(ABSTRACT TRUNCATED AT 400 WORDS)

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