INTEGRATION OF POSITIVE AND NEGATIVE FEEDBACK LOOPS IN A CRAYFISH MUSCLE

1994 ◽  
Vol 187 (1) ◽  
pp. 305-313
Author(s):  
P Skorupski ◽  
P Vescovi ◽  
B Bush
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Motor Neurone ◽  
Chordotonal Organ ◽  
Negative Feedback Loops ◽  
Reflex Pathways ◽  
Motor Neurones ◽  
Receptor Organ ◽  
Group 2

It is now well established that in arthropods movement-related feedback may produce positive, as well as negative, feedback reflexes (Bassler, 1976; DiCaprio and Clarac, 1981; Skorupski and Sillar, 1986; Skorupski et al. 1992; Vedel, 1980; Zill, 1985). Usually the same motor neurones are involved in both negative feedback (resistance) reflex responses and positive feedback reflexes. Reflex reversal involves a shift in the pattern of central inputs to a motor neurone, for example from excitation to inhibition. In the crayfish, central modulation of reflexes has been described in some detail for two basal limb proprioceptors, the thoracocoxal muscle receptor organ (TCMRO) and the thoracocoxal chordotonal organ (TCCO) (Skorupski et al. 1992; Skorupski and Bush, 1992). Leg promotor motor neurones are excited by stretch of the TCMRO (which, in vivo, occurs on leg remotion) in a negative feedback reflex, but when this reflex reverses they are inhibited by the same stimulus. Release of the TCCO (which corresponds to leg promotion) excites some, but not all, promotor motor neurones in a positive feedback reflex. There are at least two ways in which the reflex control of a muscle may be modulated in this system. Firstly, inputs to motor neurones may be routed via alternative reflex pathways to produce different reflex outputs. Secondly, the pattern of inputs to a motor pool may be inhomogeneous, so that activation of different subgroups of the motor pool causes different outputs. Different crayfish promotor motor neurones are involved in different reflexes. On this basis, the motor neurones may be classified into at least two subgroups: those that are excited by the TCCO in a positive feedback reflex (group 1) and those that are not (group 2). Do these motor neurone subgroups have different effects on the promotor muscle, or is the output of the two promotor subgroups summed at the neuromuscular level? To address this question we recorded from the promotor nerve and muscle in a semi-intact preparation of the crayfish, Pacifastacus leniusculus. Adult male and female crayfish, 8-11 cm rostrum to tail, were decapitated and the tail, carapace and viscera removed. The sternal artery was cannulated and perfused with oxygenated crayfish saline, as described previously (Sillar and Skorupski, 1986).

Phase-dependent reversal of reflexes mediated by the thoracocoxal muscle receptor organ in the crayfish, Pacifastacus leniusculus

1986 ◽  
Vol 55 (4) ◽  
pp. 689-695 ◽  
Author(s):  
P. Skorupski ◽  
K. T. Sillar
Keyword(s):  
Motor Neurons ◽  
Negative Feedback ◽  
Positive Feedback ◽  
Motor Output ◽  
Dependent Manner ◽  
Muscle Receptor ◽  
Reflex Pathways ◽  
Receptor Organ ◽  
Positive And Negative Feedback ◽  
Central Excitability

Both negative feedback, resistance reflexes and positive feedback, assistance reflexes are mediated by the thoracocoxal muscle receptor organ (TCMRO) in the crayfish, depending on the central excitability of the preparation. In this paper we present evidence that the velocity-sensitive afferent T fiber of the TCMRO may elicit either resistance or assistance reflexes in different preparations. In preparations displaying assistance reflexes, the S and T fibers of the TCMRO exert reciprocal effects on leg motor neurons (MNs). The S fiber excites promotor MNs (negative feedback) and inhibits remotor MNs, the T fiber excites remotor MNs (positive feedback) and inhibits promotor MNs. During reciprocal motor output of promotor and remotor MNs, reflexes mediated by the TCMRO are modulated in a phase-dependent manner. The TCMRO excites promotor MNs during their active phases (negative feedback) but inhibits them during their reciprocal phases. Remotor MNs are excited by the TCMRO during their active phases (positive feedback). It is proposed that depolarizing central inputs that occur in the S and T fibers at opposite phases of the motor output cycle (21) facilitate the output effects of each afferent in alternation, effectively mediating a phase-dependent shift between the effects of one afferent and the other. The implications of central modulation of reflex pathways and the possible functions of positive and negative feedback reflexes during locomotion are discussed.

Peripheral control of the gain of a central synaptic connection between antagonistic motor neurones in the locust

1996 ◽  
Vol 199 (3) ◽  
pp. 613-625
Author(s):  
T Jellema ◽  
W Heitler
Keyword(s):  
Muscle Contraction ◽  
Sensory Input ◽  
Sense Organ ◽  
Gain Control ◽  
Motor Neurone ◽  
Extensor Muscle ◽  
Chordotonal Organ ◽  
Excitatory Postsynaptic Potential ◽  
Motor Neurones ◽  
Peripheral Sensory

The metathoracic fast extensor tibiae (FETi) motor neurone of locusts is unusual amongst insect motor neurones because it makes output connections within the central nervous system as well as in the periphery. It makes excitatory chemical synaptic connections to most if not all of the antagonist flexor tibiae motor neurones. The gain of the FETi-flexor connection is dependent on the peripheral conditions at the time of the FETi spike. This dependency has two aspects. First, sensory input resulting from the extensor muscle contraction can sum with the central excitatory postsynaptic potential (EPSP) to augment its falling phase if the tibia is restrained in the flexed position (initiating a tension-dependent reflex) or is free to extend (initiating a movement-dependent resistance reflex). This effect is thus due to simple postsynaptic summation of the central EPSP with peripheral sensory input. Second, the static tibial position at the time of the FETi spike can change the amplitude of the central EPSP, in the absence of any extensor muscle contraction. The EPSP can be up to 30 % greater in amplitude if FETi spikes with the tibia held flexed rather than extended. The primary sense organ mediating this effect is the femoral chordotonal organ. Evidence is presented suggesting that the mechanism underlying this change in gain may be specifically localised to the FETi-flexor connection, rather than being due to general position-dependent sensory feedback summing with the EPSP. The change in the amplitude of the central EPSP is probably not caused by general postsynaptic summation with tonic sensory input, since a diminution in the amplitude of the central EPSP caused by tibial extension is often accompanied by overall tonic excitation of the flexor motor neurone. Small but significant changes in the peak amplitude of the FETi spike have a positive correlation with changes in the EPSP amplitude, suggesting a likely presynaptic component to the mechanism of gain control. The change in amplitude of the EPSP can alter its effectiveness in producing flexor motor output and, thus, has functional significance. The change serves to augment the effectiveness of the FETi-flexor connection when the tibia is fully flexed, and thus to increase its adaptive advantage during the co-contraction preceding a jump or kick, and to reduce the effectiveness of the connection when the tibia is partially or fully extended, and thus to reduce its potentially maladaptive consequences during voluntary extension movements such as thrusting.

The principle of homeostasis in the hypothalamus-pituitary-adrenal system: new insight from positive feedback

2007 ◽  
Vol 293 (1) ◽  
pp. R83-R98 ◽  
Author(s):  
A. Peters ◽  
M. Conrad ◽  
C. Hubold ◽  
U. Schweiger ◽  
B. Fischer ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Glucocorticoid Receptors ◽  
Current Knowledge ◽  
Biological Systems ◽  
Feedback Loops ◽  
Endocrine Disorders ◽  
Negative Feedback Loops ◽  
Adrenal System ◽  
Positive And Negative Feedback

Feedback control, both negative and positive, is a fundamental feature of biological systems. Some of these systems strive to achieve a state of equilibrium or “homeostasis”. The major endocrine systems are regulated by negative feedback, a process believed to maintain hormonal levels within a relatively narrow range. Positive feedback is often thought to have a destabilizing effect. Here, we present a “principle of homeostasis,” which makes use of both positive and negative feedback loops. To test the hypothesis that this homeostatic concept is valid for the regulation of cortisol, we assessed experimental data in humans with different conditions (gender, obesity, endocrine disorders, medication) and analyzed these data by a novel computational approach. We showed that all obtained data sets were in agreement with the presented concept of homeostasis in the hypothalamus-pituitary-adrenal axis. According to this concept, a homeostatic system can stabilize itself with the help of a positive feedback loop. The brain mineralocorticoid and glucocorticoid receptors—with their known characteristics—fulfill the key functions in the homeostatic concept: binding cortisol with high and low affinities, acting in opposing manners, and mediating feedback effects on cortisol. This study supports the interaction between positive and negative feedback loops in the hypothalamus-pituitary-adrenal system and in this way sheds new light on the function of dual receptor regulation. Current knowledge suggests that this principle of homeostasis could also apply to other biological systems.

scholarly journals Positive Feedback Promotes Oscillations in Negative Feedback Loops

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e104761 ◽  
Author(s):  
Bharath Ananthasubramaniam ◽  
Hanspeter Herzel
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Feedback Loops ◽  
Negative Feedback Loops

scholarly journals The Inherent Walking Direction Differs for the Prothoracic and Metathoracic Legs of Stick Insects

1985 ◽  
Vol 116 (1) ◽  
pp. 301-311 ◽  
Author(s):  
ULRICH BÄSSLER ◽  
EVA FOTH ◽  
GERHARD BREUTEL
Keyword(s):  
Positive Feedback ◽  
Stick Insect ◽  
Chordotonal Organ ◽  
Suboesophageal Ganglion ◽  
Stick Insects ◽  
Motor Neurones ◽  
Direction Of Movement ◽  
Slippery Surface

On a slippery surface the forelegs of a decapitated stick insect walk forwards and the hindlegs, backwards. Animals with only forelegs but that are otherwise intact walk forwards, whereas animals with only hindlegs walk mostly backwards. Usually when intact animals start to walk, their hindlegs exert a rearwards thrust on the substrate, but occasionally the starting forces are directed forwards. A rampwise extension of the femoral chordotonal organ in the fixed foreleg of a walking animal first excites the flexor tibiae muscle (positive feedback). Towards the end of the ramp stimulus the activity of the flexor decreases, and the extensor tibiae motor neurones become strongly active. All experiments indicated that the inherent direction of movement of the metathorax is rearwards. In intact animals there must be a coordinating pathway from the prothorax to the metathorax that, together with the suboesophageal ganglion, induces the hindlegs to walk forwards.

scholarly journals A synthetic gene circuit for measuring autoregulatory feedback control.

2015 ◽  
Author(s):  
Miquel Angel Schikora-Tamarit ◽  
Carlos Toscano-Ochoa ◽  
Julia Domingo Espinos ◽  
Lorena Espinar ◽  
Lucas Carey
Keyword(s):  
High Throughput ◽  
Negative Feedback ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Feedback Regulation ◽  
Feedback Loops ◽  
Expression Noise ◽  
Negative Feedback Loops

Auto regulatory feedback loops occur in the regulation of molecules ranging from ATP to MAP kinases to zinc. Negative feedback loops can increase a system′s robustness, while positive feedback loops can mediate transitions between cell states. Recent genome-wide experimental and computational studies predict hundreds of novel feedback loops. However, not all physical interactions are regulatory, and many experimental methods cannot detect self-interactions. Our understanding of regulatory feedback loops is therefore hampered by the lack of high-throughput methods to experimentally quantify the presence, strength, and temporal dynamics of auto regulatory feedback loops. Here we present a mathematical and experimental framework for high-throughput quantification of feedback regulation, and apply it to RNA binding proteins (RBPs) in yeast. Our method is able to determine the existence of both direct and indirect positive and negative feedback loops, and to quantify the strength of these loops. We experimentally validate our model using two RBPs which lack native feedback loops, and by the introduction of synthetic feedback loops. We find that the the RBP Puf3 does not natively participate in any direct or indirect feedback regulation, but that replacing the native 3′UTR with that of COX17 generates an auto-regulatory negative feedback loop which reduces gene expression noise. Likewise, the RBP Pub1 does not natively participate in any feedback loops, but a synthetic positive feedback loop involving Pub1 results in increased expression noise. Our results demonstrate a synthetic experimental system for quantifying the existence and strength of feedback loops using a combination of high-throughput experiments and mathematical modeling. This system will be of great use in measuring auto-regulatory feedback by RNA binding proteins, a regulatory motif that is difficult to quantify using existing high-throughput methods.

scholarly journals Overlaid positive and negative feedback loops shape dynamical properties of PhoPQ two-component system

2021 ◽  
Vol 17 (1) ◽  
pp. e1008130
Author(s):  
Satyajit D Rao ◽  
Oleg A Igoshin
Keyword(s):  
Steady State ◽  
Negative Feedback ◽  
Positive Feedback ◽  
Feedback Loops ◽  
General Mechanism ◽  
Response Dynamics ◽  
Negative Feedback Loops ◽  
Two Component ◽  
Positive And Negative Feedback ◽  
Dynamical Properties

Bacteria use two-component systems (TCSs) to sense environmental conditions and change gene expression in response to those conditions. To amplify cellular responses, many bacterial TCSs are under positive feedback control, i.e. increase their expression when activated. Escherichia coli Mg2+ -sensing TCS, PhoPQ, in addition to the positive feedback, includes a negative feedback loop via the upregulation of the MgrB protein that inhibits PhoQ. How the interplay of these feedback loops shapes steady-state and dynamical responses of PhoPQ TCS to change in Mg2+ remains poorly understood. In particular, how the presence of MgrB feedback affects the robustness of PhoPQ response to overexpression of TCS is unclear. It is also unclear why the steady-state response to decreasing Mg2+ is biphasic, i.e. plateaus over a range of Mg2+ concentrations, and then increases again at growth-limiting Mg2+. In this study, we use mathematical modeling to identify potential mechanisms behind these experimentally observed dynamical properties. The results make experimentally testable predictions for the regime with response robustness and propose a novel explanation of biphasic response constraining the mechanisms for modulation of PhoQ activity by Mg2+ and MgrB. Finally, we show how the interplay of positive and negative feedback loops affects the network’s steady-state sensitivity and response dynamics. In the absence of MgrB feedback, the model predicts oscillations thereby suggesting a general mechanism of oscillatory or pulsatile dynamics in autoregulated TCSs. These results improve the understanding of TCS signaling and other networks with overlaid positive and negative feedback.

scholarly journals Central Synaptic Coupling of Walking Leg Motor Neurones in the Crayfish: Implications for Sensorimotor Integration

1988 ◽  
Vol 140 (1) ◽  
pp. 355-379
Author(s):  
PETER SKORUPSKI ◽  
KEITH T. SILLAR
Keyword(s):  
Motor Control ◽  
Sensorimotor Integration ◽  
Afferent Input ◽  
Stretch Receptor ◽  
Motor Neurone ◽  
Synaptic Coupling ◽  
Muscle Receptor ◽  
Motor Neurones ◽  
Receptor Organ ◽  
Inhibitory Interactions

We present electrophysiological evidence for the presence of central output synapses on crayfish walking leg motor neurones. The effect of these central outputs is that a motor neurone can exert tonic graded control over other motor neurones without the requirement for spiking. Excitatory interactions among synergists and inhibitory interactions among antagonists are described. This central coupling among leg motor neurones profoundly affects their responses to afferent input from an identified stretch receptor, the thoracocoxal muscle receptor organ (TCMRO). Injecting current into a motor neurone can change the gain of TCMRO reflexes in other motor neurones. Some motor neurones are also capable of reversing the sign of TCMRO reflexes by inhibiting reflex firing of antagonists and facilitating reflex activity in synergists. The implications of these central interactions of motor neurones in motor control are discussed.

scholarly journals Interplay of positive and negative feedback loops governs robustness in multistable biological networks

2021 ◽  
Author(s):  
Anish Hebbar ◽  
Ankush Moger ◽  
Kishore Hari ◽  
Mohit Kumar Jolly
Keyword(s):  
Negative Feedback ◽  
Network Topology ◽  
Positive Feedback ◽  
Biological Networks ◽  
Continuous Model ◽  
Feedback Loops ◽  
Large Networks ◽  
Structural Robustness ◽  
Negative Feedback Loops ◽  
Positive And Negative Feedback

Biological networks are widely reported to be robust to both external and internal perturbations. However, the exact mechanisms and design principles that enable robustness are not yet fully understood. Here we investigated dynamic and structural robustness in biological networks with regards to phenotypic distribution and plasticity. We use two different approaches to simulate these networks: a computationally inexpensive, parameter-independent continuous model, and an ODE-based parameter-agnostic framework (RACIPE), both of which yield similar phenotypic distributions. Using perturbations to network topology and by varying network parameters, we show that multistable biological networks are structurally and dynamically more robust as compared to their randomized counterparts. These features of robustness are governed by an interplay of positive and negative feedback loops embedded in these networks. Using a combination of the number of negative and positive feedback loops weighted by their lengths and sign, we identified a metric that can explain the structural and dynamical robustness of these networks. This metric enabled us to compare networks across multiple sizes, and the network principles thus obtained can be used to identify fragilities in large networks without simulating their dynamics. Our analysis highlights a network topology based approach to quantify robustness in multistable biological networks.

scholarly journals Positive And Negative Feedback Loops Coupled By Common Transcription Activator And Repressor

2015 ◽  
Vol 69 (1) ◽  
Author(s):  
Jan Sielewiesiuk ◽  
Agata Łopaciuk
Keyword(s):  
Negative Feedback ◽  
Positive Feedback ◽  
Numerical Solutions ◽  
Transcription Activator ◽  
Negative Feedback Loops ◽  
Enzymatic Regulation ◽  
Regulation Network ◽  
Positive And Negative Feedback ◽  
The Difference ◽  
Analysis Of Stability

AbstractDynamical systems consisting of two interlocked loops with negative and positive feedback have been studied using the linear analysis of stability and numerical solutions. Conditions for saddle-node bifurcation were formulated in a general form. Conditions for Hopf bifurcations were found in a few symmetrical cases. Auto-oscillations, when they exist, are generated by the negative feedback repressive loop. This loop determines the frequency and amplitude of oscillations. The positive feedback loop of activation slightly modifies the oscillations. Oscillations are possible when the difference between Hilll’s coefficients of the repression and activation is sufficiently high. The highly cooperative activation loop with a fast turnover slows down or even makes the oscillations impossible. The system under consideration can constitute a component of epigenetic or enzymatic regulation network.

Sign in / Sign up

Export Citation Format

Share Document