bioRxiv Science⌕ Search

Biology subjects

Marder, E.

Publications and source records attributed to Marder, E..

At least 19 recordsLinked to original sources

Robustness tuning: mechanisms of acclimation-driven plasticity in a central pattern generator

Temperature influences neuronal and circuit output and extreme temperatures can disrupt neuronal performance. Acclimation invokes a form of neuronal plasticity that we call robustness tuning, that preserves nervous system performance during seasonal alterations in environmental conditions. The stomatogastric nervous system (STNS) of the American lobster, Homarus americanus, produces stereotyped rhythmic motor patterns that are maintained over a range of acute temperature changes, but lost under more extreme conditions. In the wild, H. americanus experience water temperatures from [~]2{degrees}C to 25{degrees}C during the course of a year. We acclimated lobsters to 18{degrees}C versus 4{degrees}C for [~]3 weeks, and found that the pyloric rhythm from warm-acclimated animals maintained its characteristic properties over an extended temperature range, when compared to those recorded from cold-acclimated animals. There were acclimation and temperature dependent differences in the responses of pyloric neurons to the neuropeptide, Crustacean Cardioactive Peptide (CCAP). Computational models suggest that pyloric neuron morphology and neuromodulator conductance distribution play a role in robustness tuning, the reversible changes that allow animals to repeatedly adapt to seasonal change.

neuroscience↗

Compensation of the effects of temperature on a motor system in the crab, Cancer borealis

Rising ocean temperatures challenge ectothermic animals to maintain essential behaviors such as movement and feeding. We asked how a complete neuromuscular pathway preserves function when every component process responds differently to warming. In the pyloric system of the crab Cancer borealis, we simultaneously recorded motor nerve activity, muscle membrane potential, and contraction. Warming preserved rhythmic nerve activity and excitatory junctional potentials, but contraction declined and failed first. Fixed low-frequency stimulation, mimicking cold-temperature motor output, resulted in reduced contraction at warm temperatures, whereas higher-frequency stimulation, mimicking warm-temperature motor output, partially restored contraction. Warming hyperpolarized muscle fibers, moving them farther from contraction threshold, but also reduced input resistance, which together limited over-excitability. However, high-potassium stimulation revealed that the muscle contractile machinery remained functional. Thus, warming acts differently across levels, and overlapping compensatory mechanisms help preserve neuromuscular function across a wide range of temperatures. Significance statementCold-blooded animals that live in climates with significant seasonal changes in ambient temperature must have myriad mechanisms to function over a wide range of environmental conditions. We explore the effects of temperature at multiple levels of organization within the stomatogastric system of the crab, Cancer borealis. We find a series of compensatory mechanisms that cooperatively help maintain stable function despite the fact that the motor patterns, neuromuscular junctions and muscle functions are all differently temperature dependent.

neuroscience↗

Quantitative Neuropeptidomics Reveals Thermal Acclimation-Induced Remodeling of Peptidergic Signaling in the American Lobster Homarus americanus

Global warming and rising ocean temperatures pose substantial challenges to marine ecosystems and crustacean populations. As an ectothermic species, the American lobster (Homarus americanus) relies on physiological and neurochemical mechanisms to maintain homeostasis under varying environmental conditions. To elucidate the role of neuropeptides in neuronal plasticity and systemic adaptation to temperature fluctuations, we employed a quantitative mass spectrometry-based approach to probe key neuropeptides involving thermal adaptation in four lobster neural tissues at three temperatures: 4 {degrees}C (cold), 11 {degrees}C (control), and 18 {degrees}C (warm). Peptidomic profiling revealed a global reduction in peptide abundance during cold exposure, alongside coordinated, tissue-specific reconfigurations of the neuropeptidome between experimental groups. Cold exposure led to a significant downregulation of RFamide, leucokinin, and pyrokinin peptides in the commissural ganglia, whereas B-type allatostatin (AST-B), natalisin, and RYamide peptides were drastically elevated in the brain of warm-acclimated animals, with comparatively fewer detectable peptide abundance changes in the sinus gland and the stomatogastric ganglion. Collectively, our findings elucidate neuropeptide signaling pathways underlying thermal tolerance and adaptive resilience in Homarus americanus, offering insights into the survival mechanism and neurochemical basis of neural circuits in response to thermal acclimation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/710231v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@a3d24borg.highwire.dtl.DTLVardef@1434aaaorg.highwire.dtl.DTLVardef@db11cforg.highwire.dtl.DTLVardef@6e5995_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Persistent Adaptation through Dual-Timescale Regulation of Ion Channel Properties

Neurons are terminally differentiated cells that adapt to maintain stable function over years, despite encountering a wide range of environmental perturbations. Some adaptations are transient, fading once the perturbation ends. Others are persistent, continuing to influence a neurons responses to future challenges even after baseline conditions are restored. These persistent adaptations are especially intriguing because some remain undetectable under normal conditions--only becoming apparent upon re-exposure to a perturbation. Among the many mechanisms that may contribute to persistent adaptation, we investigate one based on the regulation of intrinsic currents. Using a computational model of activity-dependent homeostasis, we show that slow changes in channel density can encode the influence of past experience and shape future responses while rapid shifts in ion channel voltage-dependence provide immediate compensation during perturbations. Together, these dual processes tune a neurons intrinsic excitability, enabling persistent adaptation. SIGNIFICANCE STATEMENTSome neurons display a remarkable property: after adapting to environmental challenges, they return to baseline activity that looks unchanged, even though underlying modifications were made. These modifications may persist, shaping how the neuron responds to future perturbations. We term this phenomenon persistent adaptation. Although the underlying mechanisms of persistent adaptations may be diverse, here we demonstrate one possible route: homeostatic regulation of intrinsic excitability. Slow changes in channel density can store a trace of past perturbations, while rapid shifts in channel voltage-dependence can enable immediate recovery during re-exposure.

neuroscience↗

Temperature and pH-dependent Potassium Currents of Muscles of the Stomatogastric Nervous System of the Crab, Cancer borealis

Marine crustaceans, such as the crab Cancer borealis, experience large fluctuations in temperature and pH, yet their stomatogastric neuromuscular system must remain functional to support feeding. We examined 16 of the [~]40 pairs of stomach muscles and found that warming consistently hyperpolarized muscle fibers ([~]10 mV per 10 {degrees}C) and reduced excitatory junctional potentials and currents. Voltage-clamp analysis in the gastric muscle 5b (gm5b) revealed a temperature-activated conductance with a reversal potential near the potassium reversal potential, consistent with a potassium current, and insensitive to tetraethylammonium. Quantitative RT-PCR identified expression of two putative two-pore domain potassium (K2P) channels in these muscles. Muscle responses were also strongly influenced by extracellular pH. We observed an optimal operating window between pH 6.7-8.8; outside this range, responses diminished and abnormal activity, including spontaneous firing, appeared. Voltage-clamp recordings confirmed pH modulation of the same potassium conductance. Together, these results demonstrate that muscle excitability in Cancer borealis is shaped by temperature- and pH-sensitive currents, presumably carried by K2P channels. Functionally, these channels provide a plausible mechanism for stabilizing neuromuscular output despite environmental perturbations. As temperature increases, the pyloric and gastric rhythms accelerate, increasing synaptic drive to muscles. Activation of K2P channels counterbalances this input by reducing excitability, thereby preventing over-contraction and extending its dynamic range. This work highlights a muscle-intrinsic contribution to the well-known robustness of the stomatogastric system and identifies K2P channels as key players in adapting motor performance to changing environments. HighlightsO_LICancer borealis stomach muscles are sensitive to temperature and pH. C_LIO_LIWarming hyperpolarizes fibers and reduces synaptic response amplitude. C_LIO_LIKCNK1 and KCNK2, K2P channels mediate temperature- and pH-dependent conductances. C_LIO_LIMuscle K2Ps lower excitability, extending the functional range at high temperatures. C_LI In BriefThe crab Cancer borealis experiences large fluctuations in temperature and pH. We show that its stomach muscles hyperpolarize with warming and operate optimally within a narrow pH window. These effects are mediated by K2P channels (KCNK1, KCNK2), which reduce excitability and help maintain robust neuromuscular function under environmental change. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/680680v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@bec881org.highwire.dtl.DTLVardef@15d91a3org.highwire.dtl.DTLVardef@4777forg.highwire.dtl.DTLVardef@141444b_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Activity-Dependent Changes in Ion Channel Voltage-Dependence Influence the Activity Patterns Targeted by Neurons

Neurons can maintain stable activity profiles over their lifetimes despite ion channel turnover over minutes to weeks. Neuronal activity is also influenced by regulating the voltage-dependence of ion channels. How do these two forms of plasticity work together to maintain a stable activity profile? We augment a classical model of activity-dependent ion channel density regulation with a mechanism that adjusts channel voltage-dependence based on activity. These findings reveal that the timescale of these mechanisms shape the specific electrical activity patterns that achieve a target activity profile. Moreover, alterations in channel voltage-dependence can impact a neurons ability to recover from perturbations. These results highlight a potentially distinct role for activity-dependent regulation of channel voltage-dependence in maintaining stable neuronal activity profiles.

neuroscience↗

Rapid, interpretable, data-driven models of neural dynamics using Recurrent Mechanistic Models

Obtaining predictive models of a neural system is notoriously challenging. Detailed models suffer from excess model complexity and are difficult to fit efficiently. Simplified models must negotiate a tradeoff between tractability, predictive power and ease of interpretation. We present a new modelling paradigm for estimating predictive mechanistic-like models of neurons and small circuits that navigates these issues using methods from systems theory. The key insight is that membrane currents can be modelled using two scalable system components optimized for learning: linear state space models, and nonlinear artificial neural networks (ANNs). Combining these components, we construct two types of membrane currents: lumped currents, which are flexible, and data-driven conductance-based currents, which are interpretable. The resulting class of models -- which we call Recurrent Mechanistic Models (RMMs) -- can be trained in a matter of seconds to minutes on intracellular recordings during an electrophysiology experiment, representing a step change in performance over previous approaches. As a proof-of-principle, we use RMMs to learn the dynamics of two groups of neurons, and their synaptic connections, in the Stomatogastric Ganglion (STG), a well-known central pattern generator. We show that RMMs are efficiently trained using teacher forcing and multiple shooting. Due to their reliability, efficiency and interpretability, RMMs enable qualitatively new kinds of experiments using predictive models in closed-loop neurophysiology and online estimation of neural properties in living preparations. Significance StatementOur ability to understand the nervous system has been hindered by the difficulty of constructing good predictive models of neurons and circuits. This difficulty persists despite vast accumulated knowledge of how the basic components of the nervous system work, marking a gap in our ability to explain neural dynamics in terms of underlying mechanisms. This work describes a new data-driven modelling approach for neurons and small circuits that combines predictive power with mechanistic interpretation.

neuroscience↗

Circuit function is more robust to changes in synaptic than intrinsic conductances

Circuit function results from both intrinsic conductances of network neurons and the synaptic conductances that connect them. In models of neural circuits, different combinations of maximal conductances can give rise to similar activity. We compared the robustness of a neural circuit to changes in their intrinsic versus synaptic conductances. To address this, we performed a sensitivity analysis on a population of conductance-based models of the pyloric network from the crustacean stomatogastric ganglion (STG). The model network consists of three neurons with nine currents: a sodium current (Na), three potassium currents (Kd, KCa, A-type), two calcium currents (CaS and CaT), a hyperpolarization-activated current (H), a non-voltage-gated leak current (leak), and a neuromodulatory current (MI). The model cells are connected by seven synapses of two types, glutamatergic and cholinergic. We produced one hundred models of the pyloric network that displayed similar activities with values of maximal conductances distributed over wide ranges. We evaluated the robustness of each model to changes in their maximal conductances. We found that individual models have different sensitivities to changes in their maximal conductances, both in their intrinsic and synaptic conductances. As expected the models become less robust as the extent of the changes increase. Despite quantitative differences in their robustness, we found that in all cases, the model networks are more sensitive to the perturbation of their intrinsic conductances than their synaptic conductances.

neuroscience↗

Sulfonylurea receptor coupled conductances alter the performance of two central pattern generating circuits in Cancer borealis

Neuronal activity and energy supply must maintain a fine balance for neuronal fitness. Various channels of communication between the two could impact network output in different ways. Sulfonylurea receptors (SURs) are a modification of ATP-binding cassette proteins (ABCs) that confer ATP-dependent gating on their associated ion channels. They are widely expressed and link metabolic states directly to neuronal activity. The role they play varies in different circuits, both enabling bursting and inhibiting activity in pathological conditions. The crab, Cancer borealis, has central patterns generators (CPGs) that fire in rhythmic bursts nearly constantly and it is unknown how energy availability influences these networks. The pyloric network of the stomatogastric ganglion (STG) and cardiac ganglion (GC) control rhythmic contractions of the foregut and heart respectively. Pharmacological manipulation of SURs results in opposite effects in the two CPGs. Neuronal firing completely stops in the STG when SUR-associated channels are open, and firing increases when the channels are closed. This results from a decrease in the excitability of pyloric dilator (PD) neurons, which are a part of the pacemaker kernel. The neurons of the CG, paradoxically, increase firing within bursts when SUR-associated channels are opened, and bursting slows when SUR-associated channels are closed. The channel permeability and sensitivities analyses present novel SUR-conductance biophysics, which nevertheless change activity in ways reminiscent of the predominantly studied mammalian receptor/channels. We suggest that SUR-associated conductances allow different neurons to respond to energy states in different ways through a common mechanism.

neuroscience↗

Ih Block Reveals Separation of Timescales in Pyloric Rhythm Response to Temperature Changes in Cancer borealis

Motor systems operate over a range of frequencies and relative timing (phase). We studied the contribution of the hyperpolarization-activated inward current (Ih) to frequency and phase in the pyloric rhythm of the stomatogastric ganglion (STG) of the crab, Cancer borealis as temperature was altered from 11{degrees}C to 21{degrees}C. Under control conditions, the frequency of the rhythm increased monotonically with temperature, while the phases of the pyloric dilator (PD), lateral pyloric (LP), and pyloric (PY) neurons remained constant. When we blocked Ih with cesium (Cs+) PD offset, LP onset, and LP offset were all phase advanced in Cs+ at 11{degrees}C, and the latter two further advanced as temperature increased. In Cs+ the steady state increase in pyloric frequency with temperature diminished and the Q10 of the pyloric frequency dropped from [~]1.75 to [~]1.35. Unexpectedly in Cs+, the frequency displayed non-monotonic dynamics during temperature transitions; the frequency initially dropped as temperature increased, then rose once temperature stabilized, creating a characteristic "jag". Interestingly, these jags were still present during temperature transitions in Cs+ when the pacemaker was isolated by picrotoxin, although the temperature-induced change in frequency recovered to control levels. Overall, these data suggest that Ih plays an important role in the ability of this circuit to produce smooth transitory responses and persistent frequency increases by different mechanisms during temperature fluctuations.

neuroscience↗

Sodium channel slow inactivation normalizes firing in axons with uneven conductance distributions

The Na+ channels that are important for action potentials show rapid inactivation, a state in which they do not conduct, although the membrane potential remains depolarized1,2. Rapid inactivation is a determinant of millisecond scale phenomena, such as spike shape and refractory period. Na+ channels also inactivate orders of magnitude more slowly, and therefore have impacts on excitability over much longer time scales than those of a single spike or a single inter-spike interval3-9. Here, we focus on the contribution of slow inactivation to the resilience of axonal excitability10,11 when ion channels are unevenly distributed across the axonal membrane. We study models in which the voltage-gated Na+ and K+ channels are unevenly distributed along axons with different variances, capturing the heterogeneity that biological axons display12. In the absence of slow inactivation many conductance distributions result in spontaneous tonic activity. Faithful axonal propagation is achieved with the introduction of Na+ channel slow inactivation. This "normalization" effect depends on relations between the kinetics of slow inactivation and the firing frequency. Consequently, neurons with characteristically different firing frequencies will need to implement different sets of channel properties to achieve resilience. The results of this study demonstrate the importance of the intrinsic biophysical properties of ion channels in normalizing axonal function. HighlightsO_LIVariation in ion channel density in axons may compromise axonal spike propagation. C_LIO_LISlow inactivation of Na+ channels modulates their availability. C_LIO_LINa+ channel slow inactivation increases the reliability of spike propagation. C_LIO_LINormalization by slow inactivation can compensate for uneven channel distributions. C_LI

neuroscience↗

Neuronal Morphology Enhances Robustness to Perturbations of Channel Densities

Biological neurons show significant cell-to-cell variability but have the striking ability to maintain their key firing properties in the face of unpredictable perturbations and stochastic noise. Using a population of multi-compartment models consisting of soma, neurites, and axon for the lateral pyloric (LP) neuron in the crab stomatogastric ganglion, we explored how rebound bursting is preserved when the 14 channel conductances in each model are all randomly varied. The soma-axon coupling is critical for the ability of the axon to spike during bursts and consequently determines the set of successful solutions. When the coupling deviates from a biologically realistic range, the neuronal tolerance of conductance variations is significantly lessened. Thus, the gross morphological features of these neurons enhance their robustness to perturbations of channel densities and expands the space of individual variability that can maintain a desired output pattern.

neuroscience↗

Localization of chemical synapses and modulatory release sites in the cardiac ganglion of the crab, Cancer borealis

The crustacean cardiac ganglion (CG) comprises nine neurons that provide rhythmic drive to the heart. The CG is the direct target of multiple modulators. Synapsin-like immunoreactivity was found clustered around the somata of the large cells (LC) and in a neuropil at the anterior branch of the CG trunk. This implicates the soma as a key site of synaptic integration, an unusual configuration in invertebrates. Proctolin is an excitatory neuromodulator of the CG and proctolin-like immunoreactivity exhibited partial overlap with putative chemical synapses near the LCs and at the neuropil. A proctolin-like projection was also found in a pair of excitatory nerves entering the CG. GABA-like immunoreactivity was nearly completely colocalized with chemical synapses near the LCs but absent at the anterior branch neuropil. GABA-like projections were found in a pair of inhibitory nerves entering the CG. Cancer borealis Allatostatin B1 (CbAST-B1), red pigment concentrating hormone (RPCH) and FLMRFamide-like immunoreactivity each had a unique pattern of staining and co-localization with putative chemical synapses. These results provide morphological evidence that synaptic input is integrated at LC somata in the CG. Our findings provide a topographical organization for some of the multiple inhibitory and excitatory modulators that alter the rhythmic output of this semi-autonomous motor circuit.

neuroscience↗

RECIPROCALLY INHIBITORY CIRCUITS OPERATING WITH DISTINCT MECHANISMS ARE DIFFERENTLY ROBUST TO PERTURBATION AND MODULATION

What features are important for circuit robustness? Reciprocal inhibition is a building block in many circuits. We used dynamic clamp to create reciprocally inhibitory circuits from pharmacologically isolated neurons of the crab stomatogastric ganglion by injecting artificial synaptic (ISyn) and hyperpolarization-activated inward (IH) currents. There are two mechanisms of antiphase oscillations in these circuits: "escape" and "release". In release, the active neuron primarily controls the off/on transitions. In escape, the inhibited neuron controls the transitions. We characterized the robustness of escape and release circuits to alterations in circuit parameters, temperature, and neuromodulation. We found that escape circuits rely on tight correlations between synaptic and H conductances to generate bursting but are resilient to temperature increase. Release circuits are robust to variations in synaptic and H conductances but fragile to temperature increase. The modulatory current (IMI) restores oscillations in release circuits but has little effect in escape circuits. Thus, the same perturbation can have dramatically different effects depending on the circuits mechanism of operation that may not be observable from basal circuit activity.

neuroscience↗

Mapping circuit dynamics during function and dysfunction

Neural circuits can generate many spike patterns, but only some are functional. The study of how circuits generate and maintain functional dynamics is hindered by a poverty of description of circuit dynamics across functional and dysfunctional states. For example, although the regular oscillation of a central pattern generator is well characterized by its frequency and the phase relationships between its neurons, these metrics are ineffective descriptors of the irregular and aperiodic dynamics that circuits can generate under perturbation or in disease states. By recording the circuit dynamics of the well-studied pyloric circuit in C. borealis, we used statistical features of spike times from neurons in the circuit to visualize the spike patterns generated by this circuit under a variety of conditions. This unsupervised approach captures both the variability of functional rhythms and the diversity of atypical dynamics in a single map. Clusters in the map identify qualitatively different spike patterns hinting at different dynamical states in the circuit. State probability and the statistics of the transitions between states varied with environmental perturbations, removal of descending neuromodulation, and the addition of exogenous neuromodulators. This analysis reveals strong mechanistically interpretable links between complex changes in the collective behavior of a neural circuit and specific experimental manipulations, and can constrain hypotheses of how circuits generate functional dynamics despite variability in circuit architecture and environmental perturbations.

neuroscience↗

A model of rapid homeostatic plasticity accounts for hidden, long-lasting changes in a neuronal circuit after exposure to high potassium.

Neural circuits must both function reliably and flexibly adapt to changes in their environment. We studied how both biological neurons and computational models respond to high potassium concentrations. Pyloric neurons of the crab stomatogastric ganglion (STG) initially become quiescent, then recover spiking activity in high potassium saline. The neurons retain this adaptation and recover more rapidly in subsequent high potassium applications, even after hours in control saline. We constructed a novel activity-dependent computational model that qualitatively captures these results. In this model, regulation of conductances is gated on and off depending on how far the neuron is from its target activity. This allows the model neuron to retain a trace of past perturbations even after it returns to its target activity in control conditions. Thus, perturbation, followed by recovery of normal activity, can hide cryptic changes in neuronal properties that are only revealed by subsequent perturbations.

neuroscience↗

Interactions between Diameter, Myelination and the Na/K pump Affect Axonal Resilience to High Frequency Spiking

Axons reliably conduct action potentials between neurons and/or other targets. Axons have widely variable diameters and can be myelinated or unmyelinated. Although the effect of these factors on propagation speed is well studied, how they constrain axonal resilience to high frequency spiking is incompletely understood. Maximal firing frequencies range from ~ 1 Hz to > 300 Hz across neurons, but the process by which Na/K pumps counteract Na+ influx is slow, and it is unclear the extent to which slow Na+ removal is compatible with high frequency spiking. Modeling the process of Na+ removal shows that large diameter axons are more resilient to high frequency spikes than small diameter axons, because of their slow Na+ accumulation. In myelinated axons, the myelinated compartments between nodes of Ranvier act as a reservoir to slow Na+ accumulation and increase the reliability of axonal propagation. We now find that slowing the activation of K+ current can increase the Na+ influx rate, and the effect of minimizing the overlap between Na+- and K+-currents on spike propagation resilience depends on complex interactions among diameter, myelination and the Na/K pump density. Our results suggest that, in neurons with different channel gating kinetic parameters, different strategies may be required to improve the reliability of axonal propagation. Significance StatementThe reliability of spike propagation in axons is determined by complex interactions among ionic currents, ion pumps and morphological properties. We use compartment-based modeling to reveal that interactions of diameter, myelination and the Na/K pump determine the reliability of high frequency spike propagation. By acting as a reservoir of nodal Na+ influx, myelinated compartments efficiently increase propagation reliability. Although spike broadening was thought to oppose fast spiking, its effect on spike propagation is complicated, depending on the balance of Na+ channel inactivation gate recovery, Na+ influx and axial charge. Our findings suggest that slow Na+ removal influences axonal resilience to high frequency spike propagation, and that different strategies may be required to overcome this constraint in different neurons.

neuroscience↗

Degenerate circuits use distinct mechanisms to respond similarly to the same perturbation

There is considerable flexibility embedded within neural circuits. For example, separate modulatory inputs can differently configure the same underlying circuit but these different configurations generate comparable, or degenerate, activity patterns. However, little is known about whether these mechanistically different circuits in turn exhibit degenerate responses to the same inputs. We examined this issue using the crab (Cancer borealis) stomatogastric nervous system, in which stimulating the modulatory projection neuron MCN1 and bath applying the neuropeptide CabPK II elicit similar gastric mill (chewing) rhythms in the stomatogastric ganglion, despite differentially configuring the same neural circuit. We showed previously that bath applying the peptide hormone CCAP or stimulating the muscle stretch-sensitive sensory neuron GPR during the MCN1-elicited gastric mill rhythm selectively prolongs the protraction or retraction phase, respectively. Here, we found that these two influences on the CabPK-rhythm elicited some unique and unexpected consequences compared to their actions on the MCN1-rhythm. For example, in contrast to its effect on the MCN1-rhythm, CCAP selectively decreased the CabPK-rhythm retraction phase and thus increased the rhythm speed, whereas the CabPK-rhythm response to stimulating GPR during the retraction phase was similar its effect on the MCN1-rhythm (i.e. prolonging retraction). Interestingly, despite the comparable GPR actions on these degenerate rhythms, the underlying synaptic mechanism was distinct. Thus, degenerate circuits do not necessarily exhibit degenerate responses to the same influence, but when they do, it can occur via different underlying mechanisms. Significance StatementCircuits generating seemingly identical behaviors are often thought to arise from identical circuit states, as that is the most parsimonious explanation. Here we take advantage of an alternate scenario wherein a well-defined circuit with known connectivity generates similar activity patterns using distinct circuit states, via known mechanisms. The same peptide hormone modulation of these distinct circuit states produced divergent activity patterns, whereas the same sensory feedback altered these circuit outputs similarly but via different synaptic pathways. The latter observation limits the insights available from comparable studies in systems lacking detailed access to the underlying circuit.

neuroscience↗