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Eve Marder

Publications and source records attributed to Eve Marder.

At least 37 records · Page 2Linked to original sources
PubMed2005

Development of central pattern generating circuits.

The networks that generate rhythmic motor patterns in invertebrates and vertebrates are ideal for studying the mechanisms by which functional circuits are formed during development. Rhythmic motor patterns and movements are seen embryonically, before they are needed for behavior; recent work suggests that activity in immature spinal cord networks is important for circuit formation and transmitter specification. Despite significant advances in describing the patterns of transcription factor expression in both invertebrate nervous systems and vertebrate spinal cord, a real understanding of how central pattern generators develop is hindered by our lack of knowledge of the organization of these circuits in adults.

Animals↗
PubMed2005

Profiling of neuropeptides released at the stomatogastric ganglion of the crab, Cancer borealis with mass spectrometry.

Studies of release under physiological conditions provide more direct data about the identity of neuromodulatory signaling molecules than studies of tissue localization that cannot distinguish between processing precursors and biologically active neuropeptides. We have identified neuropeptides released by electrical stimulation of nerves that contain the axons of the modulatory projection neurons to the stomatogastric ganglion of the crab, Cancer borealis. Preparations were bathed in saline containing a cocktail of peptidase inhibitors to minimize peptide degradation. Both electrical stimulation of projection nerves and depolarization with high K+ saline were used to evoke release. Releasates were desalted and then identified by mass using MALDI-TOF (matrix-assisted laser desorption/ionization-time-of-flight) mass spectrometry. Both previously known and novel peptides were detected. Subsequent to electrical stimulation proctolin, Cancer borealis tachykinin-related peptide (CabTRP), FVNSRYa, carcinustatin-8, allatostatin-3 (AST-3), red pigment concentrating hormone, NRNFLRFa, AST-5, SGFYANRYa, TNRNFLRFa, AST-9, orcomyotropin-related peptide, corazonin, Ala13-orcokinin, and Ser9-Val13-orcokinin were detected. Some of these were also detected after high K+ depolarization. Release was calcium dependent. In summary, we have shown release of the neuropeptides thought to play an important neuromodulatory role in the stomatogastric ganglion, as well as numerous other candidate neuromodulators that remain to be identified.

Animals↗
PubMed2004

Similar network activity from disparate circuit parameters.

It is often assumed that cellular and synaptic properties need to be regulated to specific values to allow a neuronal network to function properly. To determine how tightly neuronal properties and synaptic strengths need to be tuned to produce a given network output, we simulated more than 20 million versions of a three-cell model of the pyloric network of the crustacean stomatogastric ganglion using different combinations of synapse strengths and neuron properties. We found that virtually indistinguishable network activity can arise from widely disparate sets of underlying mechanisms, suggesting that there could be considerable animal-to-animal variability in many of the parameters that control network activity, and that many different combinations of synaptic strengths and intrinsic membrane properties can be consistent with appropriate network performance.

Action Potentials↗
PubMed2004

Plasticity in single neuron and circuit computations.

Plasticity in neural circuits can result from alterations in synaptic strength or connectivity, as well as from changes in the excitability of the neurons themselves. To better understand the role of plasticity in the brain, we need to establish how brain circuits work and the kinds of computations that different circuit structures achieve. By linking theoretical and experimental studies, we are beginning to reveal the consequences of plasticity mechanisms for network dynamics, in both simple invertebrate circuits and the complex circuits of mammalian cerebral cortex.

Animals↗
PubMed2004

Octopamine modulates the axons of modulatory projection neurons.

Octopamine increases the cycle frequency of the pyloric rhythm in the crab Cancer borealis by acting at multiple sites within the stomatogastric nervous system. The junction between the stomatogastric nerve (stn) and the superior esophageal nerve (son) shows synaptic structures. When applied only to the stn-son junction, octopamine induced action potentials in the axons of the modulatory commissural neuron 5 (MCN5) that project from the commissural ganglia to the stomatogastric ganglion (STG). The activation of the MCN5 neurons was correlated with an increase in the pyloric rhythm frequency. Additionally, octopamine had direct effects on the STG, including the activation of the pyloric dilator and pyloric neurons, an increase in the pyloric frequency, and a change in the phase relationships of the pyloric neurons. Thus, the same modulator can influence the pyloric rhythm by acting at multiple sites, including the axons of identified modulatory neurons that project to the STG. These data demonstrate that axonal propagation may be influenced locally by neuromodulators acting on axonal receptors, therefore altering the conduction of information from different command and integrating centers.

Action Potentials↗
PubMed2004

Nitric oxide inhibits the rate and strength of cardiac contractions in the lobster Homarus americanus by acting on the cardiac ganglion.

The lobster heart is synaptically driven by the cardiac ganglion, a spontaneously bursting neural network residing within the cardiac lumen. Here, we present evidence that nitric oxide (NO) plays an inhibitory role in lobster cardiac physiology. (1) NO decreases heartbeat frequency and amplitude. Decreased frequency is a direct consequence of a decreased ganglionic burst rate. Decreased amplitude is an indirect consequence of decreased burst frequency, attributable to the highly facilitating nature of the synapses between cardiac ganglion neurons and muscle fibers (although, during prolonged exposure to NO, amplitude recovers to the original level by a frequency-independent adaptation mechanism). NO does not alter burst duration, spikes per burst, heart muscle contractility, or amplitudes of synaptic potentials evoked by stimulating postganglionic motor nerves. Thus, NO acts on the ganglion, but not on heart muscle. (2) Two observations suggest that NO is produced within the lobster heart. First, immunoblot analysis shows that nitric oxide synthase (NOS) is strongly expressed in heart muscle relative to other muscles. Second, L-nitroarginine (L-NA), an NOS inhibitor, increases the rate of the heartbeat (opposite to the effects of NO). In contrast, the isolated ganglion is insensitive to L-NA, suggesting that heart muscle (but not the ganglion) produces endogenous NO. Basal heart rate varies from animal to animal, and L-NA has the greatest effect on the slowest hearts, presumably because these hearts are producing the most NO. Thus, because the musculature is a site of NOS expression, whereas the ganglion is the only intracardiac target of NO, we hypothesize that NO serves as an inhibitory retrograde transmitter.

Adaptation, Physiological↗
PubMed2004

Actions of a histaminergic/peptidergic projection neuron on rhythmic motor patterns in the stomatogastric nervous system of the crab Cancer borealis.

Histamine is a neurotransmitter with actions throughout the nervous system of vertebrates and invertebrates. Nevertheless, the actions of only a few identified histamine-containing neurons have been characterized. Here, we present the actions of a histaminergic projection neuron on the rhythmically active pyloric and gastric mill circuits within the stomatogastric ganglion (STG) of the crab Cancer borealis. An antiserum generated against histamine labeled profiles throughout the C. borealis stomatogastric nervous system. Labeling occurred in several somata and neuropil within the paired commissural ganglia as well as in neuropil within the STG and at the junction of the superior oesophageal and stomatogastric nerves. The source of all histamine-like immunolabeling in the STG neuropil was one pair of neuronal somata, the previously identified inferior ventricular (IV) neurons, located in the supraoesophageal ganglion. These neurons also exhibited FLRFamide-like immunoreactivity. Activation of the IV neurons in the crab inhibited some pyloric and gastric mill neurons and, with inputs from the commissural ganglia eliminated, terminated both rhythms. Focal application of histamine had comparable effects. The actions of both applied histamine and IV neuron stimulation were blocked, reversibly, by the histamine type-2 receptor antagonist cimetidine. With the commissural ganglia connected to the STG, IV neuron stimulation elicited a longer-latency activation of commissural projection neurons which in turn modified the pyloric rhythm and activated the gastric mill rhythm. These results support the hypothesis that the histaminergic/peptidergic IV neurons are projection neurons with direct and indirect actions on the STG circuits of the crab C. borealis.

Action Potentials↗
PubMed2004

The dynamic clamp comes of age.

The dynamic clamp uses computer simulation to introduce artificial membrane or synaptic conductances into biological neurons and to create hybrid circuits of real and model neurons. In the ten years since it was first developed, the dynamic clamp has become a widely used tool for the study of neural systems at the cellular and circuit levels. This review describes recent state-of-the-art implementations of the dynamic clamp and summarizes insights gained through its use, ranging from the role of voltage-dependent conductances in shaping neuronal activity to the effects of synaptic dynamics on network behavior and the impact of in vivo-like input on neuronal information processing.

Animals↗
PubMed2004

Welcome theory.

Explore the source record for details and available documents.

Models, Theoretical↗
PubMed2003

Differential and history-dependent modulation of a stretch receptor in the stomatogastric system of the crab, Cancer borealis.

Neuromodulators can modify the magnitude and kinetics of the response of a sensory neuron to a stimulus. Six neuroactive substances modified the activity of the gastropyloric receptor 2 (GPR2) neuron of the stomatogastric nervous system (STNS) of the crab Cancer borealis during muscle stretch. Stretches were applied to the gastric mill 9 (gm9) and the cardio-pyloric valve 3a (cpv3a) muscles. SDRNFLRFamide and dopamine had excitatory effects on GPR2. Serotonin, GABA, and the peptide allatostatin-3 (AST) decreased GPR2 firing during stretch. Moreover, SDRNFLRFamide and TNRNFLRFamide increased the unstimulated spontaneous firing rate, whereas AST and GABA decreased it. The actions of AST and GABA were amplitude- and history-dependent. In fully recovered preparations, AST and GABA decreased the response to small-amplitude stretches proportionally more than to those evoked by large-amplitude stretches. For large-amplitude stretches, the effects of AST and GABA were more pronounced as the number of recent stretches increased. The modulators that affected the stretch-induced GPR2 firing rate were also tested when the neuron was operating in a bursting mode of activity. Application of SDRNFLRFamide increased the bursting frequency transiently, whereas high concentrations of serotonin, AST, and GABA abolished bursting altogether. Together these data demonstrate that the effects of neuromodulators depend on the previous activity and current state of the sensory neuron.

Action Potentials↗
PubMed2003

Alternative to hand-tuning conductance-based models: construction and analysis of databases of model neurons.

Conventionally, the parameters of neuronal models are hand-tuned using trial-and-error searches to produce a desired behavior. Here, we present an alternative approach. We have generated a database of about 1.7 million single-compartment model neurons by independently varying 8 maximal membrane conductances based on measurements from lobster stomatogastric neurons. We classified the spontaneous electrical activity of each model neuron and its responsiveness to inputs during runtime with an adaptive algorithm and saved a reduced version of each neuron's activity pattern. Our analysis of the distribution of different activity types (silent, spiking, bursting, irregular) in the 8-dimensional conductance space indicates that the coarse grid of conductance values we chose is sufficient to capture the salient features of the distribution. The database can be searched for different combinations of neuron properties such as activity type, spike or burst frequency, resting potential, frequency-current relation, and phase-response curve. We demonstrate how the database can be screened for models that reproduce the behavior of a specific biological neuron and show that the contents of the database can give insight into the way a neuron's membrane conductances determine its activity pattern and response properties. Similar databases can be constructed to explore parameter spaces in multicompartmental models or small networks, or to examine the effects of changes in the voltage dependence of currents. In all cases, database searches can provide insight into how neuronal and network properties depend on the values of the parameters in the models.

Algorithms↗
PubMed2003

Dopamine and histamine in the developing stomatogastric system of the lobster Homarus americanus.

Dopamine and histamine are neuromodulators found in the adult stomatogastric nervous system (STNS) of several crustacean species. We used antibodies against tyrosine hydroxylase (TH) and histamine to map the distribution and developmental acquisition of the dopamine and histamine neurons in the STNS of the lobster, Homarus americanus. Embryos, larvae, juvenile and adult animals were studied. TH labeling was present in the STNS as early as E80-85 (80-85% of embryonic development). A subset of preparations in embryos, larvae, juveniles, and adults contained 1-5 labeled somata in the stomatogastric ganglion. Histamine staining appeared in the STNS as early as E50. The distribution of both TH and histamine staining remained relatively constant through development. Electrophysiological recordings demonstrated that receptors for both amines are present in the embryo. Bath application of dopamine increased the frequency of the pyloric rhythm in embryos, and evidence for dopaminergic activation of peripherally initiated spiking in motor axons was seen. In embryos and adults, histamine inhibited the motor patterns produced by the stomatogastric ganglion (STG). These data suggest that the dopaminergic and histaminergic systems in H. americanus appear relatively early in development and that the effects of each are largely maintained through development.

Animals↗
PubMed2003

Axonal dopamine receptors activate peripheral spike initiation in a stomatogastric motor neuron.

We studied the effects of dopamine on the stomatogastric ganglion (STG) of the lobster, Homarus americanus. The two pyloric dilator (PD) neurons are active in the pyloric rhythm, have somata in the STG, and send axons many centimeters to innervate muscles of the stomach. Dopamine application to the stomatogastric nervous system when the PD neurons were rhythmically active evoked additional action potentials during the PD neuron interburst intervals. These action potentials were peripherally generated at a region between the STG and the first bilateral branch, approximately 1 cm away from the STG, and traveled antidromically to the neuropil and orthodromically to the pyloric dilator muscles. Focal applications of dopamine to the nerves showed that spikes could be initiated in almost the entire peripheral axon of the PD neurons. Dopamine also evoked spikes in isolated peripheral axons. The concentration threshold for peripheral spike initiation was at or below 10-9 m dopamine. Thus, the peripheral axon can play an important role in shaping the output signaling to the muscles by the motor neuron.

Action Potentials↗
PubMed2003

Episodic bouts of activity accompany recovery of rhythmic output by a neuromodulator- and activity-deprived adult neural network.

The pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis, slows or stops when descending modulatory inputs are acutely removed. However, the rhythm spontaneously resumes after one or more days in the absence of neuromodulatory input. We recorded continuously for days to characterize quantitatively this recovery process. Activity bouts lasting 40-900 s began several hours after removal of neuromodulatory input and were followed by stable rhythm recovery after 1-4 days. Bout duration was not related to the intervals (0.3-800 min) between bouts. During an individual bout, the frequency rapidly increased and then decreased more slowly. Photoablation of back-filled neuromodulatory terminals in the stomatogastric ganglion (STG) neuropil had no effect on activity bouts or recovery, suggesting that these processes are intrinsic to the STG neuronal network. After removal of neuromodulatory input, the phase relationships of the components of the triphasic pyloric rhythm were altered, and then over time the phase relationships moved toward their control values. Although at low pyloric rhythm frequency the phase relationships among pyloric network neurons depended on frequency, the changes in frequency during recovery did not completely account for the change in phase seen after rhythm recovery. We suggest that activity bouts represent underlying mechanisms controlling the restructuring of the pyloric network to allow resumption of an appropriate output after removal of neuromodulatory input.

Action Potentials↗
PubMed2003

Serotonin in the developing stomatogastric system of the lobster, Homarus americanus.

We studied the development of the serotonergic modulation of the stomatogastric nervous system of the lobster, Homarus americanus. Although the stomatogastric ganglion (STG) is present early in embryonic development, serotonin immunoreactivity is not visible in the STG until the second larval stage. However, incubation of the STG with exogenous serotonin showed that a serotonin transporter is present in embryonic and early larval stages. Serotonin uptake was blocked by paroxetine and 0% Na(+) saline. The presence of a serotonin transporter in the embryonic STG suggests that hormonally liberated serotonin could be taken up by the STG, and potentially released as a "borrowed transmitter". Consistent with a potential hormonal role, serotonin is found in the pericardial organs, a major neurosecretory structure, by midembryonic development. The rhythmic motor patterns produced by embryonic and larval STGs were decreased in frequency by serotonin. Lateral Pyloric (LP) neuron-evoked excitatory junctional potentials (EJPs) in the embryos and the first larval stage (LI) were larger, slower, and more variable than those in the adult. The amplitude of adult LP neuron-evoked EJPs was increased more than twofold in serotonin, but in embryos and LI preparations this effect was negligible. In embryos and LI preparations, serotonin increased the occurrence of muscle fiber action potentials and altered the EJP wave-form. These data demonstrate that serotonin receptors are present in the stomatogastric nervous system early in development, and suggest that the role of serotonin changes from modulation of muscle fiber excitability early in development to enhancement of neurally evoked EJPs in the adult.

Age Factors↗
PubMed2003

The functional consequences of changes in the strength and duration of synaptic inputs to oscillatory neurons.

We studied the effect of synaptic inputs of different amplitude and duration on neural oscillators by simulating synaptic conductance pulses in a bursting conductance-based pacemaker model and by injecting artificial synaptic conductance pulses into pyloric pacemaker neurons of the lobster stomatogastric ganglion using the dynamic clamp. In the model and the biological neuron, the change in burst period caused by inhibitory and excitatory inputs of increasing strength saturated, such that synaptic inputs above a certain strength all had the same effect on the firing pattern of the oscillatory neuron. In contrast, increasing the duration of the synaptic conductance pulses always led to changes in the burst period, indicating that neural oscillators are sensitive to changes in the duration of synaptic input but are not sensitive to changes in the strength of synaptic inputs above a certain conductance. This saturation of the response to progressively stronger synaptic inputs occurs not only in bursting neurons but also in tonically spiking neurons. We identified inward currents at hyperpolarized potentials as the cause of the saturation in the model neuron. Our findings imply that activity-dependent or modulator-induced changes in synaptic strength are not necessarily accompanied by changes in the functional impact of a synapse on the timing of postsynaptic spikes or bursts.

Action Potentials↗
PubMed2003

Current compensation in neuronal homeostasis.

How do neurons maintain stable intrinsic properties over long periods of time as the channels that govern excitability turn over in the membrane? In this issue of Neuron, MacLean et al. argue that homeostatic regulation of intrinsic activity can occur by an activity-independent mechanism.

Action Potentials↗