Search PubMed⌕ Search

Biomedical subjects

E Marder

Publications and source records attributed to E Marder.

At least 55 records · Page 3Linked to original sources
PubMed1997

Temporal dynamics of graded synaptic transmission in the lobster stomatogastric ganglion.

Synaptic transmission between neurons in the stomatogastric ganglion of the lobster Panulirus interruptus is a graded function of membrane potential, with a threshold for transmitter release in the range of -50 to -60 mV. We studied the dynamics of graded transmission between the lateral pyloric (LP) neuron and the pyloric dilator (PD) neurons after blocking action potential-mediated transmission with 0.1 microM tetrodotoxin. We compared the graded IPSPs (gIPSPs) from LP to PD neurons evoked by square pulse presynaptic depolarizations with those potentials evoked by realistic presynaptic waveforms of variable frequency, amplitude, and duty cycle. The gIPSP shows frequency-dependent synaptic depression. The recovery from depression is slow, and as a result, the gIPSP is depressed at normal pyloric network frequencies. Changes in the duration of the presynaptic depolarization produce nonintuitive changes in the amplitude and time course of the postsynaptic responses, which are again frequency-dependent. Taken together, these data demonstrate that the measurements of synaptic efficacy that are used to understand neural network function are best made using presynaptic waveforms and patterns of activity that mimic those in the functional network.

Animals↗
PubMed1997

Modulation of oscillator interactions in the crab stomatogastric ganglion by crustacean cardioactive peptide.

The modulation of the pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis, by crustacean cardioactive peptide (CCAP) is described. CCAP activated pyloric rhythms in most silent preparations, and altered the phase relationships of pyloric motor neuron firing in all preparations. In CCAP, the pyloric rhythms were characterized by long lateral pyloric (LP) neuron bursts of action potentials. The threshold for CCAP action was approximately 10(-10) M, with increasing effects at higher CCAP concentrations. The changes in motor pattern evoked by CCAP produced significant changes in LP-innervated muscle movement. These movements were additionally potentiated by CCAP applications to isolated nerve-muscle preparations. Thus, enhanced motor neuron firing and increase of the gain of the neuromuscular junctions are likely to operate coordinately in response to hormonally released CCAP. High CCAP concentrations sometimes resulted in modification of the normal 1:1 alternation between the pyloric dilator (PD) and LP neurons to patterns of 2:1, 3:1, or 4:1 alternation. CCAP seems to activate slow intrinsic oscillations in the LP neuron, as well as enhance faster oscillations in the pacemaker group of PD/anterior burster (AB) neurons. Simulations of fast and slow oscillators with reciprocal inhibitory coupling suggest mechanisms that could account for the mode switch from 1:1 alternation to multiple PD bursts alternating with one LP neuron burst.

Action Potentials↗
PubMed1997

Organization of the stomatogastric neuropil of the crab, Cancer borealis, as revealed by modulator immunocytochemistry.

We used antibodies to a number of neuromodulatory substances, including serotonin, FLRF amide, red pigment-concentrating hormone, substance P, proctolin and cholecystokinin, to investigate the distribution of molecules similar to these substances in the stomatogastric ganglion of the crab, Cancer borealis. No immunoreactivity was seen in the region of the cell bodies that surrounds the neuropil and little was found in the core of the neuropil (where the primary neurites of the intrinsic neurons occupy most of the space). Instead, modulator immunolabel was densely packed in the more peripheral portion of the neuropil that surrounded the core. Within this peripheral neuropil, profiles appeared quite uniformly distributed. Double-labeling showed that there were limited differences in distribution between the labels examined in our study. The only immunolabeled structures that showed a distinct differential distribution within the stomatogastric neuropil were a population of >/=10 microm varicosities that arose from a pair of input fibers that we termed the large varicosity fibers. These varicosities were immunolabelled by antisera for three different peptides. Taken collectively, these data shows that there is a stereotyped distribution of modulator immunoreactivity within the crab stomatogastric neuropil. However, this segregation is more rudimentary than that reported for the intrinsic stomatogastric neurons.

Animals↗
PubMed1997

D-glucose-sensitive neurosecretory cells of the crab Cancer borealis and negative feedback regulation of blood glucose level.

We studied the effects of glucose on cultured X-organ neurons of the crab Cancer borealis using single-electrode current- and voltage-clamp techniques. A subpopulation of the cells responded to D-glucose with a hyperpolarization. These cells, but not glucose-insensitive cells, showed immunoreactivity to crustacean hyperglycemic hormone (CHH), the hormone responsible for the elevation of blood glucose levels in crustaceans. Glucose-sensitive cells were also inhibited by serotonin and gamma-aminobutyric acid but were not affected by dopamine and Leu-enkephalin. The response was specific for D-glucose, with an EC50 of 0.25 mmoll-1. No response was seen to L-glucose, sucrose, galactose, mannose or fructose. The glucose response persisted in the absence of extracellular Na+ and in low-Ca2+/Mn2+ saline. In voltage-clamp experiments, D-glucose evoked a small current with a reversal potential close to that of voltage-dependent K+ currents. We conclude that D-glucose activates a K+ current in CHH-immunoreactive cells that, in normal saline, induces a hyperpolarization. We propose that this enables glucose to regulate directly the release of CHH into the hemolymph, thus constituting a negative feedback mechanism regulating hemolymph glucose concentration.

Animals↗
PubMed1996

Memory from the dynamics of intrinsic membrane currents.

Almost all theoretical and experimental studies of the mechanisms underlying learning and memory focus on synaptic efficacy and make the implicit assumption that changes in synaptic efficacy are both necessary and sufficient to account for learning and memory. However, network dynamics depends on the complex interaction between intrinsic membrane properties and synaptic strengths and time courses. Furthermore, neuronal activity itself modifies not only synaptic efficacy but also the intrinsic membrane properties of neurons. This paper presents examples demonstrating that neurons with complex temporal dynamics can provide short-term "memory" mechanisms that rely solely on intrinsic neuronal properties. Additionally, we discuss the potential role that activity may play in long-term modification of intrinsic neuronal properties. While not replacing synaptic plasticity as a powerful learning mechanism, these examples suggest that memory in networks results from an ongoing interplay between changes in synaptic efficacy and intrinsic membrane properties.

Animals↗
PubMed1996

Ultrastructure of the stomatogastric ganglion neuropil of the crab, Cancer borealis.

The stomatogastric ganglion (STG) of the crab, Cancer borealis, contains the neural networks responsible for rhythmic pattern generation of the foregut. Neuron counts indicate that the STG of C. borealis has 25-26 neurons, 4-5 fewer than that found in lobsters. We describe the ultrastructural features of the ganglion by focusing on those that may be involved in storage, release, or range of action of peptide modulators, including a lacunar system and multiple types of intercellular junctions. In the neuropil, we identify five synaptic profile classes that contain the invertebrate presynaptic apparatus (dense bars, small clear vesicles), two of which also contain dense core (modulator-containing) vesicles. These latter two are comprised of multiple immunocytochemical classes that are not easily distinguished by structural criteria. In addition, we find neurohemal-like profiles that contain primarily dense core vesicles. Our finding that multiple profile types in the STG possess modulator-containing vesicles coincides with immunocytochemical results better than do previous ultrastructural studies that report only one such profile type. We show that a single modulatory input, stomatogastric nerve axon 1, makes only classical synapses and not neurohemal-like profiles, although some modulators are found in both these profile types. These data provide the groundwork for understanding the architecture of modulatory input-target interactions and suggest ways that the specificity of modulatory effects within a complex neuropil may be attained.

Animals↗
PubMed1996

Decoding synapses.

The strength of many synapses is modified by various use and time-dependent processes, including facilitation and depression. A general description of synaptic transfer characteristics must account for the history-dependence of synaptic efficacy and should be able to predict the postsynaptic response to any temporal pattern of presynaptic activity. To generate such a description, we use an approach similar to the decoding method used to reconstruct a sensory input from a neuronal firing pattern. Specifically, a mathematical fit of the postsynaptic response to an isolated action potential is multiplied by an amplitude factor that depends on a time-dependent function summed over all previous presynaptic spikes. The amplitude factor is, in general, a nonlinear function of this sum. Approximate forms of the time-dependent function and the nonlinearity are extracted from the data, and then both functions are constructed more precisely by a learning algorithm. This approach, which should be applicable to a wide variety of synapses, is applied here to several crustacean neuromuscular junctions. After training on data from random spike sequences, the method predicts the postsynaptic response to an arbitrary train of presynaptic action potentials. Using a model synapse, we relate the functions used in the fit to underlying biophysical processes. Fitting different neuromuscular junctions allows us to compare their responses to sequences of action potentials and to contrast the time course and degree of facilitation or depression that they exhibit.

Action Potentials↗
PubMed1996

Neural modulation: following your own rhythm.

Recent studies of an invertebrate neural circuit show how presynaptic inhibition can play a key role in the generation of oscillatory activity, and can allow the directly affected axon terminal to engage in rhythmic activity independently of the rest of the neuron.

Animals↗
PubMed1996

TNRNFLRFamide and SDRNFLRFamide modulate muscles of the stomatogastric system of the crab Cancer borealis.

The effects of the extended FLRFamide-like peptides, TNRNFLRFamide and SDRNFLRFamide, were studied on the stomach musculature of the crab Cancer borealis. Peptide-induced modulation of nerve-evoked contractions was used to screen muscles. All but 2 of the 17 muscles tested were modulated by the peptides. In several muscles of the pyloric region, peptides induced long-lasting myogenic activity. In other muscles, the peptides increased the amplitude of nerve-evoked contractions, excitatory junctional potentials, and excitatory junctional currents, but produced no apparent change in the input resistance of the muscle fibers. The threshold concentration was 10(-10) M for TNRNFLRFamide and between 10(-9) M to 10(-8) M for SDRNFLRFamide. The absence of direct peptide-containing innervation to these muscles and the wide-spread sensitivity of these muscles to the peptides suggest that TNRNFLRFamide and SDRNFLRFamide may be released from neurosecretory structures to modulate stomatogastric musculature hormonally. We speculate that hormonally released peptide will be crucial for maintaining appreciable muscle contraction in response to low-frequency and low-intensity motor discharge.

Animals↗
PubMed1996

Cellular short-term memory from a slow potassium conductance.

1. We use the dynamic clamp to add the slowly inactivating and slowly recovering K+ conductance Kv1.3 to cultured stomatogastric ganglion neurons. 2. Introduction of Kv1.3 produced long delays to firing during depolarization. Additionally, the slow recovery from inactivation produced an increase in neuronal excitability after a depolarizing input that outlasted the input by many seconds. Finally, when introduced into bursting neurons, Kv1.3 produced a long-lasting depolarization-induced switch between tonic and burst firing. 3. These data demonstrate that the slow kinetics of a K+ conductance can produce a form of cellular short-term memory that is independent of any changes in synaptic efficacy.

Action Potentials↗
PubMed1996

Mechanisms of oscillation in dynamic clamp constructed two-cell half-center circuits.

1. The dynamic clamp was used to create reciprocally inhibitory two-cell circuits from pairs of pharmacologically isolated gastric mill neurons of the stomatogastric ganglion of the crab, Cancer borealis. 2. We used this system to study how systematic alterations in intrinsic and synaptic parameters affected the network behavior. This has previously only been possible in purely computational systems. 3. In the absence of additional hyperpolarization-activated inward current (IH), stable half-center oscillatory behavior was not observed. In the presence of additional IH, a variety of circuit dynamics, including stable half-center oscillatory activity, was produced. 4. Stable half-center behavior requires that the synaptic threshold lie within the voltage envelope of the slow wave oscillation. 5. Changes in the synaptic threshold produce dramatic changes in half-center period. As predicted by previous theoretical work, when the synaptic threshold is depolarized, the period first increases and then decreases in a characteristic inverted U-shaped relationship. Analysis of the currents responsible for the transition between the active and inhibited neurons shows that the mechanism of oscillation changes as the synaptic threshold is varied. 6. Increasing the time constant and the conductance of the inhibitory synaptic current increased the period of the half-center oscillator. 7. Increasing the conductance of IH or changing the voltage dependence of IH can either increase or decrease network period, depending on the initial mode of network oscillation. A depolarization of the activation curve causes the network to respond in a similar fashion as increasing the conductance of IH. 8. Many neuromodulatory substances are known to alter synaptic strength and the conductance and voltage dependence of IH, parameters we studied with the dynamic clamp. To understand the response of the network to modulation of a single parameter, it is necessary to understand the nature of the altered conductance and how it interacts with the other conductances in the system.

Action Potentials↗
PubMed1996

Principles of rhythmic motor pattern generation.

Rhythmic movements are produced by central pattern-generating networks whose output is shaped by sensory and neuromodulatory inputs to allow the animal to adapt its movements to changing needs. This review discusses cellular, circuit, and computational analyses of the mechanisms underlying the generation of rhythmic movements in both invertebrate and vertebrate nervous systems. Attention is paid to exploring the mechanisms by which synaptic and cellular processes interact to play specific roles in shaping motor patterns and, consequently, movement.

Animals↗
PubMed1995

Distribution and effects of tachykinin-like peptides in the stomatogastric nervous system of the crab, Cancer borealis.

The rhythmically active pyloric and gastric mill motor patterns in the stomatogastric ganglion of the crab, Cancer borealis, are influenced by modulatory projection neurons whose somata are located primarily in the other ganglia of the stomatogastric nervous system. One of these projection neurons exhibits substance P-like immunolabeling. However, bath application of substance P does not influence these motor patterns. To determine whether a different peptide is responsible for the substance P-like immunolabeling, we studied the presence and physiological effects of the locustatachykinins and the leucokinins, two families of tachykinin-like peptides originally identified in insect nervous systems. Locustatachykinin-like immunolabeling has the same distribution in the stomatogastric nervous system as substance P-like immunolabeling and colocalizes with it in the majority of immunopositive structures. Preincubation of locustatachykinin antibody with substance P, and preincubation of substance P antibody with locustatachykinin, blocks subsequent immunolabeling in the stomatogastric nervous system. In contrast, we found no leucokinin-like immunolabeling in this system. Bath application to the stomatogastric ganglion of individual locustatachykinins or leucokinins excited the pyloric rhythm in a state-dependent manner. Each peptide family had distinct effects on the pyloric rhythm. Thus, both of these tachykinin-like peptide families are likely related to native neuropeptides that influence the pyloric rhythm. Furthermore, a member of the locustatachykinin family is likely to be the source of the previously identified substance P-like immunoreactivity in the stomatogastric nervous system.

Amino Acid Sequence↗
PubMed1995

Functional organization of cotransmission systems: lessons from small nervous systems.

Small invertebrate nervous systems allow one to ask a series of questions concerning the functional roles of cotransmitters. This review outlines some of the implications of cotransmission for target selectivity in complex neuropils. We suggest the possibility that a unique constellation of cotransmitters in individual identified modulatory neurons allows a specificity of action even when peptides may act over an extended distance, and when individual modulatory substances may be released from several modulatory neurons.

Animals↗
PubMed1995

Theory in motion.

Modeling studies are now a significant part of mainstream research in motor control. Novel and classical modeling techniques used in recent work on small and large motor systems illustrate the different roles that models play in furthering our understanding of motor systems. The models presented reveal single neuron short-term memory, unexpected effects of reciprocal inhibition and methods for decoding activity in large populations of neurons.

Animals↗
PubMed1995

Immunocytochemical localization of multiple cholecystokinin-like peptides in the stomatogastric nervous system of the crab Cancer borealis.

Three anti-cholecystokinin antibodies were used to label the stomatogastric nervous system of the crab Cancer borealis. Labeled tissues were examined as whole mounts using laser scanning confocal microscopy. Although each of the anti-cholecystokinin antibodies labeled a variety of structures within the stomatogastric nervous system (including somata, fibers and neuropil), the pattern of labeling produced by each antibody was distinct. These results indicate that there is a family of cholecystokinin-like molecules that are differentially distributed among a subpopulation of the neurons in the stomatogastric nervous system of Cancer borealis.

Animals↗
PubMed1995

Matrix of neuromodulators in neurosecretory structures of the crab Cancer borealis.

The crustacean stomatogastric ganglion, which is situated in the ophthalmic artery, can be modulated by both intrinsically released molecules and hormones. In the crab Cancer borealis, over a dozen neuroactive compounds have been identified in the input axons that project into the stomatogastric neuropil. However, little is known about the modulator content of the two major neurohemal organs, the sinus glands and the pericardial organs, in this crab. We now report the results of a series of immunocytochemical experiments designed to identify putative neurohormones in these tissues. We find that the majority of modulators present in the input axons of the stomatogastric ganglion are also present in at least one of the neurohemal organs. Specifically, allatostatin-like, buccalin-like, cholecystokinin-like, FLRFamide-like, GABA-like, locustatachykinin-like, myomodulin-like, proctolin-like, red pigment concentrating hormone-like and serotonin-like immunoreactivities are all present in both the stomatogastric neuropil and at least one of the neurohemal organs. Thus, these substances are likely to serve a dual role as both local and hormonal modulators of the stomatogastric network. Two other substances, beta-pigment dispersing hormone and crustacean cardioactive peptide, are not present in the stomatogastric neuropil, but beta-pigment dispersing hormone immunoreactivity is present in the sinus glands and crustacean cardioactive peptide immunoreactivity is present in the pericardial organs. It is likely that crustacean cardioactive peptide exerts its influence on the stomatogastric neural circuit via hormonal pathways. Double-labeling experiments show that the patterns of modulator co-localization present in the stomatogastric neuropil are different from those in the neurosecretory organs, suggesting that few rules of colocalization hold across these tissues.

Animals↗