Plateau properties in pain pathways.
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Biomedical subjects
Publications and source records attributed to Eve Marder.
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The crustacean stomatogastric ganglion (STG) is modulated by both locally released neuroactive compounds and circulating hormones. This study presents mass spectrometric characterization of the complement of peptide hormones present in one of the major neurosecretory structures, the pericardial organs (POs), and the detection of neurohormones released from the POs. Direct peptide profiling of Cancer borealis PO tissues using matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) revealed many previously identified peptides, including proctolin, red pigment concentrating hormone (RPCH), crustacean cardioactive peptide (CCAP), several orcokinins, and SDRNFLRFamide. This technique also detected corazonin, a well-known insect hormone, in the POs for the first time. However, most mass spectral peaks did not correspond to previously known peptides. To characterize and identify these novel peptides, we performed MALDI postsource decay (PSD) and electrospray ionization (ESI) MS/MS de novo sequencing of peptides fractionated from PO extracts. We characterized a truncated form of previously identified TNRNFLRFamide, NRNFLRFamide. In addition, we sequenced five other novel peptides sharing a common C-terminus of RYamide from the PO tissue extracts. High K+ depolarization of isolated POs released many peptides present in this tissue, including several of the novel peptides sequenced in the current study.
The pericardial organs (POs) are a pair of neurosecretory organs that surround the crustacean heart and release neuromodulators into the hemolymph. In adult crustaceans, the POs are known to contain a wide array of peptide and amine modulators. However, little is known about the modulatory content of POs early in development. We characterize the morphology and modulatory content of pericardial organs in the embryonic lobster, Homarus americanus. The POs are well developed by midway through embryonic (E50) life and contain a wide array of neuromodulatory substances. Immunoreactivities to orcokinin, extended FLRFamide peptides, tyrosine hydroxylase, proctolin, allatostatin, serotonin, Cancer borealis tachykinin-related peptide, cholecystokinin, and crustacean cardioactive peptide are present in the POs by approximately midway through embryonic life. There are two classes of projection patterns to the POs. Immunoreactivities to orcokinin, extended FLRFamide peptides, and tyrosine hydroxylase project solely from the subesophageal ganglion (SEG), whereas the remaining modulators project from the SEG as well as from the thoracic ganglia. Double-labeling experiments with a subset of modulators did not reveal any colocalized peptides in the POs. These results suggest that the POs could be a major source of neuromodulators early in development.
Early neuroscientists scoured the animal kingdom for the ideal preparation with which to study specific problems of interest. Today, non-mammalian nervous systems continue to provide ideal platforms for the study of fundamental problems in neuroscience. Indeed, the peculiarities of body plan and nervous systems that have evolved to carry out precise tasks in unique ecological niches enable investigators not only to pose specific scientific questions, but also to uncover principles that are general to all nervous systems.
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The orcokinins are a family of neuropeptides recently isolated from several crustacean species. We found orcokinin-like immunoreactivity in the stomatogastric nervous systems and pericardial organs of three decapod crustacean species, Homarus americanus, Cancer borealis, and Panulirus interruptus. The neuropil of the stomatogastric ganglion was stained in adults of all three species as well as in embryonic and larval H. americanus. In H. americanus, the somata giving rise to this projection were found in the inferior ventricular nerve. Matrix-assisted laser desorption/ionization mass spectrometry mass profiling and sequencing with postsource decay led to the identification of six different orcokinin family peptides, including those previously described in other decapods and two novel shorter peptides. Application of exogenous [Ala(13)]orcokinin to the stomatogastric ganglion of H. americanus resulted in changes in the pyloric rhythm. Specifically, the number of lateral pyloric (LP) neuron spikes/burst decreased, and the phase of firing of the pyloric neurons was altered. Together, these data indicate that the orcokinins are likely to function as modulators of the crustacean stomatogastric ganglion.
In the presence of descending modulatory inputs, the stomatogastric ganglion (STG) of the lobster Homarus americanus generates a triphasic motor pattern, the pyloric rhythm. Red pigment-concentrating hormone (RPCH) and Cancer borealis tachykinin-related peptide (CabTRP) are colocalized in a pair of fibers that project into the neuropil of the STG. When the STG was isolated from anterior ganglia modulatory inputs, the lateral pyloric (LP) and pyloric (PY) neurons became silent, whereas the anterior burster (AB) and pyloric dilator (PD) neurons were rhythmically active at a low frequency. Exogenous application of 10(-6) m RPCH activated the LP neuron but not the PY neurons; 10(-6) m CabTRP activated the PY neurons but not the LP neuron. The actions of RPCH on the LP neuron and CabTRP on the PY neurons persisted when the rhythmic drive from the PD and AB neurons was removed, suggesting that the LP and PY neurons are direct targets for RPCH and CabTRP respectively. Coapplication of 10(-6) m RPCH and 10(-6) m CabTRP elicited triphasic motor patterns with phase relationships resembling those in a preparation with modulatory inputs intact. In summary, cotransmitters acting on different network targets act cooperatively to activate a complete central pattern-generating circuit.
Individual neurons display characteristic firing patterns determined by the number and kind of ion channels in their membranes. We describe experimental and computational studies that suggest that neurons use activity sensors to regulate the number and kind of ion channels and receptors in their membrane to maintain a stable pattern of activity and to compensate for ongoing processes of degradation, synthesis and insertion of ion channels and receptors. We show that similar neuronal and network outputs can be produced by a number of different combinations of ion channels and synapse strengths. This suggests that individual neurons of the same class may each have found an acceptable solution to a genetically determined pattern of activity, and that networks of neurons in different animals may produce similar output patterns by somewhat variable underlying mechanisms.
Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components.
All network dynamics emerge from the complex interaction between the intrinsic membrane properties of network neurons and their synaptic connections. Nervous systems contain numerous amines and neuropeptides that function to both modulate the strength of synaptic connections and the intrinsic properties of network neurons. Consequently network dynamics can be tuned and configured in different ways, as a function of the actions of neuromodulators. General principles of the organization of modulatory systems in nervous systems include: (a) many neurons and networks are multiply modulated, (b) there is extensive convergence and divergence in modulator action, and (c) some modulators may be released extrinsically to the modulated circuit, while others may be released by some of the circuit neurons themselves, and act intrinsically. Some of the computational consequences of these features of modulator action are discussed.