scholarly journals The molecular underpinnings of neuronal cell identity in the stomatogastric ganglion of cancer borealis

2019 ◽  
Author(s):  
◽  
Adam Jared Northcutt

Throughout the life of an organism, the nervous system must be able to balance changing in response to environmental stimuli with the need to produce reliable, repeatable activity patterns to create stereotyped behaviors. Understanding the mechanisms responsible for this regulation requires a wealth of knowledge about the neural system, ranging from network connectivity and cell type identification to intrinsic neuronal excitability and transcriptomic expression. To make strides in this area, we have employed the well-described stomatogastric nervous system of the Jonah crab Cancer borealis to examine the molecular underpinnings and regulation of neuron cell identity. Several crustacean circuits, including the stomatogastric nervous system and the cardiac ganglion, continue to provide important new insights into circuit dynamics and modulation (Diehl, White, Stein, and Nusbaum, 2013; Marder, 2012; Marder and Bucher, 2007; Williams et al., 2013), but this work has been partially hampered by the lack of extensive molecular sequence knowledge in crustaceans. Here we generated de novo transcriptome assembly from central nervous system tissue for C. borealis producing 42,766 contigs, focusing on an initial identification, curation, and comparison of genes that will have the most profound impact on our understanding of circuit function in these species. This included genes for 34 distinct ion channel types, 17 biogenic amine and 5 GABA receptors, 28 major transmitter receptor subtypes including glutamate and acetylcholine receptors, and 6 gap junction proteins -- the Innexins. ... With this reference transcriptome and annotated sequences in hand, we sought to determine the strengths and limitations of using the neuronal molecular profile to classify them into cell types. ... Since the resulting activity of a neuron is the product of the expression of ion channel genes, we sought to further probe the expression profile of neurons across a range of cell types to understand how these patterns of mRNA abundance relate to the properties of individual cell types. ... Finally, we sought to better understand the molecular underpinnings of how these correlated patterns of mRNA expression are generated and maintained.

2017 ◽  
Vol 18 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Andres Morales La Madrid ◽  
Mark W. Kieran

Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages –not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the “classic” current therapeutic approaches. Demographic, radiologic and morphological characterization have several limitations, putting into the “classic boxes” heterogeneous tumors that are diverse in their genetic and epigenetic background and that will likely behave biologically different. Given that, epigenetic disruption (i.e. DNA methylation, histone modification and chromatin remodeling) is a common feature identified more and more frequently in pediatric cancer, it is logical to speculate that interrogating epigenetic marks may help to further define the molecular profile, and therefore tumor biology, evolution and treatment of these tumors. An integrated approach that incorporates traditional features complemented with genetic and epigenenetic specific markers offers tremendous promise to “risk-group” stratification and better prognostication. Also, it will help unveil the key driver pathways for tumor formation and for the discovery of targeted therapy for neoplasms that appear in the developing brain, facilitating early identification of therapy responders and track accurately disease progression. In this paper, we reviewed the most representative pediatric brain tumors where epigenetic alterations have been identified as initiating or driving events in tumor development, maintenance or progression.


1995 ◽  
Vol 354 (2) ◽  
pp. 282-294 ◽  
Author(s):  
Dawn M. Blitz ◽  
Andrew E. Christie ◽  
Eve Marder ◽  
Michael P. Nusbaum

2006 ◽  
Vol 110 (2) ◽  
pp. 175-191 ◽  
Author(s):  
Shelley J. Allen ◽  
David Dawbarn

The neurotrophins are growth factors required by discrete neuronal cell types for survival and maintenance, with a broad range of activities in the central and peripheral nervous system in the developing and adult mammal. This review examines their role in diverse disease states, including Alzheimer's disease, depression, pain and asthma. In addition, the role of BDNF (brain-derived neurotrophic factor) in synaptic plasticity and memory formation is discussed. Unlike the other neurotrophins, BDNF is secreted in an activity-dependent manner that allows the highly controlled release required for synaptic regulation. Evidence is discussed which shows that sequestration of NGF (nerve growth factor) is able to reverse symptoms of inflammatory pain and asthma in animal models. Both pain and asthma show an underlying pathophysiology linked to increases in endogenous NGF and subsequent NGF-dependent increase in BDNF. Conversely, in Alzheimer's disease, there is a role for NGF in the treatment of the disease and a recent clinical trial has shown benefit from its exogenous application. In addition, reductions in BDNF, and changes in the processing and usage of NGF, are evident and it is possible that both NGF and BDNF play a part in the aetiology of the disease process. This highly selective choice of functions and disease states related to neurotrophin function, although in no way comprehensive, illustrates the importance of the neurotrophins in the brain, the peripheral nervous system and in non-neuronal tissues. Ways in which the neurotrophins, their receptors or agonists/antagonists may act therapeutically are discussed.


Parasitology ◽  
1996 ◽  
Vol 113 (S1) ◽  
pp. S47-S72 ◽  
Author(s):  
D. W. Halton ◽  
M. K. S. Gustafsson

SUMMARYAs the most primitive metazoan phylum, the Platyhelminthes occupies a unique position in nervous system evolution. Centrally, their nervous system consists of an archaic brain from which emanate one or more pairs of longitudinal nerve cords connected by commissures; peripherally, a diverse arrangement of nerve plexuses of varying complexity innervate the subsurface epithelial and muscle layers, and in the parasitic taxa they are most prominent in the musculature of the attachment organs and egg-forming apparatus. There is a range of neuronal-cell types, the majority being multi- and bipolar. The flatworm neuron is highly secretory and contains a heterogeneity of vesicular inclusions, dominated by densecored vesicles, whose contents may be released synaptically or by paracrine secretion for presumed delivery to target cells via the extracellular matrix. A wide range of sense organ types is present in flatworms, irrespective of life-styles. The repertoire of neuronal substances identified cytochemically includes all of the major candidate transmitters known in vertebrates. Two groups of native flatworm neuropeptides have been sequenced, neuropeptide F and FMRFamide-related peptides (FaRPs), and immunoreactivities for these have been localised in dense-cored neuronal vesicles in representatives of all major fiatworm groups. There is evidence of co-localisation of peptidergic and cholinergic elements; serotoninergic components generally occupy a separate set of neurons. The actions of neuronal substances in flatworms are largely undetermined, but FaRPs and 5-HT are known to be myoactive in all of the major groups, and there is immuno-cytochemical evidence that they have a role in the mechanism of egg assembly.


Author(s):  
Davis Grininger ◽  
John T. Birmingham

Neuromodulatory actions that change the properties of proprioceptors or the muscle movements to which they respond necessarily affect the feedback provided to the central network. Here we further characterize the responses of the gastropyloric receptor 1 (GPR1) and gastropyloric receptor 2 (GPR2) neurons in the stomatogastric nervous system of the crab Cancer borealis to movements and contractions of muscles, and we report how neuromodulation modifies those responses. We observed that the GPR1 response to contractions of the gastric mill 4 (gm4) muscle was absent, or nearly so, when the neuron was quiescent but robust when it was spontaneously active. We also found that the effects of four neuromodulatory substances (GABA, serotonin, proctolin and TNRNFLRFamide) on the GPR1 response to muscle stretch were similar to those previously reported for GPR2. Finally, we showed that an excitatory action on gm4 due to proctolin combined with an inhibitory action on GPR2 due to GABA can allow for larger muscle contractions without increased proprioceptive feedback.


2000 ◽  
Vol 203 (14) ◽  
pp. 2075-2092 ◽  
Author(s):  
A.M. Swensen ◽  
J. Golowasch ◽  
A.E. Christie ◽  
M.J. Coleman ◽  
M.P. Nusbaum ◽  
...  

The multifunctional neural circuits in the crustacean stomatogastric ganglion (STG) are influenced by many small-molecule transmitters and neuropeptides that are co-localized in identified projection neurons to the STG. We describe the pattern of gamma-aminobutyric acid (GABA) immunoreactivity in the stomatogastric nervous system of the crab Cancer borealis and demonstrate biochemically the presence of authentic GABA in C. borealis. No STG somata show GABA immunoreactivity but, within the stomatogastric nervous system, GABA immunoreactivity co-localizes with several neuropeptides in two identified projection neurons, the modulatory proctolin neuron (MPN) and modulatory commissural neuron 1 (MCN1). To determine which actions of these neurons are evoked by GABA, it is necessary to determine the physiological actions of GABA on STG neurons. We therefore characterized the response of each type of STG neuron to focally applied GABA. All STG neurons responded to GABA. In some neurons, GABA evoked a picrotoxin-sensitive depolarizing, excitatory response with a reversal potential of approximately −40 mV. This response was also activated by muscimol. In many STG neurons, GABA evoked inhibitory responses with both K(+)- and Cl(−)-dependent components. Muscimol and beta-guanidinopropionic acid weakly activated the inhibitory responses, but many other drugs, including bicuculline and phaclofen, that act on vertebrate GABA receptors were not effective. In summary, GABA is found in projection neurons to the crab STG and can evoke both excitatory and inhibitory actions on STG neurons.


1989 ◽  
Vol 62 (2) ◽  
pp. 558-570 ◽  
Author(s):  
P. S. Katz ◽  
M. H. Eigg ◽  
R. M. Harris-Warrick

1. Serotonin (5-hydroxytryptamine) immunohistochemistry was used to locate and anatomically describe a set of four muscle receptor cells in the stomatogastric nervous system of the crabs Cancer borealis and Cancer irroratus. We found that these sensory cells, which we named gastropyloric receptor (GPR) cells, are the sole source of serotonergic inputs to the stomatogastric ganglion (STG) in these species. Thus any endogenous serotonergic modulation of the central pattern generators (CPGs) in the STG must be afferent and not descending from other ganglia. 2. There are two bilateral pairs of GPR cells. Each pair consists of two cell types (GPR1 and GPR2) based on differences in muscle innervation and physiological response characteristics. GPR2 responds in a mostly tonic fashion to increases in muscle tension caused by passive stretch or motor neuron-evoked contraction, whereas GPR1 responds more phasically and adapts more rapidly. Both GPR cell types project to the midline STG and terminate in each of the bilaterally paired commissural ganglia (COGs). 3. The GPR cells have sensory endings unlike any described for other muscle receptor cells: the terminals enter invaginations of the muscle surface and end near the z-bands of the muscle. These novel structures may be involved in the sensory transduction process. 4. The GPR cells may contain acetylcholine in addition to serotonin, as indicated by the presence of choline acetyltransferase (ChAT) in GPR2 (Table 1) and probably GPR1 as well. 5. The GPR cells have no direct effect on muscle properties or neuromuscular transmission: excitatory junctional potential (EJP) amplitude and motor neuron-evoked tension are unaffected by GPR stimulation. However, very low concentrations of exogenously applied serotonin do cause an increase in motor neuron-evoked muscle tension, probably reflecting a hormonal action of the amine. 6. The activity of GPR2 was monitored in a semi-intact preparation. GPR2 is active in phase with normal movements of the gastric mill. GPR2 is also capable of endogenous rhythmic activity. This indicates that even in the absence of mechanical stimulation, the GPR cells may still provide patterned input to the CPGs in the STG. 7. The GPR cells are proprioceptive cells that use serotonin and acetylcholine as cotransmitters. It is important to characterize these cells to understand the role of serotonergic modulation in the production of motor programs by stomatogastric CPGs.


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