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The Journal of Neuroscience : the... Nov 2023Many neurons exhibit regular firing that is limited to the duration and intensity of depolarizing stimuli. However, some neurons exhibit all-or-nothing plateau...
Many neurons exhibit regular firing that is limited to the duration and intensity of depolarizing stimuli. However, some neurons exhibit all-or-nothing plateau potentials that, once elicited, can lead to prolonged activity that is independent of stimulus intensity or duration. To better understand this diversity of information processing, we compared the voltage-gated and Ca-gated currents of three identified neurons from hermaphroditic Two of these neurons, B51 and B64, generated plateau potentials and a third neuron, B8, exhibited regular firing and was incapable of generating a plateau potential. With the exception of the Ca-gated potassium current ( ), all three neuron types expressed a similar array of outward and inward currents, but with distinct voltage-dependent properties for each neuron type. Inhibiting voltage-gated Ca channels with Ni prolonged the plateau potential, indicating is important for plateau potential termination. In contrast, inhibiting persistent Na ( ) blocked plateau potentials, empirically and in simulations. Surprisingly, the properties and level of expression of were similar in all three neurons, indicating that the presence of does not distinguish between regular-firing neurons and neurons capable of generating plateau potentials. Rather, the key distinguishing factor is the relationship between and outward currents such as the delayed outward current ( ), and We then demonstrated a technique for predicting complex physiological properties such as plateau duration, plateau amplitude, and action potential duration as a function of parameter values, by fitting a curve in parameter space and projecting the curve beyond the tested values. Plateau potentials are intrinsic properties of neurons that are important for information processing in a wide variety of nervous systems. We examined three identified neurons in with different propensities to generate a plateau potential. No single conductance was found to distinguish plateau generating neurons. Instead, plateau generation depended on the ratio between persistent Na current ( ), which favored plateaus, and outward currents such as , which facilitated plateau termination. Computational models revealed a relationship between the individual currents that predicted the features of simulated plateau potentials. These results provide a more solid understanding of the conductances that mediate plateau generation.
Topics: Calcium; Neurons; Action Potentials
PubMed: 37699717
DOI: 10.1523/JNEUROSCI.0789-23.2023 -
Oxford Open Neuroscience 2023Phosphorylation of the MAPK family member extracellular signal-regulated kinase (ERK) is required to induce long-term synaptic plasticity, but little is known about its...
Phosphorylation of the MAPK family member extracellular signal-regulated kinase (ERK) is required to induce long-term synaptic plasticity, but little is known about its persistence. We examined ERK activation by three protocols that induce long-term synaptic facilitation (LTF) of the sensorimotor synapse - the standard protocol (five 5-min pulses of 5-HT with interstimulus intervals (ISIs) of 20 min), the enhanced protocol (five pulses with irregular ISIs, which induces greater and longer-lasting LTF) and the two-pulse protocol (two pulses with ISI 45 min). Immunofluorescence revealed complex ERK activation. The standard and two-pulse protocols immediately increased active, phosphorylated ERK (pERK), which decayed within 5 h. A second wave of increased pERK was detected 18 h post-treatment for all protocols. This late phase was blocked by inhibitors of protein kinase A, TrkB and TGF-β. These results suggest that complex interactions among kinase pathways and growth factors contribute to the late increase of pERK. ERK activity returned to basal 24 h after the standard or two-pulse protocols, but remained elevated 24 h for the enhanced protocol. This 24-h elevation was also dependent on PKA and TGF-β, and partly on TrkB. These results begin to characterize long-lasting ERK activation, plausibly maintained by positive feedback involving growth factors and PKA, that appears essential to maintain LTF and LTM. Because many processes involved in LTF and late LTP are conserved among and mammals, these findings highlight the importance of examining the dynamics of kinase cascades involved in vertebrate long-term memory.
PubMed: 37649778
DOI: 10.1093/oons/kvac014 -
Frontiers in Computational Neuroscience 2023The dynamical properties of the brain and the dynamics of the body strongly influence one another. Their interaction generates complex adaptive behavior. While a wide...
UNLABELLED
The dynamical properties of the brain and the dynamics of the body strongly influence one another. Their interaction generates complex adaptive behavior. While a wide variety of simulation tools exist for neural dynamics or biomechanics separately, there are few options for integrated brain-body modeling. Here, we provide a tutorial to demonstrate how the widely-used NEURON simulation platform can support integrated neuromechanical modeling. As a first step toward incorporating biomechanics into a NEURON simulation, we provide a framework for integrating inputs from a "periphery" and outputs to that periphery. In other words, "body" dynamics are driven in part by "brain" variables, such as voltages or firing rates, and "brain" dynamics are influenced by "body" variables through sensory feedback. To couple the "brain" and "body" components, we use NEURON's construct to share information between "brain" and "body" modules. This approach allows separate specification of brain and body dynamics and code reuse. Though simple in concept, the use of pointers can be challenging due to a complicated syntax and several different programming options. In this paper, we present five different computational models, with increasing levels of complexity, to demonstrate the concepts of code modularity using pointers and the integration of neural and biomechanical modeling within NEURON. The models include: (1) a neuromuscular model of calcium dynamics and muscle force, (2) a neuromechanical, closed-loop model of a half-center oscillator coupled to a rudimentary motor system, (3) a closed-loop model of neural control for respiration, (4) a pedagogical model of a non-smooth "brain/body" system, and (5) a closed-loop model of feeding behavior in the sea hare that incorporates biologically-motivated non-smooth dynamics. This tutorial illustrates how NEURON can be integrated with a broad range of neuromechanical models.
CODE AVAILABLE AT
https://github.com/fietkiewicz/PointerBuilder.
PubMed: 37583894
DOI: 10.3389/fncom.2023.1143323 -
Biomolecules Jun 2023With a single gene encoding H1 channel, proton channel diversity is particularly low in mammals compared to other members of the superfamily of voltage-gated ion... (Review)
Review
With a single gene encoding H1 channel, proton channel diversity is particularly low in mammals compared to other members of the superfamily of voltage-gated ion channels. Nonetheless, mammalian H1 channels are expressed in many different tissues and cell types where they exert various functions. In the first part of this review, we regard novel aspects of the functional expression of H1 channels in mammals by differentially comparing their involvement in (1) close conjunction with the NADPH oxidase complex responsible for the respiratory burst of phagocytes, and (2) in respiratory burst independent functions such as pH homeostasis or acid extrusion. In the second part, we dissect expression of H channels within the eukaryotic tree of life, revealing the immense diversity of the channel in other phylae, such as mollusks or dinoflagellates, where several genes encoding H channels can be found within a single species. In the last part, a comprehensive overview of the biophysical properties of a set of twenty different H channels characterized electrophysiologically, from Mammalia to unicellular protists, is given.
Topics: Animals; Protons; Ion Channels; Cell Membrane; Respiratory Burst; Eukaryota; Mammals
PubMed: 37509071
DOI: 10.3390/biom13071035 -
Learning & Memory (Cold Spring Harbor,... 2023Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been...
Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been hampered by the complexity of the nervous system. The marine mollusk , with a simpler nervous system and many large, identified neurons, presents several advantages for addressing this question and has been used to examine the roles of tens of peptides in behavior. To screen for other peptides that might also play roles in behavior, we observed immunoreactivity in individual neurons in the central nervous system of adult with antisera raised against the peptide FMRFamide and two mammalian peptides that are also found in , cholecystokinin (CCK) and neuropeptide Y (NPY), as well as serotonin (5HT). In addition, we observed staining of individual neurons with antisera raised against mammalian somatostatin (SOM) and peptide histidine isoleucine (PHI). However, genomic analysis has shown that these two peptides are not expressed in the nervous system, and we have therefore labeled the unknown peptides stained by these two antibodies as X and X There was an area at the anterior end of the cerebral ganglion that had staining by antisera raised against many different transmitters, suggesting that this may be a modulatory region of the nervous system. There was also staining for X and, in some cases, FMRFamide in the bag cell cluster of the abdominal ganglion. In addition, these and other studies have revealed a fairly high degree of colocalization of different neuropeptides in individual neurons, suggesting that the peptides do not just act independently but can also interact in different combinations to produce complex functions. The simple nervous system of is advantageous for further testing these ideas.
Topics: Animals; Aplysia; FMRFamide; Central Nervous System; Neuropeptides; Ganglia; Mammals
PubMed: 37442624
DOI: 10.1101/lm.053758.123 -
Frontiers in Neural Circuits 2023Motivated behaviors such as feeding depend on the functional properties of decision neurons to provide the flexibility required for behavioral adaptation. Here, we...
Motivated behaviors such as feeding depend on the functional properties of decision neurons to provide the flexibility required for behavioral adaptation. Here, we analyzed the ionic basis of the endogenous membrane properties of an identified decision neuron (B63) that drive radula biting cycles underlying food-seeking behavior in . Each spontaneous bite cycle arises from the irregular triggering of a plateau-like potential and resultant bursting by rhythmic subthreshold oscillations in B63's membrane potential. In isolated buccal ganglion preparations, and after synaptic isolation, the expression of B63's plateau potentials persisted after removal of extracellular calcium, but was completely suppressed in a tetrodotoxin (TTX)- containing bath solution, thereby indicating the contribution of a transmembrane Na influx. Potassium outward efflux through tetraethylammonium (TEA)- and calcium-sensitive channels was found to contribute to each plateau's active termination. This intrinsic plateauing capability, in contrast to B63's membrane potential oscillation, was blocked by the calcium-activated non-specific cationic current () blocker flufenamic acid (FFA). Conversely, the SERCA blocker cyclopianozic acid (CPA), which abolished the neuron's oscillation, did not prevent the expression of experimentally evoked plateau potentials. These results therefore indicate that the dynamic properties of the decision neuron B63 rely on two distinct mechanisms involving different sub-populations of ionic conductances.
Topics: Animals; Aplysia; Calcium; Sodium; Neurons; Membrane Potentials; Action Potentials
PubMed: 37361713
DOI: 10.3389/fncir.2023.1200902 -
Neuroscience Research Nov 2023Anorexia is a behavioral change caused by functional brain disorders in patients with Alzheimer's disease (AD). Amyloid-β (1-42) oligomers (o-Aβ) are possible...
Administration of amyloid-β oligomer to the buccal ganglia may reduce food intake and cholinergic synaptic responses within the feeding neural circuit in Aplysia kurodai.
Anorexia is a behavioral change caused by functional brain disorders in patients with Alzheimer's disease (AD). Amyloid-β (1-42) oligomers (o-Aβ) are possible causative agents of AD that impair signaling via synaptic dysfunction. In this study, we used Aplysia kurodai to study functional disorders of the brain through o-Aβ. Administration of o-Aβ to the buccal ganglia (feeding brain for oral movements) by surgical treatment significantly reduced food intake for at least five days. Furthermore, we explored the effects of o-Aβ on the synaptic function in the feeding neural circuit, focusing on a specific inhibitory synaptic response in jaw-closing motor neurons produced by cholinergic buccal multi-action neurons because we recently found that this cholinergic response decreases with aging, which is consistent with the cholinergic hypothesis for aging. Administration of o-Aβ to the buccal ganglia significantly reduced the synaptic response within minutes, whereas administration of amyloid-β (1-42) monomers did not. These results suggest that o-Aβ may impair the cholinergic synapses, even in Aplysia, which is consistent with the cholinergic hypothesis for AD.
Topics: Animals; Humans; Amyloid beta-Peptides; Aplysia; Alzheimer Disease; Ganglia; Synapses; Cholinergic Agents; Eating
PubMed: 37328111
DOI: 10.1016/j.neures.2023.06.004 -
International Journal of Molecular... May 2023Amyloids are fibrillar protein aggregates with a cross-β structure. More than two hundred different proteins with amyloid or amyloid-like properties are already known....
Amyloids are fibrillar protein aggregates with a cross-β structure. More than two hundred different proteins with amyloid or amyloid-like properties are already known. Functional amyloids with conservative amyloidogenic regions were found in different organisms. Protein aggregation appears to be beneficial for the organism in these cases. Therefore, this property might be conservative for orthologous proteins. The amyloid aggregates of the CPEB protein were suggested to play an important role in the long-term memory formation in , , and . Moreover, the FXR1 protein demonstrates amyloid properties among the Vertebrates. A few nucleoporins (e.g., yeast Nup49, Nup100, Nup116, and human Nup153 and Nup58), are supposed or proved to form amyloid fibrils. In this study, we performed wide-scale bioinformatic analysis of nucleoporins with FG-repeats (phenylalanine-glycine repeats). We demonstrated that most of the barrier nucleoporins possess potential amyloidogenic properties. Furthermore, the aggregation-prone properties of several Nsp1 and Nup100 orthologs in bacteria and yeast cells were analyzed. Only two new nucleoporins, Nup98 and Nup98, aggregated in different experiments. At the same time, Nup58 only formed amyloids in bacterial cells. These results rather contradict the hypothesis about the functional aggregation of nucleoporins.
Topics: Mice; Animals; Humans; Nuclear Pore Complex Proteins; Saccharomyces cerevisiae; Amyloid; Drosophila melanogaster; Saccharomyces cerevisiae Proteins; Amyloidogenic Proteins; RNA-Binding Proteins; Nuclear Proteins
PubMed: 37239918
DOI: 10.3390/ijms24108571 -
Scientific Reports May 2023Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein...
Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein coupled receptors (GPCRs). Among them, the elevenin signaling system is now believed to be present primarily in protostomes. Although elevenin was first identified from the L11 neuron of the abdominal ganglion in mollusc Aplysia californica, no receptors have been described in Aplysia, nor in any other molluscs. Here, using two elevenin receptors in annelid Platynereis dumerilii, we found three putative elevenin GPCRs in Aplysia. We cloned the three receptors and tentatively named them apElevR1, apElevR2, and apElevR3. Using an inositol monophosphate (IP1) accumulation assay, we demonstrated that Aplysia elevenin with the disulfide bond activated the three putative receptors with low EC50 values (ranging from 1.2 to 25 nM), supporting that they are true receptors for elevenin. In contrast, elevenin without the disulfide bond could not activate the receptors, indicating that the disulfide bond is required for receptor activity. Using alanine substitution of individual conserved residues other than the two cysteines, we showed that these residues appear to be critical to receptor activity, and the three different receptors had different sensitivities to the single residue substitution. Finally, we examined the roles of those residues outside the disulfide bond ring by removing these residues and found that they also appeared to be important to receptor activity. Thus, our study provides an important basis for further study of the functions of elevenin and its receptors in Aplysia and other molluscs.
Topics: Animals; Amino Acid Sequence; Aplysia; Neuropeptides; Receptors, G-Protein-Coupled; Disulfides
PubMed: 37169790
DOI: 10.1038/s41598-023-34596-9 -
Fish & Shellfish Immunology Jun 2023The internal defense system of mollusks represents an efficient protection against pathogens and parasites, involving several biological immune processes, such as...
The internal defense system of mollusks represents an efficient protection against pathogens and parasites, involving several biological immune processes, such as phagocytosis, encapsulation, cytotoxicity, and antigenic recognition of self/non-self. Mollusks possess professional, migratory, and circulating cells that play a key role in the defense of the organism, the hemocytes. Several studies have been performed on hemocytes from different mollusks, but, to date, these cells are still scarcely explored. Different hemocyte populations have been found, according to the presence or absence of granules, size, and the species of mollusks studied. Our study aims to deepen the knowledge of the hemocytes of the gastropod Aplysia depilans using morphological techniques and light and confocal microscopy, testing Toll-like receptor 2, inducible nitric oxide synthetase, and nicotinic acetylcholine receptor alpha 7 subunit. Our results show two hemocyte populations distinguishable by size, and presence/absence of granules in the cytoplasm, strongly positive for the antibodies tested, suggesting for the first time the presence of these receptors on the surface of sea hare hemocytes by immunohistochemistry. These data help in the understanding of the immune system of this gastropod, providing additional data for comprehending the evolution of the defense response in metazoan phylogenesis.
Topics: Animals; Aplysia; Gastropoda; Hemocytes; Mollusca; Phagocytosis
PubMed: 37146849
DOI: 10.1016/j.fsi.2023.108791