-
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 -
Food Chemistry. Molecular Sciences Jul 2023Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout...
Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.
PubMed: 36582744
DOI: 10.1016/j.fochms.2022.100155 -
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 -
Journal of Proteome Research Oct 2023Protein database search engines are an integral component of mass spectrometry-based peptidomic analyses. Given the unique computational challenges of peptidomics, many...
Protein database search engines are an integral component of mass spectrometry-based peptidomic analyses. Given the unique computational challenges of peptidomics, many factors must be taken into consideration when optimizing search engine selection, as each platform has different algorithms by which tandem mass spectra are scored for subsequent peptide identifications. In this study, four different database search engines, PEAKS, MS-GF+, OMSSA, and X! Tandem, were compared with and peptidomics data sets, and various metrics were assessed such as the number of unique peptide and neuropeptide identifications, and peptide length distributions. Given the tested conditions, PEAKS was found to have the highest number of peptide and neuropeptide identifications out of the four search engines in both data sets. Furthermore, principal component analysis and multivariate logistic regression were employed to determine whether specific spectral features contribute to false C-terminal amidation assignments by each search engine. From this analysis, it was found that the primary features influencing incorrect peptide assignments were the precursor and fragment ion / errors. Finally, an assessment employing a mixed species protein database was performed to evaluate search engine precision and sensitivity when searched against an enlarged search space containing human proteins.
Topics: Humans; Animals; Rats; Search Engine; Peptides; Algorithms; Tandem Mass Spectrometry; Neuropeptides; Databases, Protein; Software
PubMed: 36809008
DOI: 10.1021/acs.jproteome.2c00307 -
HardwareX Dec 2023The California sea hare () provides a powerful biomedical model system for studying aspects of neurological development and damage, behavior, aging, and hypoxia....
Untangling the Gordian Knot of sea hare egg masses: An integrated open-hardware system for standardized egg strand sizing and packaging for cryopreservation research and application.
The California sea hare () provides a powerful biomedical model system for studying aspects of neurological development and damage, behavior, aging, and hypoxia. encapsulate their zygotes within strands that result in tangled egg masses that greatly complicate culture and experimentation. The historical and current importance of for biomedical research and the mounting climate crisis necessitates protection of genetic resources. The goal of this work was to prototype open-hardware sizing, processing, and packaging devices for early life stages suitable for integration into a cryopreservation pathway. The Strand Centi-Sizer was a low-cost, fused filament fabrication 3-D printable device that increased experiment preparation efficiency and standardized the cutting of egg strands customizable to user needs. A downstream system of 3-D printed devices was also prototyped to address inefficiencies in handling of egg strand sections for processing and packaging into existing cryopreservation straw platforms. Time studies were conducted comparing manual methods (i.e., no specialized equipment) with open hardware to demonstrate utility of the devices and to encourage community members to design and prototype new devices to address recurrent and novel problems in other aquatic animals that produce egg strands. Improvements in design could further increase efficiency, standardization, and reproducibility, and extend the application of these devices to other research communities, such as shrimp or salamander spermatophores, sea anemone body part (e.g., pedal lacerate) cryopreservation, or study areas such as vitrification.
PubMed: 38020540
DOI: 10.1016/j.ohx.2023.e00476 -
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 -
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 -
Frontiers in Behavioral Neuroscience 2023The transcription factor CCAAT/enhancer binding protein () is expressed as an immediate early gene in the cAMP responsive element binding protein (CREB) mediated gene...
The transcription factor CCAAT/enhancer binding protein () is expressed as an immediate early gene in the cAMP responsive element binding protein (CREB) mediated gene cascade, and it has essential functions in the synaptic consolidation of memory following a learning event. Synaptic consolidation primarily involves morphological changes at neuronal synapses, which are facilitated through the reorganization of the actin and microtubular cytoarchitecture of the cell. During early nervous system development, the transmembrane synaptic protein teneurin acts directly upon neuronal presynaptic microtubules and postsynaptic spectrin-based cytoskeletons to facilitate the creation of new synapses. It is reasonable to hypothesize that may also be linked to learning-induced synaptic changes and is a potential candidate to be a later gene expressed in the CREB-mediated gene cascade downstream of . To assess the role of and in learning and memory in the marine snail , young (age 7-8 months) and aged (age 13-15 months; aging stage AII) siblings of Aplysia were trained in an operant conditioning paradigm-learning food is inedible (LFI)-over 2 days, during which they learned to modify the feeding reflex. Aged had enhanced performance of the LFI task on the second day than younger siblings although far more aged animals were excluded from the analysis because of the initial failure in learning to recognize the inedible probe. After 2 days of training, mRNA and mRNA were quantified in selected neurons of the buccal ganglia, the locus of neural circuits in LFI. expression was elevated in aged compared to young siblings regardless of training. expression was significantly higher in untrained aged animals than in untrained young siblings but decreased in trained aged animals compared to untrained aged animals. Elevated levels of and mRNA before training may have contributed to the enhancement of LFI performance in the aged animals that successfully learned.
PubMed: 37936650
DOI: 10.3389/fnbeh.2023.1221794 -
Scientific Reports Mar 2024Magnetic fields are widely used for neuromodulation in clinical settings. The intended effect of magnetic stimulation is that neural activity resumes its pre-stimulation...
Magnetic fields are widely used for neuromodulation in clinical settings. The intended effect of magnetic stimulation is that neural activity resumes its pre-stimulation state right after stimulation. Many theoretical and experimental works have focused on the cellular and molecular basis of the acute neural response to magnetic field. However, effects of magnetic stimulation can still last after the termination of the magnetic stimulation (named "carry-over effects"), which could generate profound effects to the outcome of the stimulation. However, the cellular and molecular mechanisms of carry-over effects are largely unknown, which renders the neural modulation practice using magnetic stimulation unpredictable. Here, we investigated carry-over effects at the cellular level, using the combination of micro-magnetic stimulation (µMS), electrophysiology, and computation modeling. We found that high frequency magnetic stimulation could lead to immediate neural inhibition in ganglion neurons from Aplysia californica, as well as persistent, carry-over inhibition after withdrawing the magnetic stimulus. Carry-over effects were found in the neurons that fired action potentials under a variety of conditions. The carry-over effects were also observed in the neurons when the magnetic field was applied across the ganglion sheath. The state of the neuron, specifically synaptic input and membrane potential fluctuation, plays a significant role in generating the carry-over effects after magnetic stimulation. To elucidate the cellular mechanisms of such carry-over effects under magnetic stimulation, we simulated a single neuron under magnetic stimulation with multi-compartment modeling. The model successfully replicated the carry-over effects in the neuron, and revealed that the carry-over effect was due to the dysfunction of the ion channel dynamics that were responsible for the initiation and sustaining of membrane excitability. A virtual voltage-clamp experiment revealed a compromised Na conductance and enhanced K conductance post magnetic stimulation, rendering the neurons incapable of generating action potentials and, therefore, leading to the carry over effects. Finally, both simulation and experimental results demonstrated that the carry-over effects could be controlled by disturbing the membrane potential during the post-stimulus inhibition period. Delineating the cellular and ion channel mechanisms underlying carry-over effects could provide insights to the clinical outcomes in brain stimulation using TMS and other modalities. This research incentivizes the development of novel neural engineering or pharmacological approaches to better control the carry-over effects for optimized clinical outcomes.
Topics: Neurons; Membrane Potentials; Action Potentials; Ion Channels; Magnetic Phenomena; Electric Stimulation
PubMed: 38431662
DOI: 10.1038/s41598-024-55915-8 -
Journal of Neuroscience Methods Apr 2024To study neural control of behavior, intracellular recording and stimulation of many neurons in freely moving animals would be ideal. However, current technologies limit...
BACKGROUND
To study neural control of behavior, intracellular recording and stimulation of many neurons in freely moving animals would be ideal. However, current technologies limit the number of neurons that can be monitored and manipulated. A new technology has become available for intracellular recording and stimulation which we demonstrate in the tractable nervous system of Aplysia.
NEW METHOD
Carbon fiber electrode arrays (whose tips are coated with platinum-iridium) were used with an in vitro feeding preparation to intracellularly record from and to control the activity of multiple neurons during feeding movements.
RESULTS
In an in vitro feeding preparation, the carbon fiber electrode arrays recorded action potentials and subthreshold synaptic potentials during feeding movements. Depolarizing or hyperpolarizing currents activated or inhibited identified neurons (respectively), manipulating the movements of the feeding apparatus.
COMPARISON WITH EXISTING METHOD(S)
Standard glass microelectrodes that are commonly used for intracellular recording are stiff, liable to break in response to movement, and require many micromanipulators to be precisely positioned. In contrast, carbon fiber arrays are less sensitive to movement, but are capable of multiple channels of intracellular recording and stimulation.
CONCLUSIONS
Carbon fiber arrays are a novel technology for intracellular recording that can be used in moving preparations. They can record both action potentials and synaptic activity in multiple neurons and can be used to stimulate multiple neurons in complex patterns.
Topics: Animals; Carbon Fiber; Aplysia; Neurons; Microelectrodes; Action Potentials
PubMed: 38336092
DOI: 10.1016/j.jneumeth.2024.110077