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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 217 records · Page 12
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Characterizing and controlling CRISPR repair outcomes in nondividing human cells

Genome editing is poised to revolutionize treatment of genetic diseases, but poor understanding and control of DNA repair outcomes hinders its therapeutic potential. DNA repair is especially understudied in nondividing cells like neurons, limiting the efficiency and precision of genome editing in many clinically relevant tissues. Here, we address this barrier by using induced pluripotent stem cells (iPSCs) and iPSC-derived neurons to examine how postmitotic human neurons repair Cas9-induced DNA damage. CRISPR editing outcomes differ dramatically in neurons compared to genetically identical dividing cells: neurons take longer to fully resolve this damage, and upregulate non-canonical DNA repair factors in the process. Manipulating this response with chemical or genetic perturbations allows us to direct DNA repair toward desired editing outcomes in nondividing human neurons, cardiomyocytes, and primary T cells. By studying DNA repair in clinically relevant cells, we reveal unforeseen challenges and opportunities for precise therapeutic editing.

Ramadoss, Gokul N. [Gladstone Institutes, San Fran↗
DOE OSTI2024

Whole nervous system expression of glutamate receptors reveals distinct receptor roles in sensorimotor circuits

A goal of connectomics is to reveal the links between neural circuits and behavior. Larvae of the primitive chordateCionaare well-suited to make contributions in this area. In addition to having a described connectome,Cionalarvae have a range of readily-quantified behaviors. Moreover, the small number of neurons in the larval CNS (∼180) holds the promise of a comprehensive characterization of individual neurons. We present single-neuron predictions for glutamate receptor (GlutR) expression based onin situhybridization. Included are both ionotropic receptors (AMPA, NMDA, and Kainate), and metabotropic receptors. The predicted glutamate receptor expression dataset is discussed in the context of known circuits driving behaviors such as phototaxis, mechanosensation, and looming shadow response. The predicted expression of AMPA and NMDA receptors may help to resolve issues regarding the co-production of GABA and glutamate by a subset of photoreceptors. The targets of these photoreceptors in the midbrain appear to express NMDA receptors, but not AMPA receptors. This is in agreement with previous results indicating that GABA is the primary neurotransmitter from the photoreceptors evoking a swimming response through a disinhibition mechanism, and that glutamate may, therefore, have only a modulatory action in this circuit. Other findings reported here are more unexpected. For example, many of the targets of glutamatergic epidermal sensory neurons (ESNs) do not express any of the ionotropic receptors, yet the ESNs themselves express metabotropic receptors. Thus, we speculate that their production of glutamate may be for communication with neighboring ESNs, rather than to their interneuron targets. Significance StatementSimple invertebrates offer a tractable alternative to complex vertebrate brains, facilitating holistic understanding of brain function. One such invertebrate is the marine chordateCiona, which has the benefit of a complete synaptic wiring diagram for its swimming larva. This “connectome” allowed identification of putative neural circuits driving defined behaviors. Fuller understanding of neural circuits, however, requires a description of the attributes of individual neurons. This study focuses on the excitatory neurotransmitter glutamate, which signals via a complex set of both ionotropic and metabotropic receptors. Here, we present a nervous system-wide prediction of GlutR expression inCionaat the individual neuron level, considered in the context of neural circuits, with emphasis on how GlutR expression accounts for function of neural circuits.

Neurosciences & Neurology↗
NASA NTRS1995

In vitro thermosensitivity of the midline thalamus

This study compared the thermosensitivity and spontaneous activity of thatamic midline neurons with those of neurons in areas widely regarded to be involved in thermoregulation (preoptic/anterior hypothalamus and posterior hypothalamus). In vitro single unit recordings were made from neurons within the thalamic midline nuclei, the preoptic/anterior hypothalamus and posterior hypothalamus prior to and during a temperature change 3-7 C above and below 37 C. There were no significant differences in the degree of thermosensitivity or the proportion of thermosensitive neurons in the three areas. In each area examined, the thermosensitive neurons had a spontaneous activity which was significantly greater than that of the temperature-insensitive neurons. The results suggest that structures of the midline thalamus may play a role similar to that of the preoptic/anterior hypothalamus and posterior hypothalamus in the processing of temperature related information.

Travis, Kathleen A.↗
NASA NTRS2003

Investigation of Neural Strategies of Visual Search

The goal of this project was to measure how neurons in the superior colliculus (SC) change their activity during a visual search task. Specifically, we proposed to measure how the activity of these neurons was altered by the discriminability of visual targets and to test how these changes might predict the changes in the subjects performance. The primary rationale for this study was that understanding how the information encoded by these neurons constrains overall search performance would foster the development of better models of human performance. Work performed during the period supported by this grant has achieved these aims. First, we have recorded from neurons in the superior colliculus (SC) during a visual search task in which the difficulty of the task and the performance of the subject was systematically varied. The results from these single-neuron physiology experiments shows that prior to eye movement onset, the difference in activity across the ensemble of neurons reaches a fixed threshold value, reflecting the operation of a winner-take-all mechanism. Second, we have developed a model of eye movement decisions based on the principle of winner-take-all . The model incorporates the idea that the overt saccade choice reflects only one of the multiple saccades prepared during visual discrimination, consistent with our physiological data. The value of the model is that, unlike previous models, it is able to account for both the latency and the percent correct of saccade choices.

Krauzlis, Richard J.↗
NASA NTRS2003

The Effect of Spaceflight on the Ultrastructure of the Cerebellum

In weightlessness, astronauts and cosmonauts may experience postural illusions as well as motion sickness symptoms known as the space adaptation syndrome. Upon return to Earth, they have irregularities in posture and balance. The adaptation to microgravity and subsequent re-adaptation to Earth occurs over several days. At the cellular level, a process called neuronal plasticity may mediate this adaptation. The term plasticity refers to the flexibility and modifiability in the architecture and functions of the nervous system. In fact, plastic changes are thought to underlie not just behavioral adaptation, but also the more generalized phenomena of learning and memory. The goal of this experiment was to identify some of the structural alterations that occur in the rat brain during the sensory and motor adaptation to microgravity. One brain region where plasticity has been studied extensively is the cerebellar cortex-a structure thought to be critical for motor control, coordination, the timing of movements, and, most relevant to the present experiment, motor learning. Also, there are direct as well as indirect connections between projections from the gravity-sensing otolith organs and several subregions of the cerebellum. We tested the hypothesis that alterations in the ultrastructural (the structure within the cell) architecture of rat cerebellar cortex occur during the early period of adaptation to microgravity, as the cerebellum adapts to the absence of the usual gravitational inputs. The results show ultrastructural evidence for neuronal plasticity in the central nervous system of adult rats after 24 hours of spaceflight. Qualitative studies conducted on tissue from the cerebellar cortex (specifically, the nodulus of the cerebellum) indicate that ultrastructural signs of plasticity are present in the cerebellar zones that receive input from the gravity-sensing organs in the inner ear (the otoliths). These changes are not observed in this region in cagematched ground control animals. The specific changes include the formation of lamellar bodies, profoundly enlarged Purkinje cell mitochondria, the presence of inter-neuronal cellular protrusions in the molecular layer, and signs of degeneration in the distal dendrites of the Purkinje cells. Since these morphologic signs are not apparent in the control animals, they are not likely to be due to caging or tissue processing effects. The particular nature of the structural alterations in the nodulus, most notably the formation of lamellar bodies and the presence of degeneration, further suggests that excitotoxicity (damaging overstimulation of neurons) may play a role in the short-term neural response to spaceflight. These findings suggest a structural basis for the neuronal and synaptic plasticity accompanying the central nervous system response to altered gravity and help identify the cellular bases underlying the vestibular abnormalities experienced by astronauts during periods of adaptation and re-adaptation to different gravitational forces. Also, since the short- and long-term changes in neural structure occurring during such periods of adaptation resemble the neuronal alterations that occur in some neurologic disorders such as stroke, these findings may offer guidance in the development of strategies for rehabilitation and treatment of such disorders.

Holstein, Gay R.↗
NASA NTRS2001

Bit-serial neuroprocessor architecture

A neuroprocessor architecture employs a combination of bit-serial and serial-parallel techniques for implementing the neurons of the neuroprocessor. The neuroprocessor architecture includes a neural module containing a pool of neurons, a global controller, a sigmoid activation ROM look-up-table, a plurality of neuron state registers, and a synaptic weight RAM. The neuroprocessor reduces the number of neurons required to perform the task by time multiplexing groups of neurons from a fixed pool of neurons to achieve the successive hidden layers of a recurrent network topology.

Tawel, Raoul↗
NASA NTRS2001

Optimal firing rate estimation

We define a measure for evaluating the quality of a predictive model of the behavior of a spiking neuron. This measure, information gain per spike (Is), indicates how much more information is provided by the model than if the prediction were made by specifying the neuron's average firing rate over the same time period. We apply a maximum Is criterion to optimize the performance of Gaussian smoothing filters for estimating neural firing rates. With data from bullfrog vestibular semicircular canal neurons and data from simulated integrate-and-fire neurons, the optimal bandwidth for firing rate estimation is typically similar to the average firing rate. Precise timing and average rate models are limiting cases that perform poorly. We estimate that bullfrog semicircular canal sensory neurons transmit in the order of 1 bit of stimulus-related information per spike.

NASA Discipline Neuroscience↗
DOE OSTI2026

An Atom-Precise Approach to Damp First-Order Phase Transitions and Its Implications for Neuromorphic Signal Processing

Neuromorphic computing inspired by mammalian intelligence aims to emulate the nonlinear dynamics of biological neurons and synapses to achieve fast, low-energy, and highly efficient information processing. Brain-inspired computing relies on the design and discovery of materials exhibiting nonlinear current–voltage profiles, frequently underpinned by electronic state transitions, to achieve spiking neurons and dynamically tunable synapses. A signature challenge in the design of artificial neurons is controlling the steepness of first-order transitions in active elements, as abrupt transitions are at risk of driving unstable voltage and temperature oscillations, which result in catastrophic device failure. A critical knowledge gap is the lack of structure–function correlations mapping the composition and atomistic structure of crystalline solids to nonlinear dynamical response characteristics. Here, we address the key question of how modification of atomistic structure correlates with alteration of neuron-like functionality. Constructing oscillator circuits from millimeter-scale single crystals enables high-resolution atomic structure solutions, which we use to demonstrate that the selective positioning of Pb cations modifies charge ordering along a one-dimensional CuxV2O5 framework even at low insertion stoichiometries, thereby providing an atom-precise design parameter for damping first-order transitions. We use temperature-variant X-ray diffraction and X-ray spectroscopy to elucidate the suppression of Cu-ion shuttling based on the precise positioning of Pb ions in seven-coordinated tunnel interstitial sites as the mechanistic basis for transition broadening, thus bridging a critical gap between statistical mechanics and quantum chemical descriptions of phase transitions. Such mechanistic understanding thus paves the way to site-selective modification strategies for modulating the sharpness of first-order transitions, with an exemplary demonstration here in tuning neuronal signal processing.

Crystal structure↗
DOE OSTI2024

Personalized whole-brain neural mass models reveal combined Aβ and tau hyperexcitable influences in Alzheimer's disease.

Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-β (Aβ) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aβ and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aβ-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1985

Sensory and motor properties of the cerebellar uvula and modulus

The uvula and nodulus (vermal lobules 9 and 10) of the vestibulocerebellum are implicated by behavioral evidence in the control of eye and head movements and in the production of motion sickness. The uvula and nodulus could play a role in these functions through known output pathways. Purkinje cells in both structures project via the fastigial and vestibular nuceli to the ventral horn of the cervical spin cord, to oculomotor neurons, and to the emetic region of the reticular formation (ablation of which abolishes susceptability to motion sickness). Uvula and nodulus Purkinje cells will be analyzed in cats trained to make controlled head movements. The activity of these neurons is expected to modulate well during head and/or eye movements because the uvula and nodulus receive heavy projections from sources of visual, vestibular and neck proprioceptive information. How neuron activity contributes to movement and how different sensory inputs converge to influence this contribution may be determined by characterizing movement related properties of these neurons. A population of neurons that modulates powerfully to the conflict between different head movement signals that can cause motion sickness may be identified.

Robinson, F. R.↗
NASA NTRS1991

Electronic neural network for dynamic resource allocation

A VLSI implementable neural network architecture for dynamic assignment is presented. The resource allocation problems involve assigning members of one set (e.g. resources) to those of another (e.g. consumers) such that the global 'cost' of the associations is minimized. The network consists of a matrix of sigmoidal processing elements (neurons), where the rows of the matrix represent resources and columns represent consumers. Unlike previous neural implementations, however, association costs are applied directly to the neurons, reducing connectivity of the network to VLSI-compatible 0 (number of neurons). Each row (and column) has an additional neuron associated with it to independently oversee activations of all the neurons in each row (and each column), providing a programmable 'k-winner-take-all' function. This function simultaneously enforces blocking (excitatory/inhibitory) constraints during convergence to control the number of active elements in each row and column within desired boundary conditions. Simulations show that the network, when implemented in fully parallel VLSI hardware, offers optimal (or near-optimal) solutions within only a fraction of a millisecond, for problems up to 128 resources and 128 consumers, orders of magnitude faster than conventional computing or heuristic search methods.

Thakoor, A. P.↗
NASA NTRS1990

Identification of the connections in biologically inspired neural networks

We developed an identification method to find the strength of the connections between neurons from their behavior in small biologically-inspired artificial neural networks. That is, given the network external inputs and the temporal firing pattern of the neurons, we can calculate a solution for the strengths of the connections between neurons and the initial neuron activations if a solution exists. The method determines directly if there is a solution to a particular neural network problem. No training of the network is required. It should be noted that this is a first pass at the solution of a difficult problem. The neuron and network models chosen are related to biology but do not contain all of its complexities, some of which we hope to add to the model in future work. A variety of new results have been obtained. First, the method has been tailored to produce connection weight matrix solutions for networks with important features of biological neural (bioneural) networks. Second, a computationally efficient method of finding a robust central solution has been developed. This later method also enables us to find the most consistent solution in the presence of noisy data. Prospects of applying our method to identify bioneural network connections are exciting because such connections are almost impossible to measure in the laboratory. Knowledge of such connections would facilitate an understanding of bioneural networks and would allow the construction of the electronic counterparts of bioneural networks on very large scale integrated (VLSI) circuits.

Demuth, H.↗
NASA NTRS1996

[Vestibular compensation studies]

The following topics are reported: neurophysiological studies on MVN neurons during vestibular compensation; effects of spinal cord lesions on VNC neurons during compensation; a closed-loop vestibular compensation model for horizontally canal-related MVN neurons; spatiotemporal convergence in VNC neurons; contributions of irregularly firing vestibular afferents to linear and angular VOR's; application to flight studies; metabolic measures in vestibular neurons; immediate early gene expression following vestibular stimulation; morphological studies on primary afferents, central vestibular pathways, vestibular efferent projection to the vestibular end organs, and three-dimensional morphometry and imaging.

Perachio, Adrian A.↗
NASA NTRS1996

Gravity Sensor Plasticity in the Space Environment

The ability of the brain to learn from experience and to adapt to new environments is recognized to be profound. This ability, called 'neural plasticity,' depends directly on properties of neurons (nerve cells) that permit them to change in dimension, sprout new parts called spines, change the shape and/or size of existing parts, and to generate, alter, or delete synapses. (Synapses are communication sites between neurons.) These neuronal properties are most evident during development, when evolution guides the laying down of a general plan of the nervous system. However, once a nervous system is established, experience interacts with cellular and genetic mechanisms and the internal milieu to produce unique neuronal substrates that define each individual. The capacity for experience-related neuronal growth in the brain, as measured by the potential for synaptogenesis, is speculated to be in the trillions of synapses, but the range of increment possible for any one part of the nervous system is unknown. The question has been whether more primitive endorgans such as gravity sensors of the inner ear have a capacity for adaptive change, since this is a form of learning from experience.

Ross, Muriel D.↗
NASA NTRS1999

Formation of compact myelin is required for maturation of the axonal cytoskeleton

Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

NASA Discipline Neuroscience↗
NASA NTRS1999

Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation

Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation. Copyright 1999 Elsevier Science B.V.

NASA Discipline Neuroscience↗
NASA NTRS1995

Anti-dopamine beta-hydroxylase immunotoxin-induced sympathectomy in adult rats

Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.

NASA Discipline Regulatory Physiology↗
NASA NTRS1992

Adaptability of the oxidative capacity of motoneurons

Previous studies have demonstrated that a chronic change in neuronal activation can produce a change in soma oxidative capacity, suggesting that: (i) these 2 variables are directly related in neurons and (ii) ion pumping is an important energy requiring activity of a neuron. Most of these studies, however, have focused on reduced activation levels of sensory systems. In the present study the effect of a chronic increase or decrease in motoneuronal activity on motoneuron oxidative capacity and soma size was studied. In addition, the effect of chronic axotomy was studied as an indicator of whether cytoplasmic volume may also be related to the oxidative capacity of motoneurons. A quantitative histochemical assay for succinate dehydrogenase activity was used as a measure of motoneuron oxidative capacity in experimental models in which chronic electromyography has been used to verify neuronal activity levels. Spinal transection reduced, and spinal isolation virtually eliminated lumbar motoneuron electrical activity. Functional overload of the plantaris by removal of its major synergists was used to chronically increase neural activity of the plantaris motor pool. No change in oxidative capacity or soma size resulted from either a chronic increase or decrease in neuronal activity level. These data indicate that the chronic modulation of ionic transport and neurotransmitter turnover associated with action potentials do not induce compensatory metabolic responses in the metabolic capacity of the soma of lumbar motoneurons. Soma oxidative capacity was reduced in the axotomized motoneurons, suggesting that a combination of axoplasmic transport, intracellular biosynthesis and perhaps neurotransmitter turnover represent the major energy demands on a motoneuron. While soma oxidative capacity may be closely related to neural activity in some neural systems, e.g. visual and auditory, lumbar motoneurons appear to be much less sensitive to modulations in chronic activity levels.

NASA Discipline Musculoskeletal↗