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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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Melatonin-Induced Modulation of Cholesterol-Enriched Model Neuronal Membranes

Melatonin, a hormone primarily produced by the brain’s pineal gland, not only regulates circadian rhythms, but also influences the structural and biophysical properties of neuronal membranes. Its amphiphilic nature enables direct incorporation into lipid bilayers and preferential interactions with cholesterol-rich lipid rafts, critical hubs for cellular signaling and membrane organization. Despite increasing recognition of its membrane activity, the molecular basis of melatonin’s interactions with coexisting liquid-ordered (L o ) and liquid-disordered (L d ) phases remains unclear. Here, in this study, we combine small-angle neutron scattering (SANS) and all-atom molecular dynamics simulations to examine model neuronal membranes composed of DSPC, DOPC, POPC, and cholesterol. Our results show that melatonin preserves domain morphology while adopting distinct orientations within the bilayer and at the membrane interface, allowing both lateral and transmembrane bridging across lipid phases. These findings establish the molecular underpinnings of melatonin’s modulation of membrane heterogeneity and provide strong support for its receptor-independent actions.

atomistic simulations↗
DOE OSTI2025

Neuronal Plasma Membranes as Supramolecular Assemblies for Biological Memory

Biological memory is the ability to develop, retain, and retrieve information over time. Currently, it is widely accepted that memories are stored in synapses (i.e., connections between brain cells throughout the brain) through a process known as synaptic plasticity, which leads to either long-term potentiation (LTP) or long-term depression (LTD). However, the strengthening (LTP) and weakening (LTD) of synapses involve post-translational modifications to neural networks requiring de novo gene expression, a lengthy and energetically expensive process. Recently, we observed that lipid bilayers in the absence of peptides/proteins are capable of LTP, not unlike what has been observed in mammals and birds. As such, this finding has prompted us to postulate that the lipid bilayer provides a good model for understanding the molecular basis of biological memory. Here, in this article, we discuss the status, challenges, and opportunities of neuronal plasma membranes as structures for biological memory and learning, therapeutic targets for various brain disorders, and platforms for neural network developments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

A Unidirectional Two-Compartment Neuron Circuit with On-chip STDP learning

Most neuromorphic chips implement the single-compartment point neuron model where synapse circuits connect directly to a leaky integrate and fire (LIF) soma circuit. However, when using a biologically plausible soma circuit (e.g., Hodgkin-Huxley neuron model), an interface circuitry, such as a current conveyor circuit, is needed to transmit synaptic current to the soma circuit. This is especially true for ultra-low power neuron circuits, where membrane capacitance is on the order of 20 fF. This need for an interface circuit arises because the parasitic capacitance and leakage current caused by fabrication mismatch and second-order effects of the output transistors in the synapse circuits can disturb the spiking dynamics of the soma circuit if connected without an interface. Using an interface circuit to isolate the soma’s membrane capacitor from synapses resolves this issue. We propose to use a unidirectional resistor (a transconductance circuit) to connect the synapse and soma circuits instead of conventional current conveyor circuits. Using a biologically plausible spike pattern detection model, we show that the on-chip spike-timing-dependent plasticity (STDP) learning performance of the proposed unidirectional two-compartment neuron circuit is similar to a single-compartment circuit (with a current conveyor as an interface) and additionally, it is more power-efficient and biologically plausible. The chip is fabricated in the Taiwan Semiconductor Manufacturing Company (TSMC) 250 nm technology node and comprises a single neuron circuit.

Gautam, Ashish [ORNL]↗
NASA NTRS1992

Choline metabolism as a basis for the selective vulnerability of cholinergic neurons

The unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.

NASA Discipline Regulatory Physiology↗
NASA NTRS1976

Effects of high-LET particles /A-40/ on the brain of Drosophila melanogaster

To investigate the effects of galactic heavy particles on nervous tissue, Drosophila melanogaster flies were exposed to A-40 from the Super-HILAC accelerator at the Lawrence Berkeley Laboratory. The energy of the particles reaching the Drosophila neurons was 4.8 MeV/nucleon, and the fluence ranged from 60,000 to 80 million particles/sq cm. Thirty-five days after irradiation at the higher fluences, extensive tissue fragmentation and cysts were found. At fluences as low as one hit/two cell bodies (about 5 million) and one hit/90 cell bodies (about 90,000 particles/sq cm or 21 rad average dose) swelling of neuronal cytoplasm and focally fragmented membranes were noted; at fluences ranging from one hit/six to one hit/135 cell bodies, there was frequently a marked increase in glial lamellae around nerve-cell processes, which often had degenerative features. These findings support the view that single hits by heavy particles may injure nervous tissue.

Miquel, J.↗
NASA NTRS1991

Biological neural networks as model systems for designing future parallel processing computers

One of the more interesting debates of the present day centers on whether human intelligence can be simulated by computer. The author works under the premise that neurons individually are not smart at all. Rather, they are physical units which are impinged upon continuously by other matter that influences the direction of voltage shifts across the units membranes. It is only the action of a great many neurons, billions in the case of the human nervous system, that intelligent behavior emerges. What is required to understand even the simplest neural system is painstaking analysis, bit by bit, of the architecture and the physiological functioning of its various parts. The biological neural network studied, the vestibular utricular and saccular maculas of the inner ear, are among the most simple of the mammalian neural networks to understand and model. While there is still a long way to go to understand even this most simple neural network in sufficient detail for extrapolation to computers and robots, a start was made. Moreover, the insights obtained and the technologies developed help advance the understanding of the more complex neural networks that underlie human intelligence.

Ross, Muriel D.↗
NASA NTRS1992

Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro

We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

Non-NASA Center↗
NASA NTRS1993

The reducing agent dithiothreitol (DTT) does not abolish the inhibitory nicotinic response recorded from rat dorsolateral septal neurons

Previous intracellular recordings have demonstrated that dorsolateral septal nucleus (DLSN) neurons express a novel nicotinic receptor which produces a direct membrane hyperpolarization when activated by nicotinic agonists. Activation of the classical excitatory nicotinic receptors has been shown to require a disulfide bond involving the cysteines at positions 192 and 193 of the alpha subunits of the receptor. Reduction of this cystine bond with dithiothreitol (DTT) abolishes agonist activation of excitatory nicotinic receptors. We have now examined whether DTT treatment of the inhibitory nicotinic receptor on DLSN neurons also abolishes the inhibitory nicotinic response. We find that the inhibitory response persists after treatment of the neurons with 1 mM DTT, even if the reduction is followed by alkylation of the receptor with bromoacetylcholine to prevent possible reformation of disulfide bonds. This result suggests that the agonist binding site on the inhibitory nicotinic receptor does not require an intact disulfide bond, similar to the bond on the alpha subunit of the excitatory nicotinic receptor, for agonist activation of the receptor. Some of these results have been previously reported in abstract form.

NASA Discipline Number 16-10↗
NASA NTRS1992

Electrophysiology of the mammillary complex in vitro. I. Tuberomammillary and lateral mammillary neurons

1. The electrophysiological properties of the tuberomammillary and lateral mammillary neurons in the guinea pig mammillary body were studied using an in vitro brain slice preparation. 2. Tuberomammillary (n = 79) neurons were recorded mainly ventral to the lateral mammillary body as well as ventromedially to the fornix within the rostral part of the medial mammillary nucleus. Intracellular staining with horseradish peroxidase (n = 9) and Lucifer yellow (n = 3) revealed that these cells have several thick, long, spiny dendrites emerging from large (20-35 microns) fusiform somata. 3. Most tuberomammillary neurons (66%) fired spontaneously at a relatively low frequency (0.5-10 Hz) at the resting membrane potential. The action potentials were broad (2.3 ms) with a prominent Ca(2+)-dependent shoulder on the falling phase. Deep (17.8 mV), long-lasting spike afterhyperpolarizations were largely Ca(2+)-independent. 4. All tuberomammillary neurons recorded displayed pronounced delayed firing when the cells were activated from a potential negative to the resting level. The cells also displayed a delayed return to the baseline at the break of hyperpolarizing pulses applied from a membrane potential level close to firing threshold. Analysis of the voltage- and time dependence of this delayed rectification suggested the presence of a transient outward current similar to the A current (IA). These were not completely blocked by high concentrations of 4-aminopyridine, whereas the delayed onset of firing was always abolished when voltage-dependent Ca2+ conductances were blocked by superfusion with Cd2+. 5. Tuberomammillary neurons also displayed inward rectification in the hyperpolarizing and, primarily, depolarizing range. Block of voltage-gated Na(+)-dependent conductances with tetrodotoxin (TTX) selectively abolished inward rectification in the depolarizing range, indicating the presence of a persistent low-threshold sodium-dependent conductance (gNap). In fact, persistent TTX-sensitive, plateau potentials were always elicited following Ca2+ block with Cd2+ when K+ currents were reduced by superfusion with tetraethylammonium. 6. The gNap in tuberomammillary neurons may subserve the pacemaker current underlying the spontaneous firing of these cells. The large-amplitude spike afterhyperpolarization of these neurons sets the availability of the transient outward rectifier, which, in conjunction with the pacemaker current, establishes the rate at which membrane potential approaches spike threshold. 7. Repetitive firing elicited by direct depolarization enhanced the spike shoulder of tuberomammillary neurons. Spike trains were followed by a Ca(2+)-dependent, apamine-sensitive, slow afterhyperpolarization. 8. Lateral mammillary neurons were morphologically and electrophysiologically different from tuberomammillary neurons. All lateral mammillary neurons neurons recorded (n = 44) were silent at rest (-60 mV).(ABSTRACT TRUNCATED AT 400 WORDS).

Non-NASA Center↗
DOE OSTI2025

Composite Behavior of Nanopore Array Large Memristors

Synthetic nanopores were recently demonstrated with memristive and nonlinear voltage-current behaviors, akin to ion channels in a cell membrane. Such ionic devices are considered a promising candidate for the development of brain-inspired neuromorphic computing techniques. In this work, we show the composite behavior of nanopore-array large memristors, formed with different membrane materials, pore sizes, electrolytes, and device arrangements. Anodic aluminum oxide (AAO) membranes with 5 nm and 20 nm diameter pores and track-etched polycarbonate (PCTE) membranes with 10 nm diameter pores are tested and shown to demonstrate memristive and nonlinear behaviors with approximately 107–1010 pores in parallel when electrolyte concentration across the membranes is asymmetric. Ion diffusion through the large number of channels induces time-dependent electrolyte asymmetry that drives the system through different memristive states. The behaviors of series composite memristors with different configurations are also presented. In addition to helping understand fluidic devices and circuits for neuromorphic computing, the results also shed light on the development of field-assisted ion-selection-membrane filtration techniques as well as the investigations of large neurons and giant synapses. Further work is needed to de-embed parasitic components of the measurement setup to obtain intrinsic large memristor properties.

Chemistry↗
NASA NTRS1992

Electrophysiology of the mammillary complex in vitro. II. Medial mammillary neurons

1. The electrophysiological properties of guinea pig medial mammillary body (MMB) neurons were studied using an in vitro slice preparation. 2. The neurons (n = 80) had an average resting potential of -57 +/- 5.5 (SD) mV, an input resistance of 176 +/- 83 M omega, and a spike amplitude of 58 +/- 15.7 mV. Most of the neurons were silent at rest (n = 52), but some fired spontaneous single spikes (n = 16) or spike bursts (n = 14). 3. The main electrophysiological characteristic of MMB neurons was the ability to generate Ca(2+)-dependent regenerative events, which resulted in very robust burst responses. However, this regenerative event was not the same for all neurons, ranging from typical low-threshold Ca2+ spikes (LTSs) to intermediate-threshold plateau potentials (ITPs). 4. The ITPs were distinct from the LTSs in that they lasted > or = 100 ms and were not inactivated at membrane potentials at or positive to -55 mV. 5. Some cells with a prominent ITP and no LTS (n = 36) displayed repetitive, usually rhythmic, bursting (n = 14). This ITP could be powerful enough to maintain rhythmic membrane potential oscillations after pharmacological block of Na+ conductances. 6. A group of 32 MMB neurons displayed complex bursting that was generated by activation of both LTSs and ITPs. This was established on the basis of their distinct time- and voltage-dependent characteristics. In a group of neurons (n = 14), the burst responses were exclusively generated by an LTS; however, a Ca(2+)-dependent plateau potential contributed to the generation of rebound-triggered oscillatory firing. 7. In addition to the Ca(2+)-dependent LTS and/or ITP, MMB neurons always displayed high-threshold Ca2+ spikes after reduction of K+ conductances with tetraethylammonium. 8. MMB neurons display one of the richer varieties of voltage-dependent Ca2+ conductances so far encountered in mammalian CNS. We propose that the very prominent endogenous bursting and oscillatory properties of MB neurons allow this nuclear complex to function as an oscillatory relay for the transmission of low-frequency rhythmic activities throughout the limbic circuit.

NASA Discipline Neuroscience↗
NASA NTRS1992

Metabotropic glutamate receptor agonists potentiate a slow afterdepolarization in CNS neurons

We have previously reported that, in the rat dorsolateral septal nucleus (DLSN), metabotropic glutamate receptor (met-GluR) agonists evoked a slow depolarization accompanied by an increase in membrane conductance and burst firing. We have speculated that the burst firing elicited by met-GluR agonists may be due to activation or enhancement of a non-specific cation current, which exists in some DLSN neurons. Now we report that a slow afterdepolarization (sADP) mediated by a non-specific cation current was potentiated by both 1S,3R-ACPD and quisqualate. In addition, met-GluR agonists unmask a sADP in DLSN neurons which did not show a sADP under control conditions. Our data suggest that a non-specific cation current can be potentiated by activation of the met-GluR.

Non-NASA Center↗
DOE OSTI2025

Dense, continuous membrane labeling and expansion microscopy visualization of ultrastructure in tissues

Abstract Lipid membranes are key to the nanoscale compartmentalization of biological systems, but fluorescent visualization of them in intact tissues, with nanoscale precision, is challenging to do with high labeling density. Here, we report ultrastructural membrane expansion microscopy (umExM), which combines an innovative membrane label and optimized expansion microscopy protocol, to support dense labeling of membranes in tissues for nanoscale visualization. We validate the high signal-to-background ratio, and uniformity and continuity, of umExM membrane labeling in brain slices, which supports the imaging of membranes and proteins at a resolution of ~60 nm on a confocal microscope. We demonstrate the utility of umExM for the segmentation and tracing of neuronal processes, such as axons, in mouse brain tissue. Combining umExM with optical fluctuation imaging, or iterating the expansion process, yields ~35 nm resolution imaging, pointing towards the potential for electron microscopy resolution visualization of brain membranes on ordinary light microscopes.

Science & Technology - Other Topics↗
NASA NTRS1974

Fine structural changes in the lateral vestibular nucleus of aging rats

The fine structure of the lateral vestibular nucleus was investigated in Sprague-Dawley rats, that were sacrified at 4 weeks, 6-8 weeks, 6-8 months, and 18-20 months of age. In the neuronal perikaria, the following age-associated changes were seen with increasing frequency with advancing age: rodlike nuclear inclusions and nuclear membrane invaginations; cytoplasmic dense bodies with the characteristics of lipofuscin; and moderate disorganization of the granular endoplasmic reticulum. Dense bodies were also seen in glial cells. Rats 18 to 20 months old showed dendritic swellings, axonal degeneration, and an apparent increase in the number of axosomatic synaptic terminals containing flattened vesicles (presumed to be inhibitory in function).

Johnson, J. E., Jr.↗
NASA NTRS1982

Effect of limb immobilization on skeletal muscle

Current knowledge and questions remaining concerning the effects of limb immobilization on skeletal muscle is reviewed. The most dramatic of these effects is muscle atrophy, which has been noted in cases of muscles fixed at or below their resting length. Immobilization is also accompanied by a substantial decrease in motoneuronal discharges, which results in the conversion of slow-twitch muscle to muscle with fast-twitch characteristics. Sarcolemma effects include no change or a decrease in resting membrane potential, the appearance of extrajunctional acetylcholine receptors, and no change in acetylcholinesterase activity. Evidence of changes in motoneuron after hyperpolarization characteristics suggests that the muscle inactivity is responsible for neuronal changes, rather than vice versa. The rate of protein loss from atrophying muscles is determined solely by the first-order rate constant for degradation. Various other biochemical and functional changes have been noted, including decreased insulin responsiveness and protein synthesis. The model of limb immobilization may also be useful for related studies of muscle adaptation.

Booth, F. W.↗