Very short-term plasticity in hippocampal synapses

Hippocampal pyramidal neurons often fire in bursts of action potentials with short interspike intervals (2–10 msec). These high-frequency bursts may play a critical role in the functional behavior of hippocampal neurons, but synaptic plasticity at such short times has not been carefully studied. To study synaptic modulation at very short time intervals, we applied pairs of stimuli with interpulse intervals ranging from 7 to 50 msec to CA1 synapses isolated by the method of minimal stimulation in hippocampal slices. We have identified three components of short-term paired-pulse modulation, including (i) a form of synaptic depression manifested after a prior exocytotic event, (ii) a form of synaptic depression that does not depend on a prior exocytotic event and that we postulate is based on inactivation of presynaptic N-type Ca2+ channels, and (iii) a dependence of paired-pulse facilitation on the exocytotic history of the synapse.

The resource consumption principle: attention and memory in volumes of neural tissue.

In the cerebral cortex, the small volume of the extracellular space in relation to the volume enclosed by synapses suggests an important functional role for this relationship. It is well known that there are atoms and molecules in the extracellular space that are absolutely necessary for synapses to function (e.g., calcium). I propose here the hypothesis that the rapid shift of these atoms and molecules from extracellular to intrasynaptic compartments represents the consumption of a shared, limited resource available to local volumes of neural tissue. Such consumption results in a dramatic competition among synapses for resources necessary for their function. In this paper, I explore a theory in which this resource consumption plays a critical role in the way local volumes of neural tissue operate. On short time scales, this principle of resource consumption permits a tissue volume to choose those synapses that function in a particular context and thereby helps to integrate the many neural signals that impinge on a tissue volume at any given moment. On longer time scales, the same principle aids in the stable storage and recall of information. The theory provides one framework for understanding how cerebral cortical tissue volumes integrate, attend to, store, and recall information. In this account, the capacity of neural tissue to attend to stimuli is intimately tied to the way tissue volumes are organized at fine spatial scales.

Rapid local synchronization of action potentials: toward computation with coupled integrate-and-fire neurons.

The collective behavior of interconnected spiking nerve cells is investigated. It is shown that a variety of model systems exhibit the same short-time behavior and rapidly converge to (approximately) periodic firing patterns with locally synchronized action potentials. The dynamics of one model can be described by a downhill motion on an abstract energy landscape. Since an energy landscape makes it possible to understand and program computation done by an attractor network, the results will extend our understanding of collective computation from models based on a firing-rate description to biologically more realistic systems with integrate-and-fire neurons.

The old problems of glass and the glass transition, and the many new twists.

In this paper I review the ways in which the glassy state is obtained both in nature and in materials science and highlight a "new twist"--the recent recognition of polymorphism within the glassy state. The formation of glass by continuous cooling (viscous slowdown) is then examined, the strong/fragile liquids classification is reviewed, and a new twist-the possibility that the slowdown is a result of an avoided critical point-is noted. The three canonical characteristics of relaxing liquids are correlated through the fragility. As a further new twist, the conversion of strong liquids to fragile liquids by pressure-induced coordination number increases is demonstrated. It is then shown that, for comparable systems, it is possible to have the same conversion accomplished via a first-order transition within the liquid state during quenching. This occurs in the systems in which "polyamorphism" (polymorphism in the glassy state) is observed, and the whole phenomenology is accounted for by Poole's bond-modified van der Waals model. The sudden loss of some liquid degrees of freedom through such weak first-order transitions is then related to the polyamorphic transition between native and denatured hydrated proteins, since the latter are also glass-forming systems--water-plasticized, hydrogen bond-cross-linked chain polymers (and single molecule glass formers). The circle is closed with a final new twist by noting that a short time scale phenomenon much studied by protein physicists-namely, the onset of a sharp change in d/dT ( is the Debye-Waller factor)--is general for glass-forming liquids, including computer-simulated strong and fragile ionic liquids, and is closely correlated with the experimental glass transition temperature. The latter thus originates in strong anharmonicity in certain components of the vibrational density of states, which permits the system to access the multiple minima of its configuration space. The connection between the anharmonicity in these modes, vibrational localization, the Kauzmann temperature, and the fragility of the liquid is proposed as the key problem in glass science.

Free recombination within Helicobacter pylori

Sequences of three gene fragments (flaA, flaB, and vacA) from Helicobacter pylori strains isolated from patients in Germany, Canada, and South Africa were analyzed for diversity and for linkage equilibrium by using the Homoplasy Test and compatibility matrices. Horizontal genetic exchange in H. pylori is so frequent that different loci and polymorphisms within each locus are all at linkage equilibrium. These results indicate that H. pylori is panmictic. Comparisons with sequences from Escherichia coli, Neisseria meningitidis, and Drosophila melanogaster showed that recombination in H. pylori was much more frequent than in other species. In contrast, when multiple family members infected with H. pylori were investigated, some strains were indistinguishable at all three loci. Thus, H. pylori is clonal over short time periods after natural transmission.

Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms

We present a multichannel tomographic technique to detect fluorescent objects embedded in thick (6.4 cm) tissue-like turbid media using early-arriving photons. The experiments use picosecond laser pulses and a streak camera with single photon counting capability to provide short time resolution and high signal-to-noise ratio. The tomographic algorithm is based on the Laplace transform of an analytical diffusion approximation of the photon migration process and provides excellent agreement between the actual positions of the fluorescent objects and the experimental estimates. Submillimeter localization accuracy and 4- to 5-mm resolution are demonstrated. Moreover, objects can be accurately localized when fluorescence background is present. The results show the feasibility of using early-arriving photons to image fluorescent objects embedded in a turbid medium and its potential in clinical applications such as breast tumor detection.

Site-specific conformational determination in thermal unfolding studies of helical peptides using vibrational circular dichroism with isotopic substitution

Understanding the detailed mechanism of protein folding requires dynamic, site-specific stereochemical information. The short time response of vibrational spectroscopies allows evaluation of the distribution of populations in rapid equilibrium as the peptide unfolds. Spectral shifts associated with isotopic labels along with local stereochemical sensitivity of vibrational circular dichroism (VCD) allow determination of the segment sequence of unfolding. For a series of alanine-rich peptides that form α-helices in aqueous solution, we used isotopic labeling and VCD to demonstrate that the α-helix noncooperatively unwinds from the ends with increasing temperature. For these blocked peptides, the C-terminal is frayed at 5°C. Ab initio level theoretical simulations of the IR and VCD band shapes are used to analyze the spectra and to confirm the conformation of the labeled components. The VCD signals associated with the labeled residues are amplified by coupling to the nonlabeled parts of the molecule. Thus small labeled segments are detectable and stereochemically defined in moderately large peptides in this report of site-specific peptide VCD conformational analysis.

Seeing properties of an invisible object: Feature inheritance and shine-through

We characterize a class of spatio-temporal illusions with two complementary properties. Firstly, if a vernier stimulus is flashed for a short time on a monitor and is followed immediately by a grating, the latter can express features of the vernier, such as its offset, its orientation, or its motion (feature inheritance). Yet the vernier stimulus itself remains perceptually invisible. Secondly, the vernier can be rendered visible by presenting gratings with a larger number of elements (shine-through). Under these conditions, subjects perceive two independent “objects” each carrying their own features. Transition between these two domains can be effected by subtle changes in the spatio-temporal layout of the grating. This should allow psychophysicists and electrophysiologists to investigate feature binding in a precise and quantitative manner.

A molecular analysis of dietary diversity for three archaic Native Americans

DNA was extracted from three fecal samples, more than 2,000 years old, from Hinds Cave, Texas. Amplification of human mtDNA sequences showed their affiliation with contemporary Native Americans, while sequences from pronghorn antelope, bighorn sheep, and cottontail rabbit allowed these animals to be identified as part of the diet of these individuals. Furthermore, amplification of chloroplast DNA sequences identified eight different plants as dietary elements. These archaic humans consumed 2–4 different animal species and 4–8 different plant species during a short time period. The success rate for retrieval of DNA from paleofeces is in strong contrast to that from skeletal remains where the success rate is generally low. Thus, human paleofecal remains represent a source of ancient DNA that significantly complements and may in some cases be superior to that from skeletal tissue.

Electron tunneling in protein crystals

The current understanding of electron tunneling through proteins has come from work on systems where donors and acceptors are held at fixed distances and orientations. The factors that control electron flow between proteins are less well understood, owing to uncertainties in the relative orientations and structures of the reactants during the very short time that tunneling occurs. As we report here, the way around such structural ambiguity is to examine oxidation–reduction reactions in protein crystals. Accordingly, we have measured and analyzed the kinetics of electron transfer between native and Zn-substituted tuna cytochrome c (cyt c) molecules in crystals of known structure. Electron transfer rates [(320 s−1 for *Zn-cyt c → Fe(III)-cyt c; 2000 s−1 for Fe(II)-cyt c → Zn-cyt c+)] over a Zn–Fe distance of 24.1 Å closely match those for intraprotein electron tunneling over similar donor–acceptor separations. Our results indicate that van der Waals interactions and water-mediated hydrogen bonds are effective coupling elements for tunneling across a protein–protein interface.

Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis

The genetic variability at six polymorphic loci was examined within a global collection of 502 isolates of subgroup III, serogroup A Neisseria meningitidis. Nine “genoclouds” were identified, consisting of genotypes that were isolated repeatedly plus 48 descendent genotypes that were isolated rarely. These genoclouds have caused three pandemic waves of disease since the mid-1960s, the most recent of which was imported from East Asia to Europe and Africa in the mid-1990s. Many of the genotypes are escape variants, resulting from positive selection that we attribute to herd immunity. Despite positive selection, most escape variants are less fit than their parents and are lost because of competition and bottlenecks during spread from country to country. Competition between fit genotypes results in dramatic changes in population composition over short time periods.

Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus

The anatomical and biophysical specializations of octopus cells allow them to detect the coincident firing of groups of auditory nerve fibers and to convey the precise timing of that coincidence to their targets. Octopus cells occupy a sharply defined region of the most caudal and dorsal part of the mammalian ventral cochlear nucleus. The dendrites of octopus cells cross the bundle of auditory nerve fibers just proximal to where the fibers leave the ventral and enter the dorsal cochlear nucleus, each octopus cell spanning about one-third of the tonotopic array. Octopus cells are excited by auditory nerve fibers through the activation of rapid, calcium-permeable, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors. Synaptic responses are shaped by the unusual biophysical characteristics of octopus cells. Octopus cells have very low input resistances (about 7 MΩ), and short time constants (about 200 μsec) as a consequence of the activation at rest of a hyperpolarization-activated mixed-cation conductance and a low-threshold, depolarization-activated potassium conductance. The low input resistance causes rapid synaptic currents to generate rapid and small synaptic potentials. Summation of small synaptic potentials from many fibers is required to bring an octopus cell to threshold. Not only does the low input resistance make individual excitatory postsynaptic potentials brief so that they must be generated within 1 msec to sum but also the voltage-sensitive conductances of octopus cells prevent firing if the activation of auditory nerve inputs is not sufficiently synchronous and depolarization is not sufficiently rapid. In vivo in cats, octopus cells can fire rapidly and respond with exceptionally well-timed action potentials to periodic, broadband sounds such as clicks. Thus both the anatomical specializations and the biophysical specializations make octopus cells detectors of the coincident firing of their auditory nerve fiber inputs.

Initiation process of earthquakes and its implications for seismic hazard reduction strategy.

For the average citizen and the public, "earthquake prediction" means "short-term prediction," a prediction of a specific earthquake on a relatively short time scale. Such prediction must specify the time, place, and magnitude of the earthquake in question with sufficiently high reliability. For this type of prediction, one must rely on some short-term precursors. Examinations of strain changes just before large earthquakes suggest that consistent detection of such precursory strain changes cannot be expected. Other precursory phenomena such as foreshocks and nonseismological anomalies do not occur consistently either. Thus, reliable short-term prediction would be very difficult. Although short-term predictions with large uncertainties could be useful for some areas if their social and economic environments can tolerate false alarms, such predictions would be impractical for most modern industrialized cities. A strategy for effective seismic hazard reduction is to take full advantage of the recent technical advancements in seismology, computers, and communication. In highly industrialized communities, rapid earthquake information is critically important for emergency services agencies, utilities, communications, financial companies, and media to make quick reports and damage estimates and to determine where emergency response is most needed. Long-term forecast, or prognosis, of earthquakes is important for development of realistic building codes, retrofitting existing structures, and land-use planning, but the distinction between short-term and long-term predictions needs to be clearly communicated to the public to avoid misunderstanding.