Axonal Activity In Vivo: Technical Considerations and Implications for the Exploration of Neural Circuits in Freely Moving Animals

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We have recently reported extracellular tetrode recordings of short duration waveforms (SDWs) with an average peak-trough duration less than 172μs. These waveforms have significantly shorter duration than somatic action potentials and tend to be triphasic. The present review discusses further data that suggests SDWs are representative of axonal activity, how this characterization allows for more accurate classification of somatic activity and could serve as a means of exploring signal integration in neural circuits. The review also discusses how axons may function as more than neural cables and the implications this may have for axonal information processing. While the technical challenges necessary for the exploration of axonal processes in functional neural circuits during behavior are impressive, preliminary evidence suggests that the in vivo study of axons is attainable. The resulting theoretical implications for systems level function make refinement of this approach a necessary goal toward developing a more complete understanding of the processes underlying learning, memory and attention as well as the pathological states underlying mental illness and epilepsy

Short Duration Waveforms Recorded Extracellularly from Freely Moving Rats are Representative of Axonal Activity

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation along axons. We describe SDWs recorded from pure white-matter tracts including the alveus and corpus callosum. Recordings of several SDWs in the alveus exhibit grid-like firing patterns suggesting these axons carry spatial information from entorhinal cortical neurons. Finally, we locally injected the GABAA agonist Muscimol into layer CA1 of the hippocampus while simultaneously recording somatic activity and SDWs on the same tetrodes. The persistent activity of SDWs during Muscimol inactivation of somatic action potentials indicates that SDWs are representative of action potential propagation along axons projecting from more distal somata. This characterization is important as it illustrates the dangers of exclusively using spike duration as the sole determinant of unit type, particularly in the case of interneurons whose peak-trough times overlap with SDWs. It may also allow future studies to explore how axonal projections from disparate brain regions integrate spatial information in the hippocampus, and provide a basis for studying the effects of pharmaceutical agents on signal transmission in axons, and ultimately to aid in defining the potential role of axons in cognition

Enrichment and Training Improve Cognition in Rats with Cortical Malformations

Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group of control and MAM rats without enrichment were trained until they reached criterion on the place avoidance task. MAM rats had impaired performance on spatial tasks and enrichment improved performance of both control and MAM animals. Although MAM rats did not have a deficit in sociability they showed similar improvement with enrichment as controls. MRI revealed a whole brain volume decrease with MAM exposure, and an increase in both MAM and control enriched volumes in comparison to non-enriched animals. In the place avoidance task, MAM rats required approximately 3 times as long to reach criterion as control animals, but with additional training were able to reach control performance. Environmental manipulation and additional training can improve cognition in a rodent MCD model. We therefore suggest that patients with MCD may benefit from appropriate alterations in educational strategies, social interaction and environment. These factors should be considered in therapeutic strategies

The HST Key Project on the Extragalactic Distance Scale XXV. A Recalibration of Cepheid Distances to Type Ia Supernovae and the Value of the Hubble Constant

Cepheid-based distances to seven Type Ia supernovae (SNe)-host galaxies have been derived using the standard HST Key Project on the Extragalactic Distance Scale pipeline. For the first time, this allows for a transparent comparison of data accumulated as part of three different HST projects, the Key Project, the Sandage et al. Type Ia SNe program, and the Tanvir et al. Leo I Group study. Re-analyzing the Tanvir et al. galaxy and six Sandage et al. galaxies we find a mean (weighted) offset in true distance moduli of 0.12+/-0.07 mag -- i.e., 6% in linear distance -- in the sense of reducing the distance scale, or increasing H0. Adopting the reddening-corrected Hubble relations of Suntzeff et al. (1999), tied to a zero point based upon SNe~1990N, 1981B, 1998bu, 1989B, 1972E and 1960F and the photometric calibration of Hill et al. (1998), leads to a Hubble constant of H0=68+/-2(random)+/-5(systematic) km/s/Mpc. Adopting the Kennicutt et al. (1998) Cepheid period-luminosity-metallicity dependency decreases the inferred H0 by 4%. The H0 result from Type Ia SNe is now in good agreement, to within their respective uncertainties, with that from the Tully-Fisher and surface brightness fluctuation relations.Comment: Accepted for publication in The Astrophysical Journal. 62 pages, LaTeX, 9 Postscript figures. Also available at http://casa.colorado.edu/~bgibson/publications.htm

The HST Key Project on the Extragalactic Distance Scale. XXVIII. Combining the Constraints on the Hubble Constant

Since the launch of the Hubble Space Telescope nine years ago, Cepheid distances to 25 galaxies have been determined for the purpose of calibrating secondary distance indicators. A variety of these can now be calibrated, and the accompanying papers by Sakai, Kelson, Ferrarese, and Gibson employ the full set of 25 galaxies to consider the Tully-Fisher relation, the fundamental plane of elliptical galaxies, Type Ia supernovae, and surface brightness fluctuations. When calibrated with Cepheid distances, each of these methods yields a measurement of the Hubble constant and a corresponding measurement uncertainty. We combine these measurements in this paper, together with a model of the velocity field, to yield the best available estimate of the value of H_0 within the range of these secondary distance indicators and its uncertainty. The result is H_0 = 71 +/- 6 km/sec/Mpc. The largest contributor to the uncertainty of this 67% confidence level result is the distance of the Large Magellanic Cloud, which has been assumed to be 50 +/- 3 kpc

A Database of Cepheid Distance Moduli and TRGB, GCLF, PNLF and SBF Data Useful for Distance Determinations

We present a compilation of Cepheid distance moduli and data for four secondary distance indicators that employ stars in the old stellar populations: the planetary nebula luminosity function (PNLF), the globular cluster luminosity function (GCLF), the tip of the red giant branch (TRGB), and the surface brightness fluctuation (SBF) method. The database includes all data published as of July 15, 1999. The main strength of this compilation resides in all data being on a consistent and homogeneous system: all Cepheid distances are derived using the same calibration of the period-luminosity relation, the treatment of errors is consistent for all indicators, measurements which are not considered reliable are excluded. As such, the database is ideal for inter-comparing any of the distance indicators considered, or for deriving a Cepheid calibration to any secondary distance indicator. Specifically, the database includes: 1) Cepheid distances, extinctions and metallicities; 2) apparent magnitudes of the PNLF cutoff; 3) apparent magnitudes and colors of the turnover of the GCLF (both in the V- and B-bands); 4) apparent magnitudes of the TRGB (in the I-band) and V-I colors at and 0.5 magnitudes fainter than the TRGB; 5) apparent surface brightness fluctuation magnitudes I, K', K_short, and using the F814W filter with the HST/WFPC2. In addition, for every galaxy in the database we give reddening estimates from DIRBE/IRAS as well as HI maps, J2000 coordinates, Hubble and T-type morphological classification, apparent total magnitude in B, and systemic velocity. (Abridged)Comment: Accepted for publication in the Astrophysical Journal Supplement Series. Because of space limitations, the figures included are low resolution bitmap images. Original figures can be found at http://www.astro.ucla.edu/~laura/pub.ht

Care that Matters: Quality Measurement and Health Care

Barry Saver and colleagues caution against the use of process and performance metrics as health care quality measures in the United States

Multiple origins, one evolutionary trajectory: gradual evolution characterizes distinct lineages of allotetraploid "Brachypodium"

The “genomic shock” hypothesis posits that unusual challenges to genome integrity such as whole genome duplication may induce chaotic genome restructuring. Decades of research on polyploid genomes have revealed that this is often, but not always the case. While some polyploids show major chromosomal rearrangements and derepression of transposable elements in the immediate aftermath of whole genome duplication, others do not. Nonetheless, all polyploids show gradual diploidization over evolutionary time. To evaluate these hypotheses, we produced a chromosome-scale reference genome for the natural allotetraploid grass Brachypodium hybridum, accession “Bhyb26.” We compared 2 independently derived accessions of B. hybridum and their deeply diverged diploid progenitor species Brachypodium stacei and Brachypodium distachyon. The 2 B. hybridum lineages provide a natural timecourse in genome evolution because one formed 1.4 million years ago, and the other formed 140 thousand years ago. The genome of the older lineage reveals signs of gradual post-whole genome duplication genome evolution including minor gene loss and genome rearrangement that are missing from the younger lineage. In neither B. hybridum lineage do we find signs of homeologous recombination or pronounced transposable element activation, though we find evidence supporting steady post-whole genome duplication transposable element activity in the older lineage. Gene loss in the older lineage was slightly biased toward 1 subgenome, but genome dominance was not observed at the transcriptomic level. We propose that relaxed selection, rather than an abrupt genomic shock, drives evolutionary novelty in B. hybridum, and that the progenitor species’ similarity in transposable element load may account for the subtlety of the observed genome dominance