The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Neurons in the brain communicate by short electrical pulses, the so-called action potentials or spikes. How can we understand the process of spike generation? How can we understand information transmission by neurons? What happens if thousands of neurons are coupled together in a seemingly random network? How does the network connectivity determine the activity patterns? And, vice versa, how does the spike activity influence the connectivity pattern? These questions are addressed in this 2002 introduction to spiking neurons aimed at those taking courses in computational neuroscience, theoretical biology, biophysics, or neural networks. The approach will suit students of physics, mathematics, or computer science; it will also be useful for biologists who are interested in mathematical modelling. The text is enhanced by many worked examples and illustrations. There are no mathematical prerequisites beyond what the audience would meet as undergraduates: more advanced techniques are introduced in an elementary, concrete fashion when needed.

/pdf/spiking-neuron-models-single-neurons-populations-plasticity-58gzrd6ih6.pdf

Spiking Neuron Models: Single Neurons, Populations, Plasticity

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Hebbian models of development and learning require both activity-dependent synaptic plasticity and a mechanism that induces competition between different synapses. One form of experimentally observed long-term synaptic plasticity, which we call spike-timing-dependent plasticity (STDP), depends on the relative timing of pre- and postsynaptic action potentials. In modeling studies, we find that this form of synaptic modification can automatically balance synaptic strengths to make postsynaptic firing irregular but more sensitive to presynaptic spike timing. It has been argued that neurons in vivo operate in such a balanced regime. Synapses modifiable by STDP compete for control of the timing of postsynaptic action potentials. Inputs that fire the postsynaptic neuron with short latency or that act in correlated groups are able to compete most successfully and develop strong synapses, while synapses of longer-latency or less-effective inputs are weakened.

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Competitive Hebbian learning through spike-timing-dependent synaptic plasticity

Spherical bushy cells (SBCs) of the anteroventral cochlear nucleus receive input from large excitatory auditory nerve terminals, the endbulbs of Held, and mixed glycinergic/GABAergic inhibitory inputs. The latter have sufficient potency to block action potential firing in vivo and in slice recordings. However, it is not clear how well the data from slice recordings match the inhibition in the intact brain and how it contributes to complex phenomena such as non-monotonic rate-level functions (RLF). Therefore, we determined the input-output relationship of a model SBC with simulated endbulb inputs and a dynamic inhibitory conductance constrained by recordings in brain slice preparations of hearing gerbils. Event arrival times from in vivo single-unit recordings in gerbils, where 70% of SBC showed non-monotonic RLF, were used as input for the model. Model output RLFs systematically changed from monotonic to non-monotonic shape with increasing strength of tonic inhibition. A limited range of inhibitory synaptic properties consistent with the slice data generated a good match between the model and recorded RLF. Moreover, tonic inhibition elevated the AP threshold and improved the temporal precision of output functions in a SBC model with phase-dependent input conductance. We conclude that activity-dependent, summating inhibition contributes to high temporal precision of SBC spiking by filtering out weak and poorly timed EPSCs. Moreover, inhibitory parameters determined in slice recordings provide a good estimate of inhibitory mechanisms apparently active in vivo.

/pdf/inhibitory-properties-underlying-non-monotonic-input-output-3wa65g16ih.pdf

Inhibitory properties underlying non-monotonic input-output relationship in low-frequency spherical bushy neurons of the gerbil

The middle ears of birds are typically connected by interaural cavities that form a cranial canal. Eardrums coupled in this manner may function as pressure difference receivers rather than pressure receivers. Hereby, the eardrum vibrations become inherently directional. The barn owl also has a large interaural canal, but its role in barn owl hearing and specifically in sound localization has been controversial so far. We discuss here existing data and the role of the interaural canal in this species and add a new dataset obtained by laser Doppler vibrometry in a free-field setting. Significant sound transmission across the interaural canal occurred at low frequencies. The sound transmission induces considerable eardrum directionality in a narrow band from 1.5 to 3.5 kHz. This is below the frequency range used by the barn owl for locating prey, but may conceivably be used for locating conspecific callers.

Low frequency eardrum directionality in the barn owl induced by sound transmission through the interaural canal

Extracellular field potentials (EFPs) are an important source of information in neuroscience, but their physiological basis is in many cases still a matter of debate. Axonal sources are typically discounted in modeling and data analysis because their contributions are assumed to be negligible. Here, we established experimentally and theoretically that contributions of axons to EFPs can be significant. Modeling action potentials propagating along axons, we showed that EFPs were prominent in the presence of terminal zones where axons branch and terminate in close succession, as found in many brain regions. Our models predicted a dipolar far field and a polarity reversal at the center of the terminal zone. We confirmed these predictions using EFPs from the barn owl auditory brainstem where we recorded in nucleus laminaris using a multielectrode array. These results demonstrate that axonal terminal zones can produce EFPs with considerable amplitude and spatial reach.

Dipolar extracellular potentials generated by axonal projections.

>A Highly Rudimentary Circadian Melatonin Profile in a Nocturnal Bird, the Barn Owl (Tyto alba)

The neurophonic potential is a synchronized frequency-following extracellular field potential that can be recorded in the nucleus laminaris (NL) in the brainstem of the barn owl. Putative generators of the neurophonic are the afferent axons from the nucleus magnocellularis, synapses onto NL neurons, and spikes of NL neurons. The outputs of NL, i.e., action potentials of NL neurons, are only weakly represented in the neurophonic. Instead, the inputs to NL, i.e., afferent axons and their synaptic potentials, are the predominant origin of the neurophonic (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274–2290, 2010). Thus in NL the monaural inputs from the two brain sides converge and create a binaural neurophonic. If these monaural inputs contribute independently to the extracellular field, the response to binaural stimulation can be predicted from the sum of the responses to ipsi- and contralateral stimulation. We found that a linear summation model explains the dependence of the responses on interaural time difference as measured experimentally with binaural stimulation. The fit between model predictions and data was excellent, even without taking into account the nonlinear responses of NL coincidence detector neurons, although their firing rate and synchrony strongly depend on the interaural time difference. These results are consistent with the view that the afferent axons and their synaptic potentials in NL are the primary origin of the neurophonic.

Hermann Wagner

Papers

Inhibitory properties underlying non-monotonic input-output relationship in low-frequency spherical bushy neurons of the gerbil

Low frequency eardrum directionality in the barn owl induced by sound transmission through the interaural canal

Dipolar extracellular potentials generated by axonal projections.

>A Highly Rudimentary Circadian Melatonin Profile in a Nocturnal Bird, the Barn Owl (Tyto alba)

Linear summation in the barn owl's brainstem underlies responses to interaural time differences