Slowness: an objective for spike-timing-dependent plasticity?

Our nervous system can efficiently recognize objects in spite of changes in contextual variables such as perspective or lighting conditions. Several lines of research have proposed that this ability for invariant recognition is learned by exploiting the fact that object identities typically vary more slowly in time than contextual variables or noise. Here, we study the question of how this "temporal stability" or "slowness" approach can be implemented within the limits of biologically realistic spike-based learning rules. We first show that slow feature analysis, an algorithm that is based on slowness, can be implemented in linear continuous model neurons by means of a modified Hebbian learning rule. This approach provides a link to the trace rule, which is another implementation of slowness learning. Then, we show analytically that for linear Poisson neurons, slowness learning can be implemented by spike-timing-dependent plasticity (STDP) with a specific learning window. By studying the learning dynamics of STDP, we show that for functional interpretations of STDP, it is not the learning window alone that is relevant but rather the convolution of the learning window with the postsynaptic potential. We then derive STDP learning windows that implement slow feature analysis and the "trace rule." The resulting learning windows are compatible with physiological data both in shape and timescale. Moreover, our analysis shows that the learning window can be split into two functionally different components that are sensitive to reversible and irreversible aspects of the input statistics, respectively. The theory indicates that irreversible input statistics are not in favor of stable weight distributions but may generate oscillatory weight dynamics. Our analysis offers a novel interpretation for the functional role of STDP in physiological neurons.     

The role of the fluid phase in the viscous response of bovine periodontal ligament

The mechanical response of the periodontal ligament (PDL) is complex. This tissue responds as a hyperelastic solid when pulled in tension while demonstrating a viscous behavior under compression. This intricacy is reflected in the tissue's morphology, which comprises fibers, glycosaminoglycans, a jagged interface with the surrounding porous bone and an extensive vascular network.In the present study we offer an analysis of the viscous behavior and the interplay between the fibrous matrix and its fluid phase.Cylindrical specimens comprising layers of dentine, PDL and bone were extracted from bovine first molars and affixed to a tensile-compressive loading machine. The viscous properties of the tissue were analyzed (1) by subjecting the specimens to sinusoidal displacements at various frequencies and (2) by cycling the specimens in ‘fully saturated’ and in ‘partially dry’ conditions. Both modes assisted in determining the contribution of the fluid phase to the mechanical response.It was concluded that: (1) PDL showed pseudo-plastic viscous features for cyclic compressive loading, (2) these viscous features essentially resulted from interactions between the porous matrix and unbound fluid content of the tissue. Removing the liquid from the PDL largely eliminates its damping effect in compression.     

Memory Storage Fidelity in the Hippocampal Circuit: The Role of Subregions and Input Statistics

In the last decades a standard model regarding the function of the hippocampus in memory formation has been established and tested computationally. It has been argued that the CA3 region works as an auto-associative memory and that its recurrent fibers are the actual storing place of the memories. Furthermore, to work properly CA3 requires memory patterns that are mutually uncorrelated. It has been suggested that the dentate gyrus orthogonalizes the patterns before storage, a process known as pattern separation. In this study we review the model when random input patterns are presented for storage and investigate whether it is capable of storing patterns of more realistic entorhinal grid cell input. Surprisingly, we find that an auto-associative CA3 net is redundant for random inputs up to moderate noise levels and is only beneficial at high noise levels. When grid cell input is presented, auto-association is even harmful for memory performance at all levels. Furthermore, we find that Hebbian learning in the dentate gyrus does not support its function as a pattern separator. These findings challenge the standard framework and support an alternative view where the simpler EC-CA1-EC network is sufficient for memory storage.     

The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input

Recently, we presented a study of adult neurogenesis in a simplified hippocampal memory model. The network was required to encode and decode memory patterns despite changing input statistics. We showed that additive neurogenesis was a more effective adaptation strategy compared to neuronal turnover and conventional synaptic plasticity as it allowed the network to respond to changes in the input statistics while preserving representations of earlier environments. Here we extend our model to include realistic, spatially driven input firing patterns in the form of grid cells in the entorhinal cortex. We compare network performance across a sequence of spatial environments using three distinct adaptation strategies: conventional synaptic plasticity, where the network is of fixed size but the connectivity is plastic; neuronal turnover, where the network is of fixed size but units in the network may die and be replaced; and additive neurogenesis, where the network starts out with fewer initial units but grows over time. We confirm that additive neurogenesis is a superior adaptation strategy when using realistic, spatially structured input patterns. We then show that a more biologically plausible neurogenesis rule that incorporates cell death and enhanced plasticity of new granule cells has an overall performance significantly better than any one of the three individual strategies operating alone. This adaptation rule can be tailored to maximise performance of the network when operating as either a short- or long-term memory store. We also examine the time course of adult neurogenesis over the lifetime of an animal raised under different hypothetical rearing conditions. These growth profiles have several distinct features that form a theoretical prediction that could be tested experimentally. Finally, we show that place cells can emerge and refine in a realistic manner in our model as a direct result of the sparsification performed by the dentate gyrus layer.     

Macrophages are the major reservoir of latent murine gammaherpesvirus 68 in peritoneal cells

B cells have previously been identified as the major hematopoietic cell type harboring latent gammaherpesvirus 68 (gammaHV68) (N. P. Sunil-Chandra, S. Efstathiou, and A. A. Nash, J. Gen. Virol. 73:3275-3279, 1992). However, we have shown that gammaHV68 efficiently establishes latency in B-cell-deficient mice (K. E. Weck, M. L. Barkon, L. I. Yoo, S. H. Speck, and H. W. Virgin, J. Virol. 70:6775-6780, 1996), demonstrating that B cells are not required for gammaHV68 latency. To understand this dichotomy, we determined whether hematopoietic cell types, in addition to B cells, carry latent gammaHV68. We observed a high frequency of cells that reactivate latent gammaHV68 in peritoneal exudate cells (PECs) derived from both B-cell-deficient and normal C57BL/6 mice. PECs were composed primarily of macrophages in B-cell-deficient mice and of macrophages plus B cells in normal C57BL/6 mice. To determine which cells in PECs from C57BL/6 mice carry latent gammaHV68, we developed a limiting-dilution PCR assay to quantitate the frequency of cells carrying the gammaHV68 genome in fluorescence-activated cell sorter-purified cell populations. We also quantitated the contribution of individual cell populations to the total frequency of cells carrying latent gammaHV68. At early times after infection, the frequency of PECs that reactivated gammaHV68 correlated very closely with the frequency of PECs carrying the gammaHV68 genome, validating measurement of the frequency of viral-genome-positive cells as a measure of latency in this cell population. F4/80-positive macrophage-enriched, lymphocyte-depleted PECs harbored most of the gammaHV68 genome and efficiently reactivated gammaHV68, while CD19-positive, B-cell-enriched PECs harbored about a 10-fold lower frequency of gammaHV68 genome-positive cells. CD4-positive, T-cell-enriched PECs contained only a very low frequency of gammaHV68 genome-positive cells, consistent with previous analyses indicating that T cells are not a reservoir for gammaHV68 latency (N. P. Sunil-Chandra, S. Efstathiou, and A. A. Nash, J. Gen. Virol. 73:3275-3279, 1992). Since macrophages are bone marrow derived, we determined whether elicitation of a large inflammatory response in the peritoneum would recruit additional latent cells into the peritoneum. Thioglycolate inoculation increased the total number of PECs by about 20-fold but did not affect the frequency of cells that reactivate gammaHV68, consistent with a bone marrow reservoir for latent gammaHV68. These experiments demonstrate gammaHV68 latency in two different hematopoietic cell types, F4/80-positive macrophages and CD19-positive B cells, and argue for a bone marrow reservoir for latent gammaHV68.     

Antiplatelet and anticoagulant therapy in elective percutaneous coronary intervention

Thrombosis plays a major role in acute vessel closure both after coronary balloon angioplasty and after stenting. This review will address the role of antiplatelet and anticoagulant therapy in preventing early thrombotic complications after percutaneous coronary intervention. The focus will be on agents that are routinely available and commonly used.     

Complete genome sequence of the extremely acidophilic methanotroph isolate V4, Methylacidiphilum infernorum, a representative of the bacterial phylum Verrucomicrobia

Background

The phylum Verrucomicrobia is a widespread but poorly characterized bacterial clade. Although cultivation-independent approaches detect representatives of this phylum in a wide range of environments, including soils, seawater, hot springs and human gastrointestinal tract, only few have been isolated in pure culture. We have recently reported cultivation and initial characterization of an extremely acidophilic methanotrophic member of the Verrucomicrobia, strain V4, isolated from the Hell's Gate geothermal area in New Zealand. Similar organisms were independently isolated from geothermal systems in Italy and Russia.

Results

We report the complete genome sequence of strain V4, the first one from a representative of the Verrucomicrobia. Isolate V4, initially named "Methylokorus infernorum" (and recently renamed Methylacidiphilum infernorum) is an autotrophic bacterium with a streamlined genome of ~2.3 Mbp that encodes simple signal transduction pathways and has a limited potential for regulation of gene expression. Central metabolism of M. infernorum was reconstructed almost completely and revealed highly interconnected pathways of autotrophic central metabolism and modifications of C₁-utilization pathways compared to other known methylotrophs. The M. infernorum genome does not encode tubulin, which was previously discovered in bacteria of the genus Prosthecobacter, or close homologs of any other signature eukaryotic proteins. Phylogenetic analysis of ribosomal proteins and RNA polymerase subunits unequivocally supports grouping Planctomycetes, Verrucomicrobia and Chlamydiae into a single clade, the PVC superphylum, despite dramatically different gene content in members of these three groups. Comparative-genomic analysis suggests that evolution of the M. infernorum lineage involved extensive horizontal gene exchange with a variety of bacteria. The genome of M. infernorum shows apparent adaptations for existence under extremely acidic conditions including a major upward shift in the isoelectric points of proteins.

Conclusion

The results of genome analysis of M. infernorum support the monophyly of the PVC superphylum. M. infernorum possesses a streamlined genome but seems to have acquired numerous genes including those for enzymes of methylotrophic pathways via horizontal gene transfer, in particular, from Proteobacteria.

Reviewers

This article was reviewed by John A. Fuerst, Ludmila Chistoserdova, and Radhey S. Gupta.     

Functional significance of adult neurogenesis

'Function' is the key criterion for determining whether adult neurogenesis - be it endogenous, induced, or after transplantation - is successful and has truly generated new nerve cells. Function, however, is an elusive and problematic term. A satisfying statement of function will require evaluation on the three conceptual levels of cells, networks, and systems - and potentially even beyond, on the level of psychology. Neuronal development is a lengthy process, a fact that must be considered when judging causes and consequences in experiments that address function and function-dependent regulation of adult neurogenesis. Nevertheless, the information that has been obtained and published so far provides ample evidence that neurons generated in the adult can function and even suggests how they might contribute to cognitive processes.