Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb -- the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells -- are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures

Encoding Odorant Identity by Spiking Packets of Rate-Invariant Neurons in Awake Mice

Background: How do neural networks encode sensory information? Following sensory stimulation, neural coding is commonly assumed to be based on neurons changing their firing rate. In contrast, both theoretical works and experiments in several sensory systems showed that neurons could encode information as coordinated cell assemblies by adjusting their spike timing and without changing their firing rate. Nevertheless, in the olfactory system, there is little experimental evidence supporting such model. Methodology/Principal Findings: To study these issues, we implanted tetrodes in the olfactory bulb of awake mice to record the odorant-evoked activity of mitral/tufted (M/T) cells. We showed that following odorant presentation, most M/T neurons do not significantly change their firing rate over a breathing cycle but rather respond to odorant stimulation by redistributing their firing activity within respiratory cycles. In addition, we showed that sensory information can be encoded by cell assemblies composed of such neurons, thus supporting the idea that coordinated populations of globally rateinvariant neurons could be efficiently used to convey information about the odorant identity. We showed that different coding schemes can convey high amount of odorant information for specific read-out time window. Finally we showed that the optimal readout time window corresponds to the duration of gamma oscillations cycles. Conclusion: We propose that odorant can be encoded by population of cells that exhibit fine temporal tuning of spiking activity while displaying weak or no firing rate change. These cell assemblies may transfer sensory information in spikin

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

A force-generating machinery maintains the spindle at the cell center during mitosis.

The position and orientation of the mitotic spindle is precisely regulated to ensure the accurate partition of the cytoplasm between daughter cells and the correct localization of the daughters within growing tissue. Using magnetic tweezers to perturb the position of the spindle in intact cells, we discovered a force-generating machinery that maintains the spindle at the cell center during metaphase and anaphase in one- and two-cell Caenorhabditis elegans embryos. The forces increase with the number of microtubules and are larger in smaller cells. The machinery is rigid enough to suppress thermal fluctuations to ensure precise localization of the mitotic spindle, yet compliant enough to allow molecular force generators to fine-tune the position of the mitotic spindle to facilitate asymmetric division

Effect of instruction, surface stability, and load intensity on trunk muscle activity

The aim of this study was to assess the effect of verbal instruction, surface stability, and load intensity on trunk muscle activity levels during the free weight squat exercise. Twelve trained males performed a free weight squat under four conditions: (1) standing on stable ground lifting 50% of their 1-repetition maximum (RM), (2) standing on a BOSU balance trainer lifting 50% of their 1-RM, (3) standing on stable ground lifting 75% of their 1-RM, and (4) receiving verbal instructions to activate the trunk muscles followed by lifting 50% of their 1-RM. Surface EMG activity from muscles rectus abdominis (RA), external oblique (EO), transversus abdominis/internal oblique (TA/IO), and erector spinae (ES) were recorded for each condition and normalized for comparisons. Muscles RA, EO, and TA/IO displayed greater peak activity (39-167%) during squats with instructions compared to the other squat conditions (P=0.04-0.007). Peak EMG activity of muscle ES was greater for the 75% 1-RM condition than squats with instructions or lifting 50% of 1-RM (P=0.04-0.02). The results indicate that if the goal is to enhance EMG activity of the abdominal muscles during a multi-joint squat exercise then verbal instructions may be more effective than increasing load intensity or lifting on an unstable surface. However, in light of other research, conscious co-activation of the trunk muscles during the squat exercise may lead to spinal instability and hazardous compression forces in the lumbar spine

Precision and diversity in an odor map on the olfactory bulb

We explored the map of odor space created by glomeruli on the olfactory bulb of both rat and mouse. Identified glomeruli could be matched across animals by their response profile to hundreds of odors. Their layout in different individuals varied by only ~1 glomerular spacing, corresponding to a precision of 1 part in 1,000. Across species, mouse and rat share many glomeruli with apparently identical odor tuning, arranged in a similar layout. In mapping the position of a glomerulus to its odor tuning, we found only a coarse relationship with a precision of ~5 spacings. No chemotopic order was apparent on a finer scale and nearby glomeruli were almost as diverse in their odor sensitivity as distant ones. This local diversity of sensory tuning stands in marked distinction from other brain maps. Given the reliable placement of the glomeruli, it represents a feature, not a flaw, of the olfactory bulb.Molecular and Cellular Biolog

Precise olfactory responses tile the sniff cycle

In terrestrial vertebrates, sniffing controls odorant access to receptors, and therefore sets the timescale of olfactory stimuli. We found that odorants evoked precisely sniff-locked activity in mitral/tufted cells in the olfactory bulb of awake mouse. The trial-to-trial response jitter averaged 12 ms, a precision comparable to other sensory systems. Individual cells expressed odor-specific temporal patterns of activity and, across the population, onset times tiled the duration of the sniff cycle. Responses were more tightly time-locked to the sniff phase than to the time after inhalation onset. The spikes of single neurons carried sufficient information to discriminate odors. In addition, precise locking to sniff phase may facilitate ensemble coding by making synchrony relationships across neurons robust to variation in sniff rate. The temporal specificity of mitral/tufted cell output provides a potentially rich source of information for downstream olfactory areas