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

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

Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse

Sensory inputs frequently converge on the brain in a spatially organized manner, often with overlapping inputs to multiple target neurons. Whether the responses of target neurons with common inputs become decorrelated depends on the contribution of local circuit interactions. We addressed this issue in the olfactory system using newly generated transgenic mice that express channelrhodopsin-2 in all of the olfactory sensory neurons. By selectively stimulating individual glomeruli with light, we identified mitral/tufted cells that receive common input (sister cells). Sister cells had highly correlated responses to odors, as measured by average spike rates, but their spike timing in relation to respiration was differentially altered. In contrast, non-sister cells correlated poorly on both of these measures. We suggest that sister mitral/tufted cells carry two different channels of information: average activity representing shared glomerular input and phase-specific information that refines odor representations and is substantially independent for sister cells