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

Automated operant assessments of Huntington's Disease mouse models

Huntington’s disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD

MUC1 expression and anti-MUC1 serum immune response in head and neck squamous cell carcinoma (HNSCC): a multivariate analysis

BACKGROUND: HNSCC progression to adjacent tissue and nodes may be mediated by altered glycoproteins and glycolipids such as MUC1 mucin. This report constitutes a detailed statistical study about MUC1 expression and anti-MUC1 immune responses in relation to different clinical and pathological parameters which may be useful to develop new anti HNSCC therapeutic strategies. PATIENTS AND METHODS: Fifty three pre treatment HNSCC patients were included: 26 (49.1%) bearing oral cavity tumors, 17 (32.1%) localized in the larynx and 10 (18.8%) in the pharynx. Three patients (5.7%) were at stage I, 5 (9.4%) stage II, 15 (28.3%) stage III and 30 (56.6%) at stage IV. MUC1 tumor expression was studied by immunohistochemistry employing two anti-MUC1 antibodies: CT33, anti cytoplasmic tail MUC1 polyclonal antibody (Ab) and C595 anti-peptidic core MUC1 monoclonal antibody. Serum levels of MUC1 and free anti-MUC1 antibodies were detected by ELISA and circulating immune complexes (CIC) by precipitation in polyethylene glycol (PEG) 3.5%; MUC1 isolation from circulating immune complexes was performed by protein A-sepharose CL-4B affinity chromatography followed by SDS-PAGE and Western blot. Statistical analysis consisted in Multivariate Principal Component Analysis (PCA); ANOVA test (Tukey's test) was employed to find differences among groups; nonparametrical correlations (Kendall's Tau) were applied when necessary. Statistical significance was set to p < 0.05 in all cases. RESULTS: MUC1 cytoplasmic tail was detected in 40/50 (80%) and MUC1 protein core in 9/50 (18%) samples while serum MUC1 levels were elevated in 8/53 (15%) patients. A significant statistical correlation was found between MUC1 serum levels and anti-MUC1 IgG free antibodies, while a negative correlation between MUC1 serum levels and anti-MUC1 IgM free antibodies was found. Circulating immune complexes were elevated in 16/53 (30%) samples and were also statistically associated with advanced tumor stage. MUC1 was identified as an antigenic component of IgG circulating immune complexes. Moreover, poorly differentiated tumors were inversely correlated with tumor and serum MUC1 detection and positively correlated with node involvement and tumor mass. CONCLUSION: Possibly, tumor cells produce MUC1 mucin which is liberated to the circulation and captured by IgG antibodies forming MUC1-IgG-CIC. Another interesting conclusion is that poorly differentiated tumors are inversely correlated with tumor and serum MUC1 detection

Environmental enrichment facilitates long-term potentiation in embryonic striatal grafts

Background. Housing animals in an enriched environment improves motor and cognitive performance and anatomical connectivity in rodent lesion models of Huntington disease and transplantation of embryonic striatal grafts. Objective. The authors evaluate the extent to which environmental enrichment can modify synaptic plasticity in the host-graft neuronal circuitry to try to find a physiological substrate for the observed improvements. Methods. C57BL/6 mice, housed in enriched or standard environments, received unilateral quinolinic acid lesions of the striatum, followed by embryonic striatal grafts. Then, 3 months posttransplantation, synaptic physiology and plasticity were evaluated by extracellular recording from in vitro striatal slices. Results. Environmental enrichment had no effect on the chance of long-term depression (LTD) induction or expression of LTD from either normal or grafted striatum. In contrast, enrichment increased the chance of long-term potentiation (LTP) induction and level of expression associated with increased levels of brain-derived neurotrophic factor within both the intact and grafted striatum compared with levels in the striatum of animals housed in standard environments. Conclusions. Environmental enrichment induces changes in host-graft corticostriatal LTP, thus providing a potential physiological substrate for the enrichment-induced improvement in motor and cognitive performance. The effect may be mediated by modulation of the trophic environment in which the grafted cells develop and integrate

Astroglia and graft vascularization following intracerebral transplantation in a Parkinson`s disease model

The integration of transplanted neural cells with the host brain does not only depend on the newly formed syn­aptic connections. Vascularization of the graft tissue is crucial for its survival. Despite this, it is known that host glial cells actively interact with the grafted tissue. No extensive study of the glial reaction following intracerebral transplantation and its relationship with angiogenesis has been carried out.The present study aims to elucidate the role of astroglia in the formation of new vessels following intracerebral transplantation in a rodent model of Parkinson`s disease. We investigate the qualitative and quantitative charac­teristics of GFAP immunoreactivity around grafts and around zones of influence of the transplantation cannula at only two time points - day 7 and day 28 following transplantation.Our findings demonstrate the formation of new blood vessels in graft cores and penetrating the graft-host inter­face on day 28 following transplantation. Moreover, astrogliosis surrounding grafts is more pronounced on day 28 following transplantation, as compared to day 7.These results imply that astrocytes actively participate in the integration of intracerebral grafts. Their presence around newly formed vessels is considered an evidence for the functional maturity of these vessels. The intensive astrogliosis along the graft-host interface can be discussed as a sign of presence of a microcirculatory bed, and therefore for an organotypic integration of the grafts. Clarification of the exact sequence of events in the vascu­larization process and mechanisms of interaction between astroglia, neurons, and endothelium will shed light on the processes of CNS restoration through transplantation