36 research outputs found
Coordinated optimization of visual cortical maps (I) Symmetry-based analysis
In the primary visual cortex of primates and carnivores, functional
architecture can be characterized by maps of various stimulus features such as
orientation preference (OP), ocular dominance (OD), and spatial frequency. It
is a long-standing question in theoretical neuroscience whether the observed
maps should be interpreted as optima of a specific energy functional that
summarizes the design principles of cortical functional architecture. A
rigorous evaluation of this optimization hypothesis is particularly demanded by
recent evidence that the functional architecture of OP columns precisely
follows species invariant quantitative laws. Because it would be desirable to
infer the form of such an optimization principle from the biological data, the
optimization approach to explain cortical functional architecture raises the
following questions: i) What are the genuine ground states of candidate energy
functionals and how can they be calculated with precision and rigor? ii) How do
differences in candidate optimization principles impact on the predicted map
structure and conversely what can be learned about an hypothetical underlying
optimization principle from observations on map structure? iii) Is there a way
to analyze the coordinated organization of cortical maps predicted by
optimization principles in general? To answer these questions we developed a
general dynamical systems approach to the combined optimization of visual
cortical maps of OP and another scalar feature such as OD or spatial frequency
preference.Comment: 90 pages, 16 figure
Coverage, Continuity and Visual Cortical Architecture
The primary visual cortex of many mammals contains a continuous
representation of visual space, with a roughly repetitive aperiodic map of
orientation preferences superimposed. It was recently found that orientation
preference maps (OPMs) obey statistical laws which are apparently invariant
among species widely separated in eutherian evolution. Here, we examine whether
one of the most prominent models for the optimization of cortical maps, the
elastic net (EN) model, can reproduce this common design. The EN model
generates representations which optimally trade of stimulus space coverage and
map continuity. While this model has been used in numerous studies, no
analytical results about the precise layout of the predicted OPMs have been
obtained so far. We present a mathematical approach to analytically calculate
the cortical representations predicted by the EN model for the joint mapping of
stimulus position and orientation. We find that in all previously studied
regimes, predicted OPM layouts are perfectly periodic. An unbiased search
through the EN parameter space identifies a novel regime of aperiodic OPMs with
pinwheel densities lower than found in experiments. In an extreme limit,
aperiodic OPMs quantitatively resembling experimental observations emerge.
Stabilization of these layouts results from strong nonlocal interactions rather
than from a coverage-continuity-compromise. Our results demonstrate that
optimization models for stimulus representations dominated by nonlocal
suppressive interactions are in principle capable of correctly predicting the
common OPM design. They question that visual cortical feature representations
can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
New susceptibility loci associated with kidney disease in type 1 diabetes
WOS:000309817900008Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.Peer reviewe
Analysis of the elastic net model applied to the formation of ocular dominance and orientation columns
The development and structure of orientation (OR) and ocular dominance (OD) maps in the primary visual cortex of cats and monkeys can be modelled using the elastic net algorithm, which attempts to iind an 'optimal' cortical representation of the input features. Here we analyse this behaviour in terms of parameters of the feature space. We derive expressions for the OR periodicity, and the first bifurcation point as a function of the annealing parameter using the methods of Durbin et al (Durbin R, Szeliski R and Yuille A 1989 Neural Computation 1 348-58). We also investigate the effect of the relative order of OR and OD development on overall map structure. This analysis suggests that developmental order can be predicted from the final OR and OD periodicities. In conjunction with experimentally measured values for these periodicities, the model predicts that (i) in normal macaques OD develops first, (ii) in normal cats OR develops first and (iii) in strabismic cats OD develops first
DELAYED FEEDBACK SUPPRESSION OF COLLECTIVE RHYTHMIC ACTIVITY IN
We analyze the delayed feedback approach to suppression of collective synchrony in a population of globally or randomly coupled neurons. In particular, we consider the main factors of imperfection of the control scheme and their influence on the suppression efficiency. Next, with the help of a realistic model of synaptically coupled population of inhibitory and excitatory neurons we demonstrate the potential of the suppression scheme for neurophysiological applications
Hemochromatosis associated with endothelial dysfunction: Evidence for the role of iron stores in early atherogenesis
Impaired endothelium-dependent, flow-mediated dilatation of the brachial artery was observed in a 50-year-old premenopausal female non-smoker with idiopathic hemochromatosis. Endothelial dysfunction observed in this patient supports a relationship between body iron stores and early atherosclerotic process
Molecular analysis of the estrogen receptor alpha gene in men with coronary artery disease: association with disease status
Background: The vasoprotective effects of estrogens are known to be
mediated by their respective estrogen receptors (ER) alpha (ERalpha) and
beta (ERbeta), which are present on the vascular wall. The
amino-terminal part of the ERalpha appears to be important; genetic
alterations in this region have been associated with arterial
hypertension. This region has not been studied in atherosclerotic
disease. In the present study, we examined the association between
coronary artery disease (CAD) and alterations of the NH2-terminal part
of ERalpha coding region. Methods: Genomic DNA was isolated from 50
healthy men and 40 men with CAD confirmed by coronary angiography. The
coding sequences of exons 1 and 2 were amplified by polymerase chain
reaction (PCR) and analyzed by either denaturing gradient gel
electrophoresis (DGGE) or single stranded conformational polymorphism
(SSCP), or both, sequencing and restriction fragment length polymorphism
(RFLP), as appropriate. In the same subjects, biochemical and vascular
parameters were also determined by using the appropriate methodology.
Results: In exon 1, the codon 10 polymorphism was detected in both
patients and healthy men either in heterozygous or homozygous form. The
codon 87 polymorphism was detected mainly in homozygous form and only
five individuals were heterozygotes. No mutations were found in exon 2.
Statistical analysis of the allele distribution for either codon 10 or
87 between patients and healthy men showed no significant difference. In
patients, the biochemical parameters were not statistically
significantly different between ERalpha codon 10 genotypes or alleles.
However, there was a clear effect of the TCT/TCT genotype and TCT allele
on the vascular parameters whereas the right internal carotid artery
(RICA) intima-media thickness was significantly associated with TCT/TCT
genotype and TCT allele. Conclusions: We conclude that ERalpha genotypes
play no role in the incidence of CAD disease, however, ERalpha codon 10
may be a genetic factor controlling some vessels’ angiographic
complications. (C) 2003 Elsevier Science B.V. All rights reserved