Ensemble Place Codes in Hippocampus: CA1, CA3, and Dentate Gyrus Place Cells Have Multiple Place Fields in Large Environments

Previously we reported that the hippocampus place code must be an ensemble code because place cells in the CA1 region of hippocampus have multiple place fields in a more natural, larger-than-standard enclosure with stairs that permitted movements in 3-D. Here, we further investigated the nature of hippocampal place codes by characterizing the spatial firing properties of place cells in the CA1, CA3, and dentate gyrus (DG) hippocampal subdivisions as rats foraged in a standard 76-cm cylinder as well as a larger-than-standard box (1.8 m×1.4 m) that did not have stairs or any internal structure to permit movements in 3-D. The rats were trained to forage continuously for 1 hour using computer-controlled food delivery. We confirmed that most place cells have single place fields in the standard cylinder and that the positional firing pattern remapped between the cylinder and the large enclosure. Importantly, place cells in the CA1, CA3 and DG areas all characteristically had multiple place fields that were irregularly spaced, as we had reported previously for CA1. We conclude that multiple place fields are a fundamental characteristic of hippocampal place cells that simplifies to a single field in sufficiently small spaces. An ensemble place code is compatible with these observations, which contradict any dedicated coding scheme

Response Monitoring in De Novo Patients with Parkinson's Disease

BACKGROUND: Parkinson's disease (PD) is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD"). METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs) in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne) are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc) are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD

Design of the PROCON trial: a prospective, randomized multi – center study comparing cervical anterior discectomy without fusion, with fusion or with arthroplasty

BACKGROUND: PROCON was designed to assess the clinical outcome, development of adjacent disc disease and costs of cervical anterior discectomy without fusion, with fusion using a stand alone cage and implantation of a Bryan's disc prosthesis. Description of rationale and design of PROCON trial and discussion of its strengths and limitations. METHODS/DESIGN: Since proof justifying the use of implants or arthroplasty after cervical anterior discectomy is lacking, PROCON was designed. PROCON is a multicenter, randomized controlled trial comparing cervical anterior discectomy without fusion, with fusion with a stand alone cage or with implantation of a disc. The study population will be enrolled from patients with a single level cervical disc disease without myelopathic signs. Each treatment arm will need 90 patients. The patients will be followed for a minimum of five years, with visits scheduled at 6 weeks, 3 months, 12 months, and then yearly. At one year postoperatively, clinical outcome and self reported outcomes will be evaluated. At five years, the development of adjacent disc disease will be investigated. DISCUSSION: The results of this study will contribute to the discussion whether additional fusion or arthroplasty is needed and cost effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN4168184

Detection of copy number variations in rice using array-based comparative genomic hybridization

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) can create new genes, change gene dosage, reshape gene structures, and modify elements regulating gene expression. As with all types of genetic variation, CNVs may influence phenotypic variation and gene expression. CNVs are thus considered major sources of genetic variation. Little is known, however, about their contribution to genetic variation in rice.</p> <p>Results</p> <p>To detect CNVs, we used a set of NimbleGen whole-genome comparative genomic hybridization arrays containing 718,256 oligonucleotide probes with a median probe spacing of 500 bp. We compiled a high-resolution map of CNVs in the rice genome, showing 641 CNVs between the genomes of the rice cultivars 'Nipponbare' (from <it>O. sativa </it>ssp. <it>japonica</it>) and 'Guang-lu-ai 4' (from <it>O. sativa </it>ssp. <it>indica</it>). The CNVs identified vary in size from 1.1 kb to 180.7 kb, and encompass approximately 7.6 Mb of the rice genome. The largest regions showing copy gain and loss are of 37.4 kb on chromosome 4, and 180.7 kb on chromosome 8. In addition, 85 DNA segments were identified, including some genic sequences. Contracted genes greatly outnumbered duplicated ones. Many of the contracted genes corresponded to either the same genes or genes involved in the same biological processes; this was also the case for genes involved in disease and defense.</p> <p>Conclusion</p> <p>We detected CNVs in rice by array-based comparative genomic hybridization. These CNVs contain known genes. Further discussion of CNVs is important, as they are linked to variation among rice varieties, and are likely to contribute to subspecific characteristics.</p

Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis – a CMR study

<p>Abstract</p> <p>Background</p> <p>Myocardial edema is a substantial feature of the inflammatory response in human myocarditis. The relation between myocardial edema and myocardial mass in the course of healing myocarditis has not been systematically investigated. We hypothesised that the resolution of myocardial edema as visualised by T2-weighted cardiovascular magnetic resonance (CMR) is associated with a decrease of myocardial mass in steady state free precession (SSFP)-cine imaging.</p> <p>Methods</p> <p>21 patients with acute myocarditis underwent CMR shortly after onset of symptoms and 1 year later. For visualization of edema, a T2-weighted breath-hold black-blood triple-inversion fast spin echo technique was applied and the ratio of signal intensity of myocardium/skeletal muscle was assessed. Left ventricular (LV) mass, volumes and function were quantified from biplane cine steady state free precession images.</p> <p>11 healthy volunteers served as a control group for interstudy reproducibility of LV mass.</p> <p>Results</p> <p>In patients with myocarditis, a significant decrease in LV mass was observed during follow-up compared to the acute phase (156.7 ± 30.6 g vs. 140.3 ± 28.3 g, p < 0.0001). The reduction of LV mass paralleled the normalization of initially increased myocardial signal intensity on T2-weighted images (2.4 ± 0.4 vs. 1.68 ± 0.3, p < 0.0001).</p> <p>In controls, the interstudy difference of LV mass was lower than in patients (5.1 ± 2.9 g vs. 16.3 ± 14.2 g, p = 0.02) resulting in a lower coefficient of variability (2.1 vs 8.9%, p = 0.04).</p> <p>Conclusion</p> <p>Reversible abnormalities in T2-weighted CMR are paralleled by a transient increase in left ventricular mass during the course of myocarditis. Myocardial edema may be a common pathway explaining these findings.</p

Accuracy of syndrome definitions based on diagnoses in physician claims

<p>Abstract</p> <p>Background</p> <p>Community clinics offer potential for timelier outbreak detection and monitoring than emergency departments. However, the accuracy of syndrome definitions used in surveillance has never been evaluated in community settings. This study's objective was to assess the accuracy of syndrome definitions based on diagnostic codes in physician claims for identifying 5 syndromes (fever, gastrointestinal, neurological, rash, and respiratory including influenza-like illness) in community clinics.</p> <p>Methods</p> <p>We selected a random sample of 3,600 community-based primary care physicians who practiced in the fee-for-service system in the province of Quebec, Canada in 2005-2007. We randomly selected 10 visits per physician from their claims, stratifying on syndrome type and presence, diagnosis, and month. Double-blinded chart reviews were conducted by telephone with consenting physicians to obtain information on patient diagnoses for each sampled visit. The sensitivity, specificity, and positive predictive value (PPV) of physician claims were estimated by comparison to chart review.</p> <p>Results</p> <p>1,098 (30.5%) physicians completed the chart review. A chart entry on the date of the corresponding claim was found for 10,529 (95.9%) visits. The sensitivity of syndrome definitions based on diagnostic codes in physician claims was low, ranging from 0.11 (fever) to 0.44 (respiratory), the specificity was high, and the PPV was moderate to high, ranging from 0.59 (fever) to 0.85 (respiratory). We found that rarely used diagnostic codes had a higher probability of being false-positives, and that more commonly used diagnostic codes had a higher PPV.</p> <p>Conclusions</p> <p>Future research should identify physician, patient, and encounter characteristics associated with the accuracy of diagnostic codes in physician claims. This would enable public health to improve syndromic surveillance, either by focusing on physician claims whose diagnostic code is more likely to be accurate, or by using all physician claims and weighing each according to the likelihood that its diagnostic code is accurate.</p

Detection of amyloid beta aggregates in the brain of BALB/c mice after Chlamydia pneumoniae infection

Neuroinflammation, initiated by cerebral infection, is increasingly postulated as an aetiological factor in neurodegenerative diseases such as Alzheimer’s disease (AD). We investigated whether Chlamydia pneumoniae (Cpn) infection results in extracellular aggregation of amyloid beta (Aβ) in BALB/c mice. At 1 week post intranasal infection (p.i.), Cpn DNA was detected predominantly in the olfactory bulbs by PCR, whereas brains at 1 and 3 months p.i. were Cpn negative. At 1 and 3 months p.i., extracellular Aβ immunoreactivity was detected in the brain of Cpn-infected mice but also in the brain of mock-infected mice and mice that were neither Cpn infected nor mock infected. However, these extracellular Aβ aggregates showed morphological differences compared to extracellular Aβ aggregates detected in the brain of transgenic APP751SL/PS1M146L mice. These data do not unequivocally support the hypothesis that Cpn infection induces the formation of AD-like Aβ plaques in the brain of BALB/c mice, as suggested before. However, future studies are required to resolve these differences and to investigate whether Cpn is indeed an etiological factor in AD pathogenesis

Brain Responses to Violet, Blue, and Green Monochromatic Light Exposures in Humans: Prominent Role of Blue Light and the Brainstem

BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by melanopsin-expressing retinal ganglion cells which are more sensitive to blue light than violet or green light. The contribution of the melanopsin system and the brain mechanisms involved in the establishment of such responses to light remain to be established. METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50 s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a working memory task in fMRI. At light onset, blue light, as compared to green light, increased activity in the left hippocampus, left thalamus, and right amygdala. During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the locus coeruleus. CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of melanopsin-expressing retinal ganglion cells to brain responses to light within the very first seconds of an exposure. The results also demonstrate the implication of the brainstem in mediating these responses in humans and speak for a broad involvement of light in the regulation of brain function

Contribution of copy number variants (CNVs) to congenital, unexplained intellectual and developmental disabilities in Lebanese patients

International audienceBackground: Chromosomal microarray analysis (CMA) is currently the most widely adopted clinical test for patients with unexplained intellectual disability (ID), developmental delay (DD), and congenital anomalies. Its use has revealed the capacity to detect copy number variants (CNVs), as well as regions of homozygosity, that, based on their distribution on chromosomes, indicate uniparental disomy or parental consanguinity that is suggestive of an increased probability of recessive disease. Results: We screened 149 Lebanese probands with ID/DD and 99 healthy controls using the Affymetrix Cyto 2.7 M and SNP6.0 arrays. We report all identified CNVs, which we divided into groups. Pathogenic CNVs were identified in 12.1% of the patients. We review the genotype/phenotype correlation in a patient with a 1q44 microdeletion and refine the minimal critical regions responsible for the 10q26 and 16q monosomy syndromes. Several likely causative CNVs were also detected, including new homozygous microdeletions (9p23p24.1, 10q25.2, and 8p23.1) in 3 patients born to consanguineous parents, involving potential candidate genes. However, the clinical interpretation of several other CNVs remains uncertain, including a microdeletion affecting ATRNL1. This CNV of unknown significance was inherited from the patient's unaffected-mother; therefore, additional ethnically matched controls must be screened to obtain enough evidence for classification of this CNV. Conclusion: This study has provided supporting evidence that whole-genome analysis is a powerful method for uncovering chromosomal imbalances, regardless of consanguinity in the parents of patients and despite the challenge presented by analyzing some CNVs