Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy.

The impact of changes in visual input on neuronal circuitry is complex and much of our knowledge on human brain plasticity of the visual systems comes from animal studies. Reinstating vision in a group of patients with low vision through retinal gene therapy creates a unique opportunity to dynamically study the underlying process responsible for brain plasticity. Historically, increases in the axonal myelination of the visual pathway has been the biomarker for brain plasticity.

Neuroplasticity of the Lateral Geniculate Nucleus in Response to Retinal Gene Therapy in a Group of Patients with Mutations.

Introduction: Previous works on experience-dependent brain plasticity have been limited to the cortical structures, overlooking subcortical visual structures such as the lateral geniculate nucleus (LGN). Animal studies have shown substantial experience dependent plasticity and using fMRI, human studies have demonstrated similar properties in patients with cataract surgery. However, in neither animal nor human studies LGN has not been directly assessed, mainly due to its small size, tissue heterogeneity, low contrast/noise ratio, and low spatial resolution.

Improving the Quantification of the Lateral Geniculate Nucleus in Magnetic Resonance Imaging Using a Novel 3D-Edge Enhancement Technique.

The lateral geniculate nucleus (LGN) is a small, inhomogeneous structure that relays major sensory inputs from the retina to the visual cortex. LGN morphology has been intensively studied due to various retinal diseases, as well as in the context of normal brain development. However, many of the methods used for LGN structural evaluations have not adequately addressed the challenges presented by the suboptimal routine MRI imaging of this structure.

Compensatory Cross-Modal Plasticity Persists After Sight Restoration.

Sensory deprivation prompts extensive structural and functional reorganizations of the cortex resulting in the occupation of space for the lost sense by the intact sensory systems. This process, known as cross-modal plasticity, has been widely studied in individuals with vision or hearing loss. However, little is known on the neuroplastic changes in restoring the deprived sense.

μ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) encode light intensity and trigger reflexive responses to changes in environmental illumination. In addition to functioning as photoreceptors, ipRGCs are post-synaptic neurons in the inner retina, and there is increasing evidence that their output can be influenced by retinal neuromodulators. Here we show that opioids can modulate light-evoked ipRGC signaling, and we demonstrate that the M1, M2 and M3 types of ipRGCs are immunoreactive for μ-opioid receptors (MORs) in both mouse and rat.

Quantifying the effect of light activated outer and inner retinal inhibitory pathways on glutamate release from mixed bipolar cells.

Inhibition mediated by horizontal and amacrine cells in the outer and inner retina, respectively, are fundamental components of visual processing. Here, our purpose was to determine how these different inhibitory processes affect glutamate release from ON bipolar cells when the retina is stimulated with full-field light of various intensities. Light-evoked membrane potential changes (ΔV ) were recorded directly from axon terminals of intact bipolar cells receiving mixed rod and cone inputs (Mbs) in slices of dark-adapted goldfish retina.

Inhibitory input to the direction-selective ganglion cell is saturated at low contrast.

Direction-selective ganglion cells (DSGCs) respond selectively to motion toward a "preferred" direction, but much less to motion toward the opposite "null" direction. Directional signals in the DSGC depend on GABAergic inhibition and are observed over a wide range of speeds, which precludes motion detection based on a fixed temporal correlation. A voltage-clamp analysis, using narrow bar stimuli similar in width to the receptive field center, demonstrated that inhibition to DSGCs saturates rapidly above a threshold contrast.

Calcium spike-mediated digital signaling increases glutamate output at the visual threshold of retinal bipolar cells.

Most retinal bipolar cells (BCs) transmit visual input from photoreceptors to ganglion cells using graded potentials, but some also generate calcium or sodium spikes. Sodium spikes are thought to increase temporal precision of light-evoked BC signaling; however, the role of calcium spikes in BCs is not fully understood. Here we studied how calcium spikes and graded responses mediate neurotransmitter release from Mb-type BCs, known to produce both.

Nitric oxide mediates activity-dependent plasticity of retinal bipolar cell output via S-nitrosylation.

Coding a wide range of light intensities in natural scenes poses a challenge for the retina: adaptation to bright light should not compromise sensitivity to dim light. Here we report a novel form of activity-dependent synaptic plasticity, specifically, a "weighted potentiation" that selectively increases output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input-output ratio for strong stimuli unaffected. In retinal slice preparation, strong depolarization of bipolar terminals significantly lowered the threshold for calcium spike initiation, which originated from a shift in activation of voltage-gated calcium currents (ICa) to more negative potentials.

Maximizing contrast resolution in the outer retina of mammals.

The outer retina removes the first-order correlation, the background light level, and thus more efficiently transmits contrast. This removal is accomplished by negative feedback from horizontal cell to photoreceptors. However, the optimal feedback gain to maximize the contrast sensitivity and spatial resolution is not known.

[Predominant genotypes of Mycobacterium tuberculosis strains from prisoners in Ozerky].

The correlation of the Beijing/W and LAM strains with multiple drug resistance was studied. The transmissibility of the multidrug-resistant strains of these families was demonstrated.

Association of specific mutations in katG, rpoB, rpsL and rrs genes with spoligotypes of multidrug-resistant Mycobacterium tuberculosis isolates in Russia.

Most multidrug-resistant (MDR) Mycobacterium tuberculosis isolates in Russia belong to the Beijing or Latino-American and Mediterranean (LAM) spoligotype families. The objective of this study was to investigate possible associations between genotype and the frequencies of mutations that confer drug resistance in a population that has two large families of circulating strains. Spoligotyping, IS6110 restriction fragment length polymorphism typing, and sequencing of the katG and rpoB genes, were performed for 217 consecutive MDR M.

[Characteristics of Mycobacterium tuberculosis clinical strains genotype A1].

The Mycobacterium tuberculosis strains of genotype A1 (LAM family, VNTR profile 222222) are often resulted from people with pulmonary tuberculosis, who live in Central Russia. Among strains of this family, drug-resistant strains, including those with simultaneous resistance to isoniazid and rifampicin (MDR), are common. The strains of the genotype A1 tend to spread as clones.

A genome-wide sequence-independent comparative analysis of insertion-deletion polymorphisms in multiple Mycobacterium tuberculosis strains.

We applied an enhanced version of subtractive hybridization for comparative analyses of indel differences between genomes of several Mycobacterium tuberculosis strains widespread in Russian regions, and the H37Rv reference strain. A number of differences were detected and partially analyzed, thus demonstrating the practicality of the approach. A majority of the insertions found were shared by all Russian strains, except for strain 1540 that revealed the highest virulence in animal tests.

Characterization of drug-resistant isolates of Mycobacterium tuberculosis derived from Russian inmates.

Setting: Tuberculosis ward of a prison in Russia.

Objective: Molecular characterization of drug-resistant isolates.

Design: Isolates were collected from all tuberculosis patients occurring in the prison over a 1-year period.

[Spoligotypes of clinical Mycobacterium tuberculosis strains isolated in patients with tuberculosis in the Central Region of Russia].

Spoligotyping and RFLP-IS6110 techniques were used to analyze 353 clinical Mycobacterium tuberculosis strains isolated from patients with tuberculosis in the Central Region of Russia. All spoligotypes were classified according to the international database. Most clinical M.

[Characteristics of clinical isolates of Mycobacterium tuberculosis using molecular biological methods].

A total of 230 clinically drug-resistant and 3 drug-sensitive isolates of M. tuberculosis obtained from patients in Tula and Tula region in 1998-2001 were studied. The RFLP-IS6110 genotyping showed that 52 (30.

[Genetic typing of Mycobacterium tuberculosis strains by spoligotyping and genome fingerprinting techniques].

A total of 122 M. tuberculosis clinical drug-resistant strains isolated in Central Russia were studied by spoligotyping and genome fingerprinting techniques. According to spoligotyping results 77% of M.