Diversity of Ganglion Cell Responses to Saccade-Like Image Shifts in the Primate Retina.

Saccades are a fundamental part of natural vision. They interrupt fixations of the visual gaze and rapidly shift the image that falls onto the retina. These stimulus dynamics can cause activation or suppression of different retinal ganglion cells, but how they affect the encoding of visual information in different types of ganglion cells is largely unknown.

Optogenetic restoration of high sensitivity vision with bReaChES, a red-shifted channelrhodopsin.

The common final pathway to blindness in many forms of retinal degeneration is the death of the light-sensitive primary retinal neurons. However, the normally light-insensitive second- and third-order neurons persist optogenetic gene therapy aims to restore sight by rendering such neurons light-sensitive. Here, we investigate whether bReaChES, a newly described high sensitivity Type I opsin with peak sensitivity to long-wavelength visible light, can restore vision in a murine model of severe early-onset retinal degeneration.

Tonic Endocannabinoid Levels Modulate Retinal Signaling.

The endocannabinoid (eCB) system is critically involved in the modulation of synaptic transmission in the central nervous system, playing an important role in the control of emotional responses, neurodevelopment and synaptic plasticity among other functions. The eCB system is also present in the retina, with studies indicating changes in function after application of cannabinoid receptor agonists, antagonists and in knockout models. Whether eCBs are tonically released in the retina and their physiological functions is, however, still unknown.

Rapid Analysis of Visual Receptive Fields by Iterative Tomography.

Many receptive fields in the early visual system show standard (center-surround) structure and can be analyzed using simple drifting patterns and a difference-of-Gaussians (DoG) model, which treats the receptive field as a linear filter of the visual image. But many other receptive fields show nonlinear properties such as selectivity for direction of movement. Such receptive fields are typically studied using discrete stimuli (moving or flashed bars and edges) and are modelled according to the features of the visual image to which they are most sensitive.

The temporal structure of the inner retina at a single glance.

The retina decomposes visual stimuli into parallel channels that encode different features of the visual environment. Central to this computation is the synaptic processing in a dense layer of neuropil, the so-called inner plexiform layer (IPL). Here, different types of bipolar cells stratifying at distinct depths relay the excitatory feedforward drive from photoreceptors to amacrine and ganglion cells.

Cannabinoids Modulate Light Signaling in ON-Sustained Retinal Ganglion Cells of the Mouse.

The sole output of the retina to the brain is a signal that results from the integration of excitatory and inhibitory synaptic inputs at the level of retinal ganglion cells (RGCs). Endogenous cannabinoids (eCBs) are found throughout the central nervous system where they modulate synaptic excitability. Cannabinoid receptors and their ligands have been localized to most retinal neurons in mammals, yet their impact on retinal processing is not well known.

Optogenetic approaches to vision restoration.

Inherited retinal disease (IRD) affects about 1 in 3000 to 1 in 5000 individuals and is now believed to be the most common cause of blindness registration in developed countries. Until recently, the management of such conditions had been exclusively supportive. However, advances in molecular biology and medical engineering have now seen the rise of a variety of approaches to restore vision in patients with IRDs.

Cannabinoid-induced increase of quantal size and enhanced neuromuscular transmission.

Cannabinoids exert dynamic control over many physiological processes including memory formation, cognition and pain perception. In the central nervous system endocannabinoids mediate negative feedback of quantal transmitter release following postsynaptic depolarization. The influence of cannabinoids in the peripheral nervous system is less clear and might have broad implications for the therapeutic application of cannabinoids.

A Model for Developing Clinical Analytics Capacity: Closing the Loops on Outcomes to Optimize Quality.

Closed Loop Analytics© is receiving growing interest in healthcare as a term referring to information technology, local data and clinical analytics working together to generate evidence for improvement. The Closed Loop Analytics model consists of three loops corresponding to the decision-making levels of an organization and the associated data within each loop - Patients, Protocols, and Populations. The authors propose that each of these levels should utilize the same ecosystem of electronic health record (EHR) and enterprise data warehouse (EDW) enabled data, in a closed-loop fashion, with that data being repackaged and delivered to suit the analytic and decision support needs of each level, in support of better outcomes.

The impact of inhibitory mechanisms in the inner retina on spatial tuning of RGCs.

Spatial tuning properties of retinal ganglion cells (RGCs) are sharpened by lateral inhibition originating at both the outer and inner plexiform layers. Lateral inhibition in the retina contributes to local contrast enhancement and sharpens edges. In this study, we used dynamic clamp recordings to examine the contribution of inner plexiform inhibition, originating from spiking amacrine cells, to the spatial tuning of RGCs.

Vestibular Interactions in the Thalamus.

It has long been known that the vast majority of all information en route to the cerebral cortex must first pass through the thalamus. The long held view that the thalamus serves as a simple hi fidelity relay station for sensory information to the cortex, however, has over recent years been dispelled. Indeed, multiple projections from the vestibular nuclei to thalamic nuclei (including the ventrobasal nuclei, and the geniculate bodies)- regions typically associated with other modalities- have been described.

Inner retinal inhibition shapes the receptive field of retinal ganglion cells in primate.

The centre-surround organisation of receptive fields is a feature of most retinal ganglion cells (RGCs) and is critical for spatial discrimination and contrast detection. Although lateral inhibitory processes are known to be important in generating the receptive field surround, the contribution of each of the two synaptic layers in the primate retina remains unclear. Here we studied the spatial organisation of excitatory and inhibitory synaptic inputs onto ON and OFF ganglion cells in the primate retina.

Characterization of secretagogin-immunoreactive amacrine cells in marmoset retina.

The retina contains at least 30 different types of amacrine cells but not many are well characterized. In the present study the calcium-binding protein secretagogin was localized in a population of regular and displaced amacrine cells in the retina of the common marmoset Callithrix jacchus. Irrespective of their soma location, the dendrites of secretagogin amacrine cells occupy strata 2, 3, and 4 of the inner plexiform layer, between the two bands formed by cholinergic amacrine cells.

Excitatory and inhibitory contributions to receptive fields of alpha-like retinal ganglion cells in mouse.

The ON and OFF pathways that emerge at the first synapse in the retina are generally thought to be streamed in parallel to higher visual areas, but recent work shows cross talk at the level of retinal ganglion cells. The ON pathway drives inhibitory inputs onto some OFF ganglion cells, such that these neurons show "push-pull" convergence of OFF-excitation and ON-disinhibition. In this study we measure the spatial receptive field of excitatory and inhibitory inputs to OFF-sustained (OFF-S) retinal ganglion cells of mouse, establish how contrast adaptation modulates excitatory and inhibitory synaptic inputs, and show the pharmacology of the inhibitory inputs.

Implementing dynamic clamp with synaptic and artificial conductances in mouse retinal ganglion cells.

Ganglion cells are the output neurons of the retina and their activity reflects the integration of multiple synaptic inputs arising from specific neural circuits. Patch clamp techniques, in voltage clamp and current clamp configurations, are commonly used to study the physiological properties of neurons and to characterize their synaptic inputs. Although the application of these techniques is highly informative, they pose various limitations.

Responses of retinal ganglion cells to extracellular electrical stimulation, from single cell to population: model-based analysis.

Retinal ganglion cells (RGCs), which survive in large numbers following neurodegenerative diseases, could be stimulated with extracellular electric pulses to elicit artificial percepts. How do the RGCs respond to electrical stimulation at the sub-cellular level under different stimulus configurations, and how does this influence the whole-cell response? At the population level, why have experiments yielded conflicting evidence regarding the extent of passing axon activation? We addressed these questions through simulations of morphologically and biophysically detailed computational RGC models on high performance computing clusters. We conducted the analyses on both large-field RGCs and small-field midget RGCs.

Integrated care, information management and information technology in Canada: have we made any progress in the past 12 years?

A dozen years ago, a seminal article was written by Leatt, Pink and Guerriere that boldly stated that Canada did not have integrated healthcare but, rather, a hodgepodge of disconnected parts! The article also stated categorically that Canadian regional health authorities could not provide comprehensive integrated care since they were not responsible for drugs dispensed from retail pharmacies or for medical care provided by physicians. Twelve years later, some progress toward integrated care has been made, though many would argue that it is both inadequate and disappointing - even if Canada's provincial health systems would like to integrate services across an ever-expanding continuum of care to better serve patients.

Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells.

The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated.

Widespread adoption of information technology in primary care physician offices in Denmark: a case study.

Denmark is one of the world's leading countries in the use of health care technology. Virtually all primary care physicians have electronic medical records with full clinical functionality. Their systems are also connected to a national network, which allows them to electronically send and receive clinical data to and from consultant specialists, hospitals, pharmacies, and other health care providers.

Integrated care needs integrated information management and technology.

Integrated care entails that professionals from different organizations have to work together in a team-oriented way to provide high-quality care for a patient. This requires that healthcare professionals share information about--and with--patients at appropriate points in the care or treatment process. The necessary infrastructural arrangements--such as shared patient records, regional collaboration and a clear, transparent incentive structure--must be in place.

Permanent functional reorganization of retinal circuits induced by early long-term visual deprivation.

Early sensory experience shapes the functional and anatomical connectivity of neuronal networks. Light deprivation alters synaptic transmission and modifies light response properties in the visual system, from retinal circuits to higher visual centers. These effects are more pronounced during a critical period in juvenile life and are mostly reversed by restoring normal light conditions.