Gap junctions fine-tune ganglion cell signals to equalize response kinetics within a given electrically coupled array.

Retinal ganglion cells (RGCs) summate inputs and forward a spike train code to the brain in the form of either maintained spiking (sustained) or a quickly decaying brief spike burst (transient). We report diverse response transience values across the RGC population and, contrary to the conventional transient/sustained scheme, responses with intermediary characteristics are the most abundant. Pharmacological tests showed that besides GABAergic inhibition, gap junction (GJ)-mediated excitation also plays a pivotal role in shaping response transience and thus visual coding.

Extrinsic and Intrinsic Factors Determine Expression Levels of Gap Junction-Forming Connexins in the Mammalian Retina.

Gap junctions (GJs) are not static bridges; instead, GJs as well as the molecular building block connexin (Cx) proteins undergo major expression changes in the degenerating retinal tissue. Various progressive diseases, including retinitis pigmentosa, glaucoma, age-related retinal degeneration, etc., affect neurons of the retina and thus their neuronal connections endure irreversible changes as well.

Molecular Mechanisms of Retinal Degeneration and How to Avoid It.

Vision is the most important sensory modality in vertebrates in general, and as such, it is the most feared sense to lose [...

Serotonin is a gap junction-permeable neuronal tracer in the mouse retina.

Introduction: Gap junctions are dynamically modulated bridges allowing the transcellular passage of ions and small molecules with a molecular mass of up to 1 kDa, a mechanism utilized for molecular communication purposes by living cells. This same mechanism is also exploited by scientists to reveal the existence of gap junction contacts by the cell-to-cell movement of tracers. However, multiple labeling experiments require the availability of multiple gap junction-permeable tracers.

Traumatic Brain Injury Induces Microglial and Caspase3 Activation in the Retina.

Traumatic brain injury (TBI) is among the main causes of sudden death after head trauma. These injuries can result in severe degeneration and neuronal cell death in the CNS, including the retina, which is a crucial part of the brain responsible for perceiving and transmitting visual information. The long-term effects of mild-repetitive TBI (rmTBI) are far less studied thus far, even though damage induced by repetitive injuries occurring in the brain is more common, especially amongst athletes.

Transience of the Retinal Output Is Determined by a Great Variety of Circuit Elements.

Retinal ganglion cells (RGCs) encrypt stimulus features of the visual scene in action potentials and convey them toward higher visual centers in the brain. Although there are many visual features to encode, our recent understanding is that the ~46 different functional subtypes of RGCs in the retina share this task. In this scheme, each RGC subtype establishes a separate, parallel signaling route for a specific visual feature (e.

LED-Induced Microglial Activation and Rise in Caspase3 Suggest a Reorganization in the Retina.

Vision is our primary sense as the human eye is the gateway for more than 65% of information reaching the human brain. Today's increased exposure to different wavelengths and intensities of light from light emitting diode (LED) sources could induce retinal degeneration and accompanying neuronal cell death. Damage induced by chronic phototoxic reactions occurring in the retina accumulates over years and it has been suggested as being responsible for the etiology of many debilitating ocular conditions.

Regional Variation of Gap Junctional Connections in the Mammalian Inner Retina.

The retinas of many species show regional specialisations that are evident in the differences in the processing of visual input from different parts of the visual field. Regional specialisation is thought to reflect an adaptation to the natural visual environment, optical constraints, and lifestyle of the species. Yet, little is known about regional differences in synaptic circuitry.

The role of gap junctions in cell death and neuromodulation in the retina.

Vision altering diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, myopia, retinal vascular disease, traumatic brain injuries and others cripple many lives and are projected to continue to cause anguish in the foreseeable future. Gap junctions serve as an emerging target for neuromodulation and possible regeneration as they directly connect healthy and/or diseased cells, thereby playing a crucial role in pathophysiology. Since they are permeable for macromolecules, able to cross the cellular barriers, they show duality in illness as a cause and as a therapeutic target.

Molecular Biology of Retinal Ganglion Cells.

The main goal of this thematic issue was to bring both original research papers and reviews together to provide an insight into the rather broad topic of molecular biology of retinal ganglion cells (RGCs) [...

Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model.

All neurodegenerative diseases involve a relatively long period of timeframe from the onset of the disease to complete loss of functions. Extending this timeframe, even at a reduced level of function, would improve the quality of life of patients with these devastating diseases. The retina, as the part of the central nervous system and a frequent site of many distressing neurodegenerative disease, provides an ideal model to investigate the feasibility of extending the functional timeframe through pharmacologic intervention.

Imatinib Sets Pericyte Mosaic in the Retina.

The nervous system demands an adequate oxygen and metabolite exchange, making pericytes (PCs), the only vasoactive cells on the capillaries, essential to neural function. Loss of PCs is a hallmark of multiple diseases, including diabetes, Alzheimer's, amyotrophic lateral sclerosis (ALS) and Parkinson's. Platelet-derived growth factor receptors (PDGFRs) have been shown to be critical to PC function and survival.

Spatial Expression Pattern of the Major Ca-Buffer Proteins in Mouse Retinal Ganglion Cells.

The most prevalent Ca-buffer proteins (CaBPs: parvalbumin-PV; calbindin-CaB; calretinin-CaR) are widely expressed by various neurons throughout the brain, including the retinal ganglion cells (RGCs). Even though their retinal expression has been extensively studied, a coherent assessment of topographical variations is missing. To examine this, we performed immunohistochemistry (IHC) in mouse retinas.

Response Latency Tuning by Retinal Circuits Modulates Signal Efficiency.

In the visual system, retinal ganglion cells (RGCs) of various subtypes encode preprocessed photoreceptor signals into a spike output which is then transmitted towards the brain through parallel feature pathways. Spike timing determines how each feature signal contributes to the output of downstream neurons in visual brain centers, thereby influencing efficiency in visual perception. In this study, we demonstrate a marked population-wide variability in RGC response latency that is independent of trial-to-trial variability and recording approach.

Connexin-36 distribution and layer-specific topography in the cat retina.

Connexin-36 (Cx36) is the major constituent of mammalian retinal gap junctions positioned in key signal pathways. Here, we examined the laminar and large-scale topographical distribution of Cx36 punctate immunolabels in the retina of the cat, a classical model of the mammalian visual system. Calretinin-immunoreactive (CaR-IR) cell populations served to outline the nuclear and plexiform layers and to stain specific neuronal populations.

Expression of Ca-Binding Buffer Proteins in the Human and Mouse Retinal Neurons.

Ca-binding buffer proteins (CaBPs) are widely expressed by various neurons throughout the central nervous system (CNS), including the retina. While the expression of CaBPs by photoreceptors, retinal interneurons and the output ganglion cells in the mammalian retina has been extensively studied, a general description is still missing due to the differences between species, developmental expression patterns and study-to-study discrepancies. Furthermore, CaBPs are occasionally located in a compartment-specific manner and two or more CaBPs can be expressed by the same neuron, thereby sharing the labor of Ca buffering in the intracellular milieu.

Strategic Positioning of Connexin36 Gap Junctions Across Human Retinal Ganglion Cell Dendritic Arbors.

Connexin36 (Cx36) subunits form gap junctions (GJ) between neurons throughout the central nervous system. Such GJs of the mammalian retina serve the transmission, averaging and correlation of signals prior to conveying visual information to the brain. Retinal GJs have been exhaustively studied in various animal species, however, there is still a perplexing paucity of information regarding the presence and function of human retinal GJs.

Transiency of retinal ganglion cell action potential responses determined by PSTH time constant.

Retinal ganglion cells (RGC) have been described to react to light stimuli either by producing short bursts of spikes or by maintaining a longer, continuous train of action potentials. Fast, quickly decaying responses are considered to be transient in nature and encode information about movement and direction, while cell responses that show a slow, drawn-out response fall into the sustained category and are thought to be responsible for carrying information related to color and contrast. Multiple approaches have been introduced thus far to measure and determine response transiency.

Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison.

Much knowledge about interconnection of human retinal neurons is inferred from results on animal models. Likewise, there is a lack of information on human retinal electrical synapses/gap junctions (GJ). Connexin36 (Cx36) forms GJs in both the inner and outer plexiform layers (IPL and OPL) in most species including humans.

Bipolar cell gap junctions serve major signaling pathways in the human retina.

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models.

Inhibitory masking controls the threshold sensitivity of retinal ganglion cells.

Key Points: Retinal ganglion cells (RGCs) in dark-adapted retinas show a range of threshold sensitivities spanning ∼3 log units of illuminance. Here, we show that the different threshold sensitivities of RGCs reflect an inhibitory mechanism that masks inputs from certain rod pathways. The masking inhibition is subserved by GABA receptors, probably on bipolar cell axon terminals.

Calcium buffer proteins are specific markers of human retinal neurons.

Ca(2+)-buffer proteins (CaBPs) modulate the temporal and spatial characteristics of transient intracellular Ca(2+)-concentration changes in neurons in order to fine-tune the strength and duration of the output signal. CaBPs have been used as neurochemical markers to identify and trace neurons of several brain loci including the mammalian retina. The CaBP content of retinal neurons, however, varies between species and, thus, the results inferred from animal models cannot be utilised directly by clinical ophthalmologists.

The Retinal TNAP.

Accumulating evidence from recent literature underline the important roles of tissue non specific alkaline phosphatase (TNAP) in diverse functions as well as diseases of the nervous system. Exploration of TNAP in well characterized neural circuits such as the retina, might significantly advance our understanding regarding neural TNAP's roles. This chapter reviews the scarce literature as well as our findings on retinal TNAP.

Characterization of connexin36 gap junctions in the human outer retina.

Retinal connexins (Cx) form gap junctions (GJ) in key circuits that transmit average or synchronize signals. Expression of Cx36, -45, -50 and -57 have been described in many species but there is still a disconcerting paucity of information regarding the Cx makeup of human retinal GJs. We used well-preserved human postmortem samples to characterize Cx36 GJ constituent circuits of the outer plexiform layer (OPL).