Abstract A novel class of photoreceptors, the intrinsically photosensitive retinal ganglion cells (ipRGCs), express photopigment melanopsin and drive non‐image‐forming responses to light such as circadian photoentrainment, pupillary reflex suppression nocturnal melatonin production in pineal. Because dendrites from one subclass these – M1‐type ipRGCs make presumptive synaptic contacts at sites dopamine release dopaminergic amacrine cells, they are prime targets for modulation by dopamine, a...

Abstract Glaucoma is a complex group of diseases wherein selective degeneration retinal ganglion cells (RGCs) lead to irreversible loss vision. A comprehensive approach glaucomatous RGC may include stem functionally replace dead neurons through transplantation and understand RGCs vulnerability using disease in dish cell model. Both approaches require the directed generation stable, functional, target-specific from renewable sources cells, that is, embryonic induced pluripotent cells. Here,...

Numerous neuronal properties including the synaptic vesicle release process, neurotransmitter receptor complement, and postsynaptic ion channels are involved in transforming inputs into spiking. Temperature is a significant influencer of function integration. Changing temperature can affect physiology diversity ways depending on how it affects different members cell's channel complement. Temperature's effects critical for pathological states such as fever, which trigger seizure activity, but...

Vesicle release from rod photoreceptors is regulated by Ca(2+) entry through L-type channels located near synaptic ribbons. We characterized sites and kinetics of vesicle in salamander rods using total internal reflection fluorescence microscopy to visualize fusion individual vesicles. A small number vesicles were loaded brief incubation with FM1-43 or a dextran-conjugated, pH-sensitive form rhodamine, pHrodo. Labeled organelles matched the diffraction-limited size fluorescent microspheres...

Abstract Glaucoma represents a group of multifactorial diseases with unifying pathology progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an vitro model using SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, demonstrate efficiency RGC generation by iPSCs is significantly lower than...

The poor axon regeneration in the central nervous system (CNS) often leads to permanent functional deficit following disease or injury. For example, degeneration of retinal ganglion cell (RGC) axons glaucoma irreversible loss vision. Here, we have tested hypothesis that mTOR pathway regulates development human RGCs and its recruitment after injury facilitates regeneration. We observed is active during RGC differentiation, using induced pluripotent stem model neurogenesis show it function...

Key points In the vertebrate retina, photoreceptors influence signalling of neighbouring through lateral‐inhibitory interactions mediated by horizontal cells (HCs). These create antagonistic centre‐surround receptive fields important for detecting edges and generating chromatically opponent responses in colour vision. The mechanisms responsible inhibitory feedback from HCs involve changes synaptic cleft pH that modulate photoreceptor calcium currents. However, sources protons involved their...

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles that lead to decreased quality life due behavioral, motor, cognitive impairments. Due widespread pathological nature AD, many brain regions are affected Aβ including important for vision such as lateral geniculate nucleus (LGN) thalamus which critical relaying signals from retina primary visual cortex. Using wide range techniques...

Homeostatic plasticity plays important role in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early is altered inputs retinal ganglion cells (RGCs), changes RGC excitability, deficits optic nerve transport energy metabolism. These functional can precede degeneration are likely alter outputs their target...

Juvenile-onset autosomal dominant Stargardt-like macular dystrophy (STGD3) is caused by mutations in ELOVL4 (elongation of very long fatty acids-4), an elongase necessary for the biosynthesis chain acids (VLC-FAs ≥ C26). Photoreceptors are enriched with VLC polyunsaturated (VLC-PUFAs), which long-term survival rod photoreceptors. The purpose these studies was to determine effect deletion VLC-PUFAs on synaptic function retinas mice conditionally depleted (KO) Elovl4.Retina assessed wild-type...

At the first synapse in vertebrate visual pathway, light-evoked changes photoreceptor membrane potential alter rate of glutamate release onto second-order retinal neurons. This process depends on synaptic ribbon, a specialized structure found at various sensory synapses, to provide supply primed vesicles for release. Calcium (Ca2+) accelerates replenishment cone ribbon but mechanisms underlying this acceleration and its functional implications vision are unknown. We studied vesicle using...

Axonopathy is a hallmark of many neurodegenerative diseases including glaucoma, where elevated intraocular pressure (ocular hypertension, OHT) stresses retinal ganglion cell (RGC) axons as they exit the eye and form optic nerve. OHT causes early changes in nerve such axon atrophy, transport inhibition, gliosis. Importantly, these appear to occur prior irreversible neuronal loss, making them promising points for diagnosis glaucoma. It unknown whether has similarly effects on function RGC...

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and serve as primary drivers of non-image-forming visual functions such circadian photoentrainment, pupillary light reflex, suppression melatonin production in pineal. Past electrophysiological studies these have focused on their intrinsic photosensitivity synaptic inputs. Much less is known about voltage-gated channels how might shape output to centers. Here, we show that rat ipRGCs retrolabeled...

Following synaptic vesicle exocytosis, neurons retrieve the fused membrane by a process of endocytosis to provide supply vesicles for subsequent release and maintain presynaptic active zone. Rod cone photoreceptors use specialized structure called ribbon that enables them sustain high rates neurotransmitter release. They must also employ mechanisms capable keeping up with While much is known about at another retinal synapse, goldfish Mb1 bipolar cell, less in photoreceptors. We used...

Synaptic communication requires proper coupling between voltage-gated Ca 2+ (Ca V ) channels and synaptic vesicles. In photoreceptors, L-type are clustered close to ribbon release sites. Although clustered, move continuously within a confined domain slightly larger than the base of ribbon. We hypothesized that expanding channel confinement domains should increase number openings needed trigger vesicle release. Using single-particle tracking techniques, we measured expansion caused by...

One of the central tasks in retinal neuroscience is to understand circuitry neurons and how those connections are responsible for shaping signals transmitted brain. Photons detected retina by rod cone photoreceptors, which convert that energy into an electrical signal, transmitting it other neurons, where processed communicated targets brain via optic nerve. Important early insights visual processing came from histological studies Cajal and, later, electrophysiological recordings spiking...

Photoreceptors have depolarized resting potentials that stimulate calcium-dependent release continuously from a large vesicle pool but neurons can also vesicles without stimulation. We characterized the Ca(2+) dependence, pools, and sites involved in spontaneous at photoreceptor ribbon synapses. In whole-cell recordings light-adapted horizontal cells (HCs) of tiger salamander retina, we detected miniature excitatory post-synaptic currents (mEPSCs) when no stimulation was applied to promote...

Inhibitory feedback from horizontal cells (HCs) to cones generates center-surround receptive fields and color opponency in the retina. Mechanisms of HC remain unsettled, but one hypothesis proposes that an ephaptic mechanism may alter extracellular electrical field surrounding photoreceptor synaptic terminals, thereby altering Ca 2+ channel activity output. An voltage change produced by current flowing through open channels membrane should occur with no delay. To test for this mechanism, we...

In addition to vesicle release at synaptic ribbons, rod photoreceptors are capable of substantial slow non-ribbon sites triggered by Ca²⁺-induced Ca²⁺ (CICR) from intracellular stores. To maintain CICR as rods remain depolarized in darkness, we hypothesized that released into the cytoplasm terminal endoplasmic reticulum (ER) can be replenished continuously ions diffusing within ER soma. We measured [Ca²⁺] changes and <i>Ambystoma tigrinum</i> retina using...

Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect utero postnatal exposure on neurodevelopment subsequent behavioral outcomes. Methods: Using preclinical rodent model that mimics oxy (IUO) postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance...

Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of retina called retinal ganglion cells (RGCs). This leads to loss RGC signaling visual centers brain such as dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information cortex conscious vision. In response altered levels activity or synaptic input, can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them scale their responses stabilize...