ABSTRACT
Enabling near-infrared light sensitivity in a blind human retina may supplement or restore visual function in patients with regional retinal degeneration. We induced near-infrared light sensitivity using gold nanorods bound to temperature-sensitive engineered transient receptor potential (TRP) channels. We expressed mammalian or snake TRP channels in light-insensitive retinal cones in a mouse model of retinal degeneration. Near-infrared stimulation increased activity in cones, ganglion cell layer neurons, and cortical neurons, and enabled mice to perform a learned light-driven behavior. We tuned responses to different wavelengths, by using nanorods of different lengths, and to different radiant powers, by using engineered channels with different temperature thresholds. We targeted TRP channels to human retinas, which allowed the postmortem activation of different cell types by near-infrared light.
Subject(s)
Blindness/therapy , Gold , Infrared Rays , Nanotubes , Retinal Degeneration/therapy , Sensory Thresholds/radiation effects , TRPC Cation Channels/physiology , Vision, Ocular/radiation effects , Animals , Blindness/physiopathology , Disease Models, Animal , Evoked Potentials, Visual/physiology , Evoked Potentials, Visual/radiation effects , Genetic Engineering , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL , Photic Stimulation , Rats , Retinal Cone Photoreceptor Cells/physiology , Retinal Cone Photoreceptor Cells/radiation effects , Retinal Degeneration/physiopathology , Retinal Ganglion Cells/physiology , Retinal Ganglion Cells/radiation effects , Sensory Thresholds/physiology , Snakes , TRPC Cation Channels/genetics , TRPV Cation Channels/genetics , TRPV Cation Channels/physiology , Vision, Ocular/physiology , Visual Cortex/physiopathology , Visual Cortex/radiation effectsABSTRACT
How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity, either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells, and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an over-representation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the over-representation of posterior-motion-preferring cortical cells disappeared, and their responses at higher stimulus speeds were reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex.
Subject(s)
Amacrine Cells/physiology , Motion Perception/physiology , Retina/physiology , Visual Cortex/physiology , Animals , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Diphtheria Toxin/pharmacology , Female , Male , Mice , Mice, Knockout , Mice, Transgenic , Photic Stimulation , Retina/drug effects , Retina/metabolism , Visual Cortex/metabolism , Visual Pathways/physiologyABSTRACT
Individual cortical neurons can selectively respond to specific environmental features, such as visual motion or faces. How this relates to the selectivity of the presynaptic network across cortical layers remains unclear. We used single-cell-initiated, monosynaptically restricted retrograde transsynaptic tracing with rabies viruses expressing GCaMP6s to image, in vivo, the visual motion-evoked activity of individual layer 2/3 pyramidal neurons and their presynaptic networks across layers in mouse primary visual cortex. Neurons within each layer exhibited similar motion direction preferences, forming layer-specific functional modules. In one-third of the networks, the layer modules were locked to the direction preference of the postsynaptic neuron, whereas for other networks the direction preference varied by layer. Thus, there exist feature-locked and feature-variant cortical networks.
Subject(s)
Presynaptic Terminals/physiology , Pyramidal Cells/physiology , Visual Cortex/physiology , Animals , Calcium-Binding Proteins/chemistry , Calcium-Binding Proteins/genetics , Evoked Potentials, Visual , Luminescent Proteins/chemistry , Luminescent Proteins/genetics , Mice , Motion , Nerve Net/cytology , Nerve Net/physiology , Neuroimaging , Rabies virus , Single-Cell AnalysisABSTRACT
Vertebrate vision relies on two types of photoreceptors, rods and cones, which signal increments in light intensity with graded hyperpolarizations. Rods operate in the lower range of light intensities while cones operate at brighter intensities. The receptive fields of both photoreceptors exhibit antagonistic center-surround organization. Here we show that at bright light levels, mouse rods act as relay cells for cone-driven horizontal cell-mediated surround inhibition. In response to large, bright stimuli that activate their surrounds, rods depolarize. Rod depolarization increases with stimulus size, and its action spectrum matches that of cones. Rod responses at high light levels are abolished in mice with nonfunctional cones and when horizontal cells are reversibly inactivated. Rod depolarization is conveyed to the inner retina via postsynaptic circuit elements, namely the rod bipolar cells. Our results show that the retinal circuitry repurposes rods, when they are not directly sensing light, to relay cone-driven surround inhibition.
