Biology subjects

Lyon, D. C.

Publications and source records attributed to Lyon, D. C..

9 recordsLinked to original sources

bioRxiv2026

Somatotopic Organization of the Ventroposterior Nucleus of the Thalamus in Macaque Monkeys with Dorsal Spinal Cord Injuries Sustained During Early Postnatal Development

Injuries to peripheral nerves or the spinal cord lead to changes in the topographic organization in the brain at multiple levels along the sensory pathways. In adult monkeys large-scale deafferentations due to transection of the dorsal columns of the spinal cord at cervical levels result in large-scale reorganizations such that the deafferented neurons in the hand representation of somatosensory cortical area 3b start responding to anatomically distant body parts such as the chin. However, reorganization following dorsal column injuries depends upon the age at the time of the injury. The somatotopy of areas 3b, 1 and 2 in macaque monkeys with injuries sustained on or before postnatal day (PND) 5 is very normal-like. Whereas in monkeys with injuries sustained between PND9 and PND12, a large extent of the deafferented somatosensory cortex remains unresponsive to peripheral touch, with neurons at only a few sites responding to touch on the face or arm. Here we determined the organization of the ventroposterior nucleus (VPN) of the thalamus in four of these monkeys (Macaca radiata, 3 females, 1 male) that received lesions of the dorsal columns on PND 3, 5 and 9. We show that the nature of reorganization of VPN largely resembles that of the somatosensory cortex. Somatotopy is normal-like after lesions on PND3 and 5, whereas after lesion on PND9, the deprived neurons are largely unresponsive to peripheral touch, with a limited expansion of the chin representation.

neuroscience↗

bioRxiv2025

Restoration of Higher-Order Cortical Processing in Rat V2 by Retinal Sheet Transplants in Degenerated Rats

Age-related macular degeneration (AMD) is a leading cause of central vision loss, and effective treatment options are limited once photoreceptors and the retinal pigment epithelium (RPE) are lost. In advanced stages, vision restoration requires strategies that replace or bypass degenerated retinal circuitry. Retinal sheet transplantation using fetal neural retinal tissue has emerged as a promising intervention, demonstrating long-term survival, integration with the host retina, and partial restoration of light-driven responses. We previously showed that such transplants can restore fundamental visual response properties in the primary visual cortex (V1) of rapidly degenerating rats. However, it remains unclear whether restored retinal input can support higher-order cortical computations that depend on the integration of classical and extra-classical receptive field mechanisms. In this study, we extend this investigation by evaluating whether fetal retinal sheet transplants can restore extra-classical surround modulation in neurons of higher visual areas (V2). Fetal retinal sheets (E18-E19) derived from donor rats were transplanted into one eye of Rho-S334ter line-3 rats at ages P41-P78, when rod degeneration is nearly complete and cones are largely nonfunctional. Animals were assessed 2.2-9.3 months post-surgery using in vivo extracellular single-unit recordings from V2, optokinetic testing, OCT imaging, and histology. Control groups included normal-vision rats, age-matched degenerated rats (AMC), and sham-operated line-3 rats. Transplants survived long term, developed laminated and rosetted photoreceptor structures, and integrated with the host retina. Optokinetic testing revealed significant improvement in spatial acuity in transplanted eyes compared with degenerated controls beginning at three months post-surgery. Transplanted rats exhibited a markedly higher proportion of visually responsive V2 neurons than degenerated animals (21.0% vs. 8.2%). They also showed significantly shorter response latencies and larger visually evoked response amplitudes, indicating improved transmission of retinal signals to the cortex. To quantify surround suppression, neurons were tested with sinusoidal gratings confined to the classical receptive field and gratings extended to full-field size. Transplanted rats displayed robust surround suppression properties similar to normal controls, including significantly reduced firing rates and narrower tuning under full-field conditions. A Support Vector Machine (SVM) classifier trained on net responses to CRF and FF stimulus sizes reliably distinguished control and transplanted neurons from degenerated ones but could not separate control from transplant, further indicating similar response properties in these two groups. These findings provide the first demonstration that retinal sheet transplants restore not only basic visual responses but also higher-order cortical mechanisms involving extra-classical surround suppression. This recovery of surround suppression in V2 suggests that transplanted retinal tissue can re-establish functionally meaningful circuits capable of supporting complex visual processing. The results underscore the therapeutic potential of retinal sheet transplantation for advanced retinal degenerative disease and provide the first evidence of surround suppression in the rat V2.

neuroscience↗

bioRxiv2024

Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Reversing Age-related Vision Decline

The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD). ELOVL2 (Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently the best predictor of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2C234W) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals significantly improved visual function and reduced accumulation of ApoE, HTRA1 and complement proteins in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature of younger retina. Finally, we present the first human genetic data showing significant association of several variants in the human ELOVL2 locus with the onset of intermediate AMD, underlying the translational significance of our findings. In sum, our study identifies novel therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.

molecular biology↗

bioRxiv2022

Visual system hyperexcitability and compromised V1 receptive field properties in early-stage retinitis pigmentosa in mice

Inherited retinal degenerative diseases are a prominent cause of blindness. Even though mutations causing death of photoreceptors are mostly known, the pathophysiology downstream in the inner retina and along the visual pathway is incompletely characterized in the earliest disease stages. Here we investigated retinal, midbrain and cortical visual function using electroretinography (ERG), the optomotor response (OMR), visual evoked potentials (VEPs), respectively, and single unit electrophysiology at the primary visual cortex (V1) in light-adapted juvenile ([~] 1-month-old) and young adult (3-month-old) RhoP23H/WT mice, representative of early-stage retinitis pigmentosa (RP). Photopic ERG revealed up to [~] 30 % hypersensitivity to light in RhoP23H/WT mice, as measured by the light intensity required to generate half-maximal b-wave (I50 parameter). RhoP23H/WT mice also showed increased optomotor responses towards low spatial frequency drifting gratings, indicative of visual overexcitation at the midbrain level. At the V1 level, VEPs and single-cell recordings revealed prominent hyperexcitability in the juvenile RhoP23H/WT mice. Mean VEP amplitudes for light ON stimuli were nearly doubled in 1-month-old RhoP23H/WT mice compared to controls, and more than doubled for light OFF. Single-cell recordings showed a significantly increased spontaneous V1 neuron firing in the RhoP23H/WT mice, and persistent contrast and temporal sensitivities. In contrast, direction selectivity was severely compromised. Our data suggest that during early RP, the visual pathway becomes hyperexcited. This could have both compensatory and deleterious consequences for visual behavior. Further studies on the mechanisms of hyperexcitability are warranted as this could lead to therapeutic interventions for RP. Significance statementLost retinal function in many blinding retinal degenerative disorders could soon be alleviated by advanced therapies that restore photoreception. However, it is unknown whether a visual system rewired downstream of the photoreceptors can process signals adequately. We studied the functional consequences of early rod death along the visual pathway in young retinitis pigmentosa (RP) mice. Photopic inner retina responses were moderately hypersensitized in the electroretinograms of RP mice. Reflex-based visual behavior and visual cortex electrophysiology showed hyperexcitability. Some aspects of complex visual processing were remarkably resistant to degeneration, whereas others were severely impacted. We conclude that the visual system adapts to lost photoreception by increasing sensitivity, but simultaneously becomes detrimentally hyperexcited. Mechanistic understanding could lead to therapeutic preservation and restoration of vision.

physiology↗

bioRxiv2022

Accelerated aging induced by stress in experimental murine ocular hypertension.

Aging, a universal process that affects all cells in an organism, is a major risk factor for a group of neuropathies called glaucoma, where elevated intraocular pressure is one of the known stresses affecting the tissue. Our understanding of molecular impact of aging on response to stress in retina is very limited, therefore we developed a new mouse model to approach this question experimentally. Here we show that susceptibility to response to stress increases with age and is primed on epigenetic level. We demonstrate that program activated by hypertension is similar to natural aging, and that one of the earliest pathways activated upon stress is senescence. Finally, we show that multiple instances of pressure elevation cause accelerated aging of young retina as measured on transcriptional and epigenetic level. Our work emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related eye-diseases, including glaucoma.

molecular biology↗

bioRxiv2020

Primary visual cortex injury produces loss of inhibitory neurons and long-term visual circuit dysfunction

Primary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effect of traumatic brain injury on visual system function. Here we applied a mild focal contusion injury to primary visual cortex (V1) in adult mice. We found that, although V1 was largely intact in brain-injured mice, there was a reduction in the number of inhibitory interneurons that extended into deep cortical layers. In general, we found a preferential reduction of interneurons located in superficial layers, near the impact site, while interneurons positioned in deeper layers were better preserved. Three months after injury, V1 neurons showed dramatically reduced responses to visual stimuli and weaker orientation selectivity and tuning, consistent with the loss of cortical inhibition. Our results demonstrate that V1 neurons no longer robustly and stably encode visual input following a mild traumatic injury. HighlightsO_LIInhibitory neurons are lost throughout brain injured visual cortex C_LIO_LIVisually-evoked potentials are severely degraded after injury C_LIO_LIInjured V1 neurons show weaker selectivity and tuning consistent with reduced interneurons C_LI

neuroscience↗

bioRxiv2020

Novel rabies virus variant for bi-directional optical control reveals modulatory influence of the pulvinar on visual cortex in rat

Optogenetic tools have become of great utility in the causal analysis of systems in the brain. However, current optogenetic techniques do not reliably support both excitation and suppression of the same cells in vivo, limiting analysis and slowing research. Here we developed a novel glycoprotein-deleted rabies virus expressing two channelrhodopsin proteins, GtACR2 and Chrimson, in order to independently manipulate excitatory and inhibitory transmembrane potentials, respectively. Using this approach, we demonstrated that rodent pulvinar neurons modulate cortical size tuning and suppress flash responses, but do not drive activity in visual cortex. While our goal was primarily to develop this novel method to study the structure-function organization of thalamocortical circuits, this technique is readily applicable to study any brain region.

neuroscience↗

bioRxiv2020

Projections between visual cortex and pulvinar nucleus in the rat

The extrageniculate visual pathway, which carries visual information from the retina through the superficial layers of the superior colliculus and the pulvinar nucleus, is poorly understood. The pulvinar is thought to modulate information flow between cortical areas, and has been implicated in cognitive tasks like directing visually guided actions. In order to better understand the underlying circuitry, we performed retrograde injections of modified rabies virus in the visual cortex and pulvinar of the Long-Evans rat. We found a relatively small population of cells projecting to primary visual cortex (V1), compared to a much larger population projecting to higher visual cortex. Reciprocal corticothalamic projections showed a similar result, implying that pulvinar does not play as big a role in directly modulating V1 activity as previously thought.

neuroscience↗

bioRxiv2020

Visual response characteristics in lateral and medial subdivisions of the rat pulvinar

The pulvinar is a higher-order thalamic relay and a central component of the extrageniculate visual pathway, with input from the superior colliculus and visual cortex and output to all of visual cortex. Rodent pulvinar, more commonly called the lateral posterior nucleus (LP), consists of three highly-conserved subdivisions, and offers the advantage of simplicity in its study compared to more subdivided primate pulvinar. Little is known about receptive field properties of LP, let alone whether functional differences exist between different LP subdivisions, making it difficult to understand what visual information is relayed and what kinds of computations the pulvinar might support. Here, we characterized single-cell response properties in two V1 recipient subdivisions of rat pulvinar, the rostromedial (LPrm) and lateral (LPl), and found that a fourth of the cells were selective for orientation, compared to half in V1, and that LP tuning widths were significantly broader. Response latencies were also significantly longer and preferred size more than three times larger on average than in V1; the latter suggesting pulvinar as a source of spatial context to V1. Between subdivisons, LPl cells preferred higher temporal frequencies, whereas LPrm showed a greater degree of direction selectivity and pattern motion detection. Taken together with known differences in connectivity patterns, these results suggest two separate visual feature processing channels in the pulvinar, one in LPl related to higher speed processing which likely derives from superior colliculus input, and the other in LPrm for motion processing derived through input from visual cortex. Significance StatementThe pulvinar has a perplexing role in visual cognition as no clear link has been found between the functional properties of its neurons and behavioral deficits that arise when it is damaged. The pulvinar, called the lateral posterior nucleus (LP) in rats, is a higher order thalamic relay with input from the superior colliculus and visual cortex and output to all of visual cortex. By characterizing single-cell response properties in anatomically distinct subdivisions we found two separate visual feature processing channels in the pulvinar, one in lateral LP related to higher speed processing which likely derives from superior colliculus input, and the other in rostromedial LP for motion processing derived through input from visual cortex.

neuroscience↗