Coherent spike activity occurs between widely separated retinal ganglion cells (RGCs) in response to a large, contiguous object, but not to disjointed objects. Since the large spatial separation between the RGCs precludes common excitatory inputs from bipolar cells, the mechanism underlying this long-range coherence remains unclear. Here, we show that electrical coupling between RGCs and polyaxonal amacrine cells in mouse retina forms the synaptic mechanism responsible for long-range coherent activity in the retina. Pharmacological blockade of gap junctions or genetic ablation of connexin 36 (Cx36) subunits eliminates the long-range correlated spiking between RGCs. Moreover, we find that blockade of gap junctions or ablation of Cx36 significantly reduces the ability of mice to discriminate large, global objects from small, disjointed stimuli. Our results indicate that synchronous activity of RGCs, derived from electrical coupling with amacrine cells, encodes information critical to global object perception.
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http://dx.doi.org/10.1073/pnas.1708261114 | DOI Listing |
Unlabelled: Chronic back pain (CBP) is the leading cause of disability affecting 1 in 10 people worldwide. Symptoms are marked by persistent lower back pain, reduced mobility, and heightened cold sensitivity. Here, we utilize a mouse model of CBP induced by injecting urokinase-type plasminogen activator (uPA), a proinflammatory agent in the fibrinolytic pathway, between the L2/L3 lumbar vertebrae.
View Article and Find Full Text PDFNeurons use cell-adhesion molecules (CAMs) to interact with other neurons and the extracellular environment: the combination of CAMs specifies migration patterns, neuronal morphologies, and synaptic connections across diverse neuron types. Yet little is known regarding the intracellular signaling cascade mediating the CAM recognitions at the cell surface across different neuron types. In this study, we investigated the neural developmental role of Afadin , a cytosolic adapter protein that connects multiple CAM families to intracellular F-actin.
View Article and Find Full Text PDFDiverse retinal ganglion cells (RGCs) transmit distinct visual features from the eye to the brain. Recent studies have categorized RGCs into 45 types in mice based on transcriptomic profiles, showing strong alignment with morphological and electrophysiological properties. However, little is known about how these types are spatially arranged on the two-dimensional retinal surface-an organization that influences visual encoding-and how their local microenvironments impact development and neurodegenerative responses.
View Article and Find Full Text PDFActa Neuropathol Commun
January 2025
Ophthalmology, Novartis Biomedical Research, Cambridge, MA, USA.
Neurodegeneration in glaucoma patients is clinically identified through longitudinal assessment of structure-function changes, including intraocular pressure, cup-to-disc ratios from fundus images, and optical coherence tomography imaging of the retinal nerve fiber layer. Use of human post-mortem ocular tissue for basic research is rising in the glaucoma field, yet there are challenges in assessing disease stage and severity, since tissue donations with informed consent are often unaccompanied by detailed pre-mortem clinical information. Further, the interpretation of disease severity based solely on anatomical and morphological assessments by histology can be affected by differences in death-to-preservation time and tissue processing.
View Article and Find Full Text PDFJ Control Release
January 2025
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Institute of Urology, Beijing Municipal Health Commission, Beijing 100050, China. Electronic address:
We previously established an effective method to ameliorate erectile dysfunction (ED) using intracavernous injection (ICI) of mesenchymal stem cell (MSC) microspheres. However, the expression of a key neurotrophic factor, brain-derived neurotrophic factor (BDNF), was low in both MSCs and MSC microspheres, restricting the associated neural repair. Based on the hypoxia and oxidative stress microenvironments within cell spheroids and lesion areas, BDNF-expressing nanocomplexes that are dual-responsive to hypoxia and reactive oxygen species were designed to modify MSCs, achieving high BDNF expression in MSC spheroids.
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