Dataset Information

Retinal-input-induced epigenetic dynamics in the developing mouse dorsal lateral geniculate nucleus.

ABSTRACT: DNA methylation plays important roles in the regulation of nervous system development and in cellular responses to environmental stimuli such as light-derived signals. Despite great efforts in understanding the maturation and refinement of visual circuits, we lack a clear understanding of how changes in DNA methylation correlate with visual activity in the developing subcortical visual system, such as in the dorsal lateral geniculate nucleus (dLGN), the main retino-recipient region in the dorsal thalamus. Here, we explored epigenetic dynamics underlying dLGN development at ages before and after eye opening in wild-type mice and mutant mice in which retinal ganglion cells fail to form. We observed that development-related epigenetic changes tend to co-localize together on functional genomic regions critical for regulating gene expression, while retinal-input-induced epigenetic changes are enriched on repetitive elements. Enhancers identified in neurons are prone to methylation dynamics during development, and activity-induced enhancers are associated with retinal-input-induced epigenetic changes. Intriguingly, the binding motifs of activity-dependent transcription factors, including EGR1 and members of MEF2 family, are enriched in the genomic regions with epigenetic aberrations in dLGN tissues of mutant mice lacking retinal inputs. Overall, our study sheds new light on the epigenetic regulatory mechanisms underlying the role of retinal inputs on the development of mouse dLGN.

SUBMITTER: He J

PROVIDER: S-EPMC6374911 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Retinal-input-induced epigenetic dynamics in the developing mouse dorsal lateral geniculate nucleus.

He Jianlin J Xu Xiguang X Monavarfeshani Aboozar A Banerjee Sharmi S Fox Michael A MA Xie Hehuang H

Epigenetics & chromatin 20190214 1

DNA methylation plays important roles in the regulation of nervous system development and in cellular responses to environmental stimuli such as light-derived signals. Despite great efforts in understanding the maturation and refinement of visual circuits, we lack a clear understanding of how changes in DNA methylation correlate with visual activity in the developing subcortical visual system, such as in the dorsal lateral geniculate nucleus (dLGN), the main retino-recipient region in the dorsal ...[more]

PMID: 30764861

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Project description:In both dichromats and trichromats, cone opsin signals are maintained independently in cones and combined at the bipolar and retinal ganglion cell level, creating parallel color opponent pathways to the central visual system. Like other dichromats, the mouse retina expresses a short-wavelength (S) and a medium-wavelength (M) opsin, with the S-opsin shifted to peak sensitivity in the ultraviolet (UV) range. Unlike in primates, nonuniform opsin expression across the retina and coexpression in single cones creates a mostly mixed chromatic signal. Here, we describe the visuotopic and chromatic organization of spiking responses in the dorsal lateral geniculate and of the local field potentials in their recipient zone in primary visual cortex (V1). We used an immersive visual stimulus dome that allowed us to present spatiotemporally modulated UV and green luminance in any region of the visual field of an awake, head-fixed mouse. Consistent with retinal expression of opsins, we observed graded UV-to-green dominated responses from the upper to lower visual fields, with a smaller difference across azimuth. In addition, we identified a subpopulation of cells (<10%) that exhibited spectrally opponent responses along the S-M axis. Luminance signals of each wavelength and color signals project to the middle layers of V1.Significance statementIn natural environments, color information is useful for guiding behavior. How small terrestrial mammals such as mice use graded expression of cone opsins to extract visual information from their environments is not clear, even as the use of mice for studying visually guided behavior grows. In this study, we examined the color signals that the retina sends to the visual cortex via the lateral geniculate nucleus of the thalamus. We found that green dominated responses in the lower and nasal visual field and ultraviolet dominated responses in the upper visual field. We describe a subset of cells that exhibit color opponent responses.

Project description:The thalamic reticular nucleus (TRN) is a shell-like structure comprised of GABAergic neurons that surrounds the dorsal thalamus. While playing a key role in modulating thalamocortical interactions, TRN inhibition of thalamic activity is often thought of as having an all-or-none impact. Although TRN neurons have a dynamic firing range, it remains unclear how variable rates of TRN activity gate thalamocortical transmission. To address this, we examined the ultrastructural features and functional synaptic properties of the feedback connections in the mouse thalamus between TRN and the dorsal lateral geniculate nucleus (dLGN), the principal relay of retinal signals to visual cortex. Using electron microscopy to identify TRN input to dLGN, we found that TRN terminals formed synapses with non-GABAergic postsynaptic profiles. Compared with other nonretinal terminals in dLGN, those from TRN were relatively large and tended to contact proximal regions of relay cell dendrites. To evoke TRN activity in dLGN, we adopted an optogenetic approach by expressing ChR2, or a variant (ChIEF) in TRN terminals. Both in vitro and in vivo recordings revealed that repetitive stimulation of TRN terminals led to a frequency-dependent inhibition of dLGN activity, with higher rates of stimulation resulting in increasing levels of membrane hyperpolarization and corresponding decreases in spike firing. This relationship suggests that alterations in TRN activity lead to graded changes in relay cell spike firing.NEW & NOTEWORTHY The thalamic reticular nucleus (TRN) modulates thalamocortical transmission through inhibition. In mouse, TRN terminals in the dorsal lateral geniculate nucleus (dLGN) form synapses with relay neurons but not interneurons. Stimulation of TRN terminals in dLGN leads to a frequency-dependent form of inhibition, with higher rates of stimulation leading to a greater suppression of spike firing. Thus, TRN inhibition appears more dynamic than previously recognized, having a graded rather than an all-or-none impact on thalamocortical transmission.

Dataset Information

Retinal-input-induced epigenetic dynamics in the developing mouse dorsal lateral geniculate nucleus.

Publications

Retinal-input-induced epigenetic dynamics in the developing mouse dorsal lateral geniculate nucleus.

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