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Dye, L.

Publications and source records attributed to Dye, L..

4 recordsLinked to original sources

Visual deprivation in adulthood engages presynaptic plasticity of thalamocortical synapses

Synaptic plasticity between neurons in first order thalamus and layer 4 cortex is greatest during an early postnatal critical period and was thought to decrease irreversibly with age. However, here we show that robust and reversible plasticity can be induced in adult mice at synapses between dLGN axons and visual cortex layer 4 neurons by prolonged dark exposure (DE) and light reintroduction (LRx). Unexpectedly, the experience-dependent change in synaptic strength was mediated by a change in presynaptic structure, organization and function. DE/LRx declusters/clusters synaptic vesicles and reorganizes presynaptic molecular geometry. Furthermore, DE/LRx decreases/increases visually-evoked and spontaneous calcium signaling and neurotransmitter release probability in dLGN axonal boutons. The presynaptic plasticity mechanism described here has a high threshold for engagement which would allow maintenance of synapse stability across a wide activity range, and reactivation of thalamocortical plasticity in extraordinary conditions.

neuroscience↗

RNase H1 levels dramatically affect mitochondrial genome maintenance with little impact on nuclear R-loops in murine B cells

Overexpression of RNase H1, a ribonuclease that degrades RNA:DNA hybrids and R-loops, can suppress genome instability phenotypes in a range of maladaptive conditions. This has been interpreted to suggest that genotoxic co-transcriptional R-loops arise under these conditions and are resolved by RNase H1. Here, we manipulated RNase H1 levels using conditional knockout and overexpression models in primary murine B cells and mapped the resulting genomic R-loop landscapes. Rnaseh1 deletion resulted in a dramatic loss of mitochondrial replication and compromised B cell responses, consistent with a critical mitochondrial function for RNase H1. Genome-wide R-loops were, however, not significantly affected. More surprisingly, overexpressing active nuclear RNase H1 did not lead to significant reduction of R-loop levels or change their distribution. These results were confirmed using a human cell line in which active, nuclear RNase H1 can be induced. Our findings indicate that co-transcriptional R-loops are not efficiently resolved by RNase H1 and suggest that the identity of the RNA/DNA hybrids at the root of the genome instability phenotypes suppressed by RNase H1 may need to be re-interpreted.

genomics↗

Adult visual deprivation engages associative, presynaptic plasticity of thalamic input to cortex

Age constrains plasticity at inputs from first order thalamic nuclei to the cortex, endowing stability to ascending, feed-forward projections. However, here we show that prolonged visual deprivation can induce robust and reversible plasticity at thalamocortical synapses in layer 4 pyramidal neurons in the adult mouse primary visual cortex. The plasticity engaged by prolonged visual deprivation is non-homeostatic and mediated by changes in presynaptic function.

neuroscience↗

The axillary lymphoid organ - an external, experimentally accessible immune organ in the zebrafish

Lymph nodes and other secondary lymphoid organs play critical roles in immune surveillance and immune activation in mammals, but the deep internal locations of these organs make it challenging to image and study them in living animals. Here, we describe a previously uncharacterized external immune organ in the zebrafish ideally suited for studying immune cell dynamics in vivo, the axillary lymphoid organ (ALO). This small, translucent organ has an outer cortex teeming with immune cells, an inner medulla with a mesh-like network of fibroblastic reticular cells along which immune cells migrate, and a network of lymphatic vessels draining to a large adjacent lymph sac. Noninvasive high-resolution imaging of transgenically marked immune cells can be carried out in the lobes of living animals, and the ALO is readily accessible to external treatment. This newly discovered tissue provides a superb model for dynamic live imaging of immune cells and their interaction with pathogens and surrounding tissues, including blood and lymphatic vessels. TeaserA newly characterized external zebrafish lymphoid organ provides a powerful model for live imaging of immune cell dynamics

developmental biology↗