Biology subjects

Park, E. H.

Publications and source records attributed to Park, E. H..

4 recordsLinked to original sources

bioRxiv2024

Escalation of genome defense capacity enables control of an expanding meiotic driver

SummaryFrom RNA interference to chromatin silencing, diverse genome defense pathways silence selfish genetic elements to safeguard genome integrity1,2. Despite their diversity, different defense pathways share a modular organization, where numerous specificity factors identify diverse targets and common effectors silence them. In the PIWI-interacting RNA (piRNA) pathway, which controls selfish elements in the metazoan germline, diverse target RNAs are first identified by complementary base pairing with piRNAs and then silenced by PIWI-clade nucleases via enzymatic cleavage1,3. Such a binary architecture allows the defense systems to be readily adaptable, where new targets can be captured via the innovation of new specificity factors4,5. Thus, our current understanding of genome defense against lineage-specific selfish genes has been largely limited to the evolution of specificity factors, while it remains poorly understood whether other types of innovations are required. Here, we describe a new type of innovation, which escalates the defense capacity of the piRNA pathway to control a recently expanded selfish gene in Drosophila melanogaster. Through an in vivo RNAi screen for repressors of Stellate--a recently evolved and expanded selfish meiotic driver6-8--we discovered a novel defense factor, Trailblazer. Trailblazer is a transcription factor that promotes the expression of two PIWI-clade nucleases, Aub and AGO3, to match Stellate in abundance. Recent innovation in the DNA-binding domain of Trailblazer enabled it to drastically elevate Aub and AGO3 expression in the D. melanogaster lineage, thereby escalating the silencing capacity of the piRNA pathway to control expanded Stellate and safeguard fertility. As copy-number expansion is a recurrent feature of diverse selfish genes across the tree of life9-12, we envision that augmenting the defense capacity to quantitatively match selfish genes is likely a repeatedly employed defense strategy in evolution.

genetics↗

bioRxiv2021

A neuronal code for space in hippocampal coactivity dynamics independent of place fields

Hippocampus is comprised of [~]20% place cells, discharging in cell-specific locations ("place fields"), standardly interpreted as a dedicated neuronal code for space. However, place cell discharge is temporally unreliable across seconds and days, and place fields are multimodal, suggesting an alternative "ensemble cofiring" spatial code with manifold dynamics that does not require reliable spatial tuning. We evaluated these hypotheses using GCaMP6f and miniature microscopes to image mouse CA1 ensemble activity in two environments, across 3 weeks. Both place fields and ensemble coactivity relationships appear to "remap," being distinct between, and (weakly) similar within environments. Decoding location as well as environment from 1-s ensemble location-specific discharge is effective and improves with experience. Decoding the environment (but not location) from cell-pair coactivity relationships is also effective and improves with experience, even after removing place tuning. Discriminating environments from 1-s ensemble coactivity relies crucially on the cells with the most anti-cofiring cell-pair relationships because ensemble activity is internally-organized on a low-dimensional manifold of non-linear cofiring relationships that intermittently reregisters to environments according to the anti-cofiring subpopulation activity.

neuroscience↗

bioRxiv2020

Dentate spikes and external control of hippocampal function

Mouse hippocampus CA1 place-cell discharge typically encodes current location but during slow gamma dominance (SGdom), when slow gamma oscillations (30-50 Hz) dominate mid-frequency gamma oscillations (70-90 Hz) in CA1 local field potentials, CA1 discharge switches to represent distant recollected locations. We report that dentate spike type 2 (DSM) events initiated by MECII[->]DG inputs promote SGdom and change excitation-inhibition coordinated discharge in DG, CA3, and CA1, whereas type 1 (DSL) events initiated by LECII[->]DG inputs do not. Just before SGdom, LECII-originating slow gamma oscillations in dentate gyrus and CA3-originating slow gamma oscillations in CA1 phase and frequency synchronize at the DSM peak when discharge within DG and CA3 increases to promote excitation-inhibition cofiring within and across the DG[->]CA3[->]CA1 pathway. This optimizes discharge for the 5-10 ms DG-to-CA1 neuro-transmission that coincides with SGdom. DSM properties identify extrahippocampal control of SGdom, and a cortico-hippocampal mechanism that switches between memory-related modes of information processing.

neuroscience↗

bioRxiv2019

Is the rat prefrontal cortex crucial for cognitive control during spatial cognition?

Cognitive control tasks require using one class of information while ignoring competing classes of information. The central role of the medial prefrontal cortex (mPFC) in cognitive control is well established in the primate literature, and largely accepted in the rodent literature because mPFC damage causes deficits in tasks that may require cognitive control, as inferred, typically from the task design. In prior work, we used an active place avoidance task where a rat or mouse on a rotating arena is required to avoid the stationary task-relevant locations of a mild shock and ignore the rotating task-irrelevant locations of those shocks. The task is impaired by hippocampal manipulations, and the discharge of hippocampal place cell populations judiciously alternates between representing stationary locations near the shock zone and rotating locations far from the shock zone, demonstrating cognitive control concurrently in behavior and the hippocampal representation of spatial information. Here we test whether rat mPFC lesion impairs the active place avoidance task to evaluate two competing hypotheses, a "central-computation" hypothesis that the mPFC is essential for the computations required for cognitive control and an alternative "local-computation" hypothesis that other brain areas can perform the computations required for cognitive control, independent of mPFC. Ibotenic acid lesion of the mPFC was effective, damaging the cingulate, prelimbic and infralimbic cortices. The lesion also altered the normal coordination of metabolic activity across remaining structures. The lesion did not impair learning to avoid the initial location of shock or long-term place avoidance memory, but impaired avoidance after the shock was relocated. The lesion also did not impair the alternation between task-relevant and task-irrelevant hippocampal representations of place information. These findings support the local-computation hypothesis that computations required for cognitive control can occur locally in brain networks independently of the mPFC.

neuroscience↗