Machine-guided design of cell-type-targeting cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing and stimulus responses, which collectively define the thousands of unique cell types in the body. While there is great potential for strategically incorporating CREs in therapeutic or biotechnology applications that require tissue specificity, there is no guarantee that an optimal CRE for these intended purposes has arisen naturally. Here we present a platform to engineer and validate synthetic CREs capable of driving gene expression with programmed cell-type specificity.

The Excessive Tonic Inhibition of the Peri-infarct Cortex Depresses Low Gamma Rhythm Power During Poststroke Recovery.

The cortex immediately surrounding a brain ischemic lesion, the peri-infarct cortex (PIC), harbors a large part of the potential to recover lost functions. However, our understanding of the neurophysiological conditions in which synaptic plasticity operates remains limited. Here we hypothesized that the chronic imbalance between excitation and inhibition of the PIC prevents the normalization of the gamma rhythm, a waveband of neural oscillations thought to orchestrate action potential trafficking.

Vascular Response to Spreading Depolarization Predicts Stroke Outcome.

Background: Cortical spreading depolarization (CSD) is a massive neuro-glial depolarization wave, which propagates across the cerebral cortex. In stroke, CSD is a necessary and ubiquitous mechanism for the development of neuronal lesions that initiates in the ischemic core and propagates through the penumbra extending the tissue injury. Although CSD propagation induces dramatic changes in cerebral blood flow, the vascular responses in different ischemic regions and their consequences on reperfusion and recovery remain to be defined.

Prolonged deficit of low gamma oscillations in the peri-infarct cortex of mice after stroke.

Days and weeks after an ischemic stroke, the peri-infarct area adjacent to the necrotic tissue exhibits very intense synaptic reorganization aimed at regaining lost functions. In order to enhance functional recovery, it is important to understand the mechanisms supporting neural repair and neuroplasticity in the cortex surrounding the lesion. Brain oscillations of the local field potential (LFP) are rhythmic fluctuations of neuronal excitability that synchronize neuronal activity to organize information processing and plasticity.