The reestablishment of functional neural networks is vital to stroke recovery and readily occurs during the post-stroke critical period: a window of heightened neuroplasticity and training sensitivity. Although evidence suggests that neural repair processes are engaged as a part of the obligate response to stroke, the mechanisms of these processes remain unknown. Here, using widefield and 2-photon calcium imaging of awake, behaving mice, we determined that surviving neurons in the perilesional tissue are inactive after stroke. These neurons adapt to this prolonged inactivity after stroke by modifying excitatory synapses to include more NR2B-containing NMDA receptors. The inactivity-mediated increase in NR2B expression is critical for recovery since NR2B antagonism or chemogenetic activation prevents recovery. We extend this logic byalso demonstrating demonstrate that experimental neuronal inactivation can restore the post-stroke critical period in a NR2B-dependent manner. Together, our results identify a novel potential stroke therapy and provide a conceptual framework for post-stroke plasticity and functional recovery.

Apoptosis is a highly conserved form of programmed cell death in multicellular organisms where a cell activates caspase proteases to trigger its own demise. It has critical functions under physiological conditions in removing superfluous or damaged cells from a healthy organism. However, dysregulated apoptosis plays an important role in diseases: improper or elevated apoptosis leads to diseases of cell loss, such as diabetes or neurodegeneration, while deficiencies in apoptosis can contribute to tumor cell growth and survival.

While the importance of apoptosis during late embryogenesis is well-established, its function during the earliest stages of development, namely the exit of embryonic stem cells (ESC) from the pluripotent state, is unclear. Here, I discovered that apoptosis plays a critical role in removing slow-differentiating murine ESC from the total cell population. This is initiated by p53-dependent upregulation of the Fas death receptor on straggling ESCs, which then triggers apoptosis specifically in these cells. An inability to initiate apoptosis, by transient knockdown or genetic deletion of components of this pathway, causes retention of slow-differentiating ESCs and a global delay in differentiation, both in vitro and in an in vivo teratoma model. Thus, apoptosis is crucial in promoting the efficient differentiation of ESCs.

While apoptosis is important for normal development, elevated levels due to cellular stress can cause inappropriate cell loss and degeneration, leading to disease. One such example is retinitis pigmentosa, an inherited disease where rod photoreceptors are progressively lost from the neural retina, eventually leading to blindness. There is increasing evidence that accumulation of unfolded proteins within the endoplasmic reticulum (ER) of rod photoreceptors causes ER stress and subsequent cell death. Here, I utilize a novel small molecule inhibitor to show that inhibition of IRE1α, an ER transmembrane kinase/endoribonuclease that can signal both adaptation and apoptosis in response to ER stress, preserves rod photoreceptor viability and function in two rodent models of ER stress-induced photoreceptor degeneration.

These findings reveal new insights into the role of apoptosis under both normal and stressed conditions, and may have implications for human diseases such as cancer and neurodegeneration.

Stationary and mobile ground-based cameras can be used to scale ecological observations, relating pixel information in images to in situ measurements. Currently there are four CENS projects that involve using cameras for scaling ecological observations: 1. Scaling from one individual to the landscape. Pan-Tilt-Zoom cameras can be zoomed in on a tight focus on individual plants and parts of individuals and then zoomed out to get a landscape view, composed of the same and similar species. 2. Estimating photosynthesis over large areas with HDR. High Dynamic Range imaging is a technique to capture an absolute amount of reflected light in an image. For a meadow composed of similarly reflecting species, we can estimate light received by leaves and thus photosynthesis over a wide area. 3. Scaling soil surface temperature measurements. Soil surface temperatures and soil energy balance are related to solar radiation and air temperature. Sunflecks captured with a camera taking panoramic mosaics of images can be used to estimate the radiation load for large areas of unobstructed understory. 4. Expanding plant phenological observations with a nation-wide network of webcams. Twice-daily images from over 1000 internet-connected and freely available cameras have been collected since February 2008. The advance of Spring can be tracked as a "green-up" and related to satellite remote sensing signals.