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Gaucher disease (GD), a common lysosomal storage disorder (LSD), is caused by
mutations in the GBA1 gene. This gene encodes the lysosomal hydrolase
glucocerebrosidase (GlcCerase), and in the disease, the lipid glucosylceramide
(GlcCer) accumulates within the cell. Although neuronopathic Gaucher disease (nGD) was described over a hundred years ago, little is known about the mechanisms leading from GlcCer accumulation to neuronal cell death and inflammation. Recently, our laboratory identified induction of the type 1 interferon (IFN) response in nGD mice. The IFN response is the fundamental cellular defense mechanism against viral infection, however it can also be induced in the absence of infection. Ablation of the IFN receptor (IFNAR) did not have any effect on the viability of nGD mice. Therefore, we took availability of quadrat deficient mice where four adaptors of main pathogen recognition receptors (PRR) are blocked. Ablation of all the pathways leading to IFN production did not have effect on mice life span. Nevertheless, we utilized these results to conduct an RNA sequencing study with the goal of defining what are the inflammatory pathways lead to disease development and, eventually, to mice death.

In many tasks, such as mazes or social interactions, effective decision making typically requires enumerating the expected outcomes of candidate actions over a series of subsequent events. Because of the computational complexity of such evaluation, it is believed that human and animal brains use a range of shortcuts to simplify or approximate it. I review behavioral and neural evidence that humans rationally trade off exact and approximate evaluation in such sequential decision making. This research offers a new perspective on healthy behaviors, like habits, and pathological ones, like compulsion, which are both viewed as approximate evaluations that fail to incorporate experiences relevant to a decision and instead rely on inappropriate or out-of-date evaluations. I also present new theoretical and experimental work that aims to address the positive counterpart to such neglect: which particular events are considered, in which circumstances, to support choice. This brings the reach of the framework to many new phenomena, including pre-computation for future choices, nonlocal activity in the hippocampal place system, consolidation during sleep, and a new range of disordered symptoms such as craving, hallucinations, and rumination.

TBA