Claire E Le Pichon

Learn More
The mammalian odorant receptors (ORs) comprise a large family of G protein-coupled receptors that are critical determinants of both the odorant response profile and the axonal identity of the olfactory sensory neurons in which they are expressed. Although the pathway by which ORs activate odor transduction is well established, the mechanism by which they(More)
A remarkable feature of peripheral olfactory projections in mammals is the convergence of axons from olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) into the same glomeruli. There is mounting evidence that the ORs play critical roles in glomerular formation. However, it remains unclear how the OR exerts its function of sorting(More)
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD). Although biochemical studies have shown that certain PD mutations confer elevated kinase activity in vitro on LRRK2, there are no methods available to directly monitor LRRK2 kinase activity in vivo. We demonstrate that LRRK2(More)
The word somatosensation comes from joining the Greek word for body (soma) with a word for perception (sensation). Somatosensory neurons comprise the largest sensory system in mammals and have nerve endings coursing throughout the skin, viscera, muscle, and bone. Their cell bodies reside in a chain of ganglia adjacent to the dorsal spinal cord (the dorsal(More)
The normal physiological function of the prion protein PrP(C) remains elusive despite its widespread expression, particularly throughout the nervous system. A critical step toward identifying its function is to precisely localize its pattern of expression. Historically, the immunolocalization of PrP(C) has proved to be notoriously difficult and(More)
Neurogenesis persists in the olfactory system throughout life. The mechanisms of how new neurons are generated, how they integrate into circuits, and their role in coding remain mysteries. Here we report a technique that will greatly facilitate research into these questions. We found that electroporation can be used to robustly and selectively label(More)
The prion protein PrPC is infamous for its role in disease, but its normal physiological function remains unknown. Here we found a previously unknown behavioral phenotype of Prnp−/− mice in an odor-guided task. This phenotype was manifest in three Prnp knockout lines on different genetic backgrounds, which provides strong evidence that the phenotype is(More)
Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding mode and specific design parameters to(More)
BACKGROUND The senses of touch and proprioception evoke a range of perceptions and rely on the ability to detect and transduce mechanical force. The molecular and neural mechanisms underlying these sensory functions remain poorly defined. The stretch-gated ion channel PIEZO2 has been shown to be essential for aspects of mechanosensation in model organisms.(More)
There is a high demand for potent, selective, and brain-penetrant small molecule inhibitors of leucine-rich repeat kinase 2 (LRRK2) to test whether inhibition of LRRK2 kinase activity is a potentially viable treatment option for Parkinson's disease patients. Herein we disclose the use of property and structure-based drug design for the optimization of(More)