Caley Burrus (Cagla Eroglu Lab)
“What is the role of Huntingtin in CNS development and function?” (scroll down for abstract)
Na Young Jun (Greg Field Lab)
“Optimal spatial arrangement of ON and OFF encoders in the noisy world - under the perspective of information efficiency”
Burrus abstract: Huntington’s Disease (HD) is a fatal, inherited disease caused by an autosomal dominant polyglutamine expansion mutation near the N-terminus of the Huntingtin (Htt) protein. Patients with HD suffer from progressive motor, cognitive, and psychiatric impairments, along with significant degeneration of the striatal projection neurons (SPNs) of the striatum. The dominant nature of the Htt mutation has led to the widely-accepted hypothesis that HD is caused by a toxic gain-of-function of mutant Htt protein. Recent findings suggest that loss of Htt function due to dominant-negative effects of the mutant protein also play important roles in HD. However, the role of Htt in the health and function of the SPNs is not yet known, leaving critical aspects of HD pathology unexplored. To investigate this question, here we conditionally deleted Htt from specific subpopulations of striatal projection neurons (SPNs) using the Cre-Lox system. We determined that loss of Htt in SPNs leads to aberrant synaptic connectivity and function within the basal ganglia, along with dysregulated motor function. We also discovered that SPNs require Htt for longevity, as SPNs lacking Htt (Htt cKO) degenerate in an aging-dependent manner. While Htt cKO SPNs do not appear to die via apoptosis, there is significant reactive gliosis present in the striatum at the time when SPNS are degenerating, reminiscent of HD. Collectively, these results demonstrate that SPNs require Htt for their health, function, and survival with aging.
Jun abstract: Early sensory systems encode incoming signals via two parallel pathways: ON and OFF. ON pathways encode increments of the intensity of the signals, and OFF pathways encode the decrements. This parallel processing is ubiquitous in all kinds of sensory systems, and it distinguishes animals’ sensory systems from machine light or chemical detectors. In this context, how to spatially arrange ON and OFF receptive fields in the presence of various noise sources is a fundamental question in the field of neuroscience. In this paper, we tackle the question in the early visual system. Using a previously proposed model for efficient coding of natural scenes by RGCs, we calculate the optimal spatial arrangements of receptive fields and find that mosaic alignment depends on both the levels of input noise (to the retina) and output noise (from RGCs). In addition, using a simplified mathematical model, we demonstrate the existence of a second-order phase transition between the two mosaic alignments, as a function of the distribution of stimuli and noise parameters. These results provide a theoretical explanation for the highly conserved organizations of parallel ON and OFF pathways in the retina and their arrangements with respect to one another.