Date(s) - 08/15/2014
8:00 pm - 9:00 pm
Friday Evening Lecture Series – “Surprise at the Synapse: Developmental Critical Periods and Disease – Can Knowledge of One Help Cure the Other?”
Carla Shatz, Stanford University
August 15, 2014, 8:00 PM, Lillie Auditorium
Connections in adult brain are highly precise, but they do not start out that way. Precision emerges during developmental critical periods as synaptic connections prune and remodel in a process requiring using your brain (neural activity). Activity also regulates neuronal gene expression. Major Histocompatibility Class I (MHCI) genes –famous for their role in immunity- were unexpectedly discovered to be regulated by vision, and also expressed in neurons, and located at synapses. To assess requirements for MHCI in CNS, mutant mice lacking specific MHCI genes were studied. Synapse pruning in developing visual system fails, and synapse plasticity in visual cortex is greater than normal. In a search for receptors that could interact with neuronal MHCI, the immune receptor PirB was found in mouse brain. In mice lacking PirB, visual system plasticity is also increased and synapse pruning in cortex fails. The commonality of phenotypes present in both types of mutant mice suggests a model in which PirB receptor interacts with MHCI ligands in neurons. Moreover, without PirB, mice do not succumb to the devastating effects of Beta Amyloid- known to be responsible for synapse and memory loss in Alzheimer’s Disease. Together, results imply that these molecules, thought previously to function only in immunity, also act at neuronal synapses to limit how much- or how quickly- synapse strength changes in response to new experience. Changes in their function could contribute to developmental disorders such as Schizophrenia, and even to the synapse loss in Alzheimer’s Disease.