Enhancing synaptic and structural plasticity by manipulating PirB

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DESCRIPTION (provided by applicant): When the brain is developing, it uses specific rules to determine if two neurons should form a synapse between them or not. For example, neurons that "fire together" will often "wire together", and those that are "out of synch, lose their link" These synaptic plasticity rules are very important in determining what portion of the cortex and which cells will be devoted to certain processes, such as binocular vision. The Shatz laboratory has found that PirB (paired immunoglobulin-like receptor B), an immune receptor found normally in neurons and having a human ortholog, acts as a "brake" on plasticity in the mouse visual cortex. Removing PirB genetically in the mouse (i.e. "removing the brake") enhances plasticity in visual cortex. "Removing the brake" on cortical plasticity in the adult could be important in recovering from injury (e.g. stroke), neurodegenerative disease (e.g. Alzheimer's), or developmental disorders (e.g. autism or amblyopia). Therefore, one of the greatest priorities of the lab is to understand the cellular and molecular mechanisms that underlie the enhanced plasticity that comes from removing PirB genetically from the mouse, or when PirB is directly blocked. The first goal of this project is to understand if PirB has an effect on synaptic plasticiy rules (such as the rule "fire together, wire together") that cause plasticity to decrease in adulthood. This will be done by comparing normal brains and brains lacking PirB using cortical slice electrophysiology. The second goal of this project is to directly block the function of PirB and see if these and other plasticity rules can be changed immediately. This will be observed using cortical slice electrophysiology and live two-photon excitation microscopy. If cells do modify their structure and synaptic plasticity rules, then acutely "removing the brake" by blocking PirB could provide new ways to overcome injury, disease, or developmental disorders of the brain.