The SINTN seminar series proudly presents

Lisa Boulanger

Regulation of synaptic transmission and synaptic plasticity by MHCI

Lisa Boulanger Ph.D.
Assistant Professor
Department of Molecular Biology and Princeton Neuroscience Institute

Website: Boulanger lab Web Site

Abstract:

My laboratory is interested in how specific immune proteins, members of the major histocompatibility complex, class I (MHCI) contribute to the formation, function, modification, and disruption of neuronal connectivity. MHCI proteins are best known for their role in the immune system, but are also dynamically expressed in the healthy mammalian central nervous system, suggesting they may have non-immunological functions. Indeed, studies I performed as a postdoc in the Shatz lab demonstrated that MHCI is critical for normal activity-dependent plasticity in the developing and adult brain: in mice genetically deficient for MHCI, activity-dependent remodeling of developing visual projections is impaired, and frequency-dependent hippocampal synaptic plasticity is shifted in favor of potentiation (Huh et al., 2000). Subsequent studies in my lab have been aimed at understanding how MHCI immune proteins regulate the structural and functional plasticity of synapses. We have found that MHCI is not required for all forms of plasticity, but rather selectively regulates plasticity driven by activation of the NMDA-type glutamate receptor (NMDAR). New evidence from our lab suggests that the specificity of this deficit likely reflects a novel role for MHCI as an endogenous regulator of NMDAR function. In the adult hippocampus, NMDAR-dependent plasticity is thought to underlie certain forms of learning and memory, and indeed we find that the changes in NMDAR-dependent plasticity in MHCI-deficient animals are associated with selective disruption of NMDAR-dependent learning and memory. These results raise the provocative possibility that MHCI could link changes in immune signaling to cognitive impairment following illness or injury. Ongoing studies in the lab include determining the molecular mechanisms by which MHCI limits NMDAR function, identifying novel binding partners for MHCI in neurons, and examining how dysregulation of MHCI expression may contribute to the pathogenesis and progression of neurological disorders including autism and schizophrenia. We are also interested in what the distinct roles of MHCI in the brain and in the immune system can tell us about the mysterious evolutionary origins of adaptive immunity.

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