Dorothy P Schafer PhD
|Institution||University of Massachusetts Medical School|
|Address||University of Massachusetts Medical School|
55 Lake Ave North
Worcester MA 01605
|Institution||UMMS - Graduate School of Biomedical Sciences|
|Department||Immunology and Microbiology Program|
|Institution||UMMS - Graduate School of Biomedical Sciences|
Dori Schafer earned her Bachelor’s degree in Neuroscience and Behaviour from Mount Holyoke College in 2001. She attended graduate school at the University of Connecticut Health Center in Matthew Rasband’s lab where she used rodent models to study neuron-glia interactions regulating assembly and maintenance of functional, polarized domains along the axon, nodes of Ranvier and axon initial segments. Upon completion of her PhD in 2008, she began her postdoctoral training in the laboratory of Beth Stevens at Boston Children’s Hospital. While in the Stevens lab (2008-2014), she studied the role of microglia, the resident CNS myeloid-derived cell, in mammalian synapse development and plasticity. She was recently hired in 2014 as a tenure-track Assistant Professor in the Department of Neurobiology at The University of Massachusetts Medical School. Her laboratory utilizes a combination of molecular biology and high resolution imaging to understand how neurons and glia communicate with one another to regulating synapse development and plasticity.
Neuron-Glia Interactions Regulating Synaptic Circuit Development and Plasticity
The primary focus of our research is to understand the role of glial cells in synapse development and plasticity in the healthy and diseased nervous system. To achieve and maintain the precise synaptic connectivity characteristic of the mature organism, synapses must be plastic. This is particularly true in the developing nervous system where, during critical periods of heightened plasticity, spontaneous activity and experience drive synapse remodeling. The importance of these processes are further emphasized in neurodevelopmental and neuropsychiatric disorders, where it is becoming clear that critical period plasticity is particularly vulnerable to disruption.
It is also emerging that glia are far more than “brain glue,” playing active roles in shaping and maintaining the nervous system. Recently, we demonstrated a surprising role for microglia, the resident CNS immune cells and professional phagocytes, in the elimination of excess synapses that form in the developing mammalian visual system. Specifically, we showed that microglia phagocytose synapses in the developing brain in an activity-dependent manner. Genetic or Pharmacological disruption of microglial phagocytic signaling resulted in sustained deficits in brain wiring. However, several fundamental questions remain. How do microglia, as well as other glial cell types, respond on a cellular and molecular level to changes in synaptic activity? How do these responses ultimately translate to development and/or function of synaptic circuits? How do glia contribute to abnormal synaptic circuit development associated with neurodevelopmental and neuropsychiatric diseases (e.g., autism, schizophrenia, etc.)? To address these questions, the lab has developed novel strategies to image glia-synaptic circuit interactions by 2-photon in vivo live imaging in awake, behaving mice. In addition, we have developed techniques to dissect glia-specific molecular mechanisms underlying synaptic plasticity.
Investigating Glial Responses to Changes in Sensory Experience in Real Time
Sensory experience is known to drive synapse remodeling throughout the CNS, particularly during critical periods in development. The developing mammalian visual system is a classic example. We have developed strategies to simultaneously visualize glial cells and specific synaptic circuits known to undergo experience-dependent remodeling in the mouse visual cortex of awake, behaving mice. In addition, we aim to extend these studies to image responses of other glial cell populations, including myelinating oligodendrocytes and astrocytes, to changes in sensory experience.
Dissecting the molecular mechanisms underlying glial responses to sensory experience
Glia are known to respond to changes in neural activity, but molecular mechanisms underlying these responses are just beginning to be deciphered. Projects in the lab are designed to identify glia-specific molecules that change in response to changes in neural activity and understand how these genes regulate glial cell biology. To begin, we have now identified several microglia-specific genes that change following manipulation of visual sensory experience.
Understanding the functional consequences of glia-synapse interactions in health and disease
The functional significance of glial responses to changes in activity and interactions with synapses are still relatively unknown. Beginning with microglia, we are using cell-specific genetic approaches to understand how these cell types contribute to the structure and overall function of synaptic circuits. Furthermore, it is now appreciated that abnormalities in synaptic connectivity and glial cells are hallmarks of several neurodevelopmental and neuropsychiatric disorders. Thus, ongoing projects in the lab are also aimed at understanding how CNS glial cells contribute to this abnormal brain circuitry.
There are a variety of rotation projects that use a variety of imaging and biochemical techniques to assess glial function in the CNS. The main projects are highlighted below.
1. Assessing glial responses to changes in neural activity by in vitro and in vivo live imaging.
2. Identifying molecular mechanisms underlying activity-dependent changes in glial cells.
3. Assessing structural and functional changes in brain wiring in response to manipulation of glial cell function.
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