Our Research
Microglia are dynamic, macrophage-like cells within the CNS. They remove cellular debris and pathogens from surrounding tissue and exert powerful neuroprotective and/or neurotoxic effects during disease and injury. They can also modulate neuronal membrane properties and synapses, positioning these cells as key contributors to physiological and pathological circuit function. Microglia are not equivalent throughout the brain and exhibit specialized phenotypes in different nuclei of the basal ganglia (BG), circuits involved in reward and motivation.
We exploit these regionally specialized phenotypes to study how microglial variation shapes:
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Synaptic function of BG neurons
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Resilience and viability of BG neurons
We also exploit this regional specialization of microglia to:
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Identify cues that regulate basal microglial phenotypes to discover novel strategies for manipulating microglial properties
Causes and consequences of microglial regional specialization within basal ganglia (BG) circuits. An overarching goal of this research program is to promote innovative approaches to treating CNS circuit dysfunction and disease. Microglia are ubiquitous, capable of self-renewal, highly plastic, and can be influenced from the periphery, making them highly attractive targets for therapeutic interventions in a broad range of pathological contexts. By studying the basic biology of BG microglia and their interactions with surrounding neurons as well as their responses to challenges and insults, we hope to provide new insight into pathological alterations that impact BG circuits, such as addiction and other psychiatric illness, neurodegeneration, toxic poisoning, and focal inflammatory conditions.
Imaging. We use high resolution imaging in fixed tissue as well as multiphoton imaging in acute brain slices and in vivo to monitor the dynamic process movements of microglia and their physical interactions with surrounding neurons.
Electrophysiology. We use whole cell patch clamp recordings from both microglia and neurons to interrogate microglial phenotype and measure the impact of microglia on neuronal membrane excitability and synaptic function.
Molecular Biology. We use fluorescence activated cell sorting (FACS) to isolate microglia and neurons from brain tissue for analysis of gene expression, protein content, and organelle function.
Caspase 3+ dying cell being phagocytosed by a nearby microglial cell during early postnatal development.
3D reconstruction of microglial cell morphology in distinct basal ganglia nuclei.
Relative distribution of microglia (Iba1, red) and astrocytes (ALDH1L1-EGFP, white) in the basal ganglia.