XU LABORATORY
INSTITUTE FOR CELL ENGINEERING
DEPARTMENT OF NEUROLOGY | JOHNS HOPKINS SCHOOL OF MEDICINE
Conceptual representation of inflammation on neural diseases
Anatomical illustration of the blood-brain barrier interface
Dissecting circuits of the basal ganglia
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The basal ganglia are a series of interconnected nuclei that are involved in motor function, emotional processing, action selection, and cognitive function. These diverse functions are heavily influenced by midbrain dopamine neurons.
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Loss of dopamine neurotransmission in the basal ganglia underlies many aspects of Parkinson's disease (PD). While much emphasis is placed on the role of dopamine in motor function, little is known about how loss of dopamine contributes to non-motor aspects of PD.
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In our lab, we believe that defining the neural circuitry of midbrain dopamine neurons is an essential step towards better understanding and treatment of non-motor symptoms of PD.
A. Behensky
Tools to define circuits
We use the 'TVA-tag' approach to identify neurons that make monosynaptic connections to dopamine neurons. This method uses a modified recombinant Rabies virus encoding a fluorescent protein, allowing us to anatomically identify inputs to dopamine neurons.
I. Wu
Our Rabies virus encodes a fusion between EGFP and a ribosomal protein. This is useful because it allows us to visualize where dopamine neuron input neurons reside and we can also purify translating mRNAs from dopamine neuron innervating cells using a method call TRAP (translating ribosome affinity purification).
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We can sequence the purified mRNA from these cells, genetically defining these innervating cell types. Using this information we can design strategies to study their function in dopamine neuron circuits.
Many types of dopamine neurons
A. Behensky
Midbrain dopamine neurons are not a uniform population of cells. Using novel and existing transgenic recombinase lines, we are isolating genetically defined populations of dopamine neurons to study their inputs, outputs, and molecular and functional properties.
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The image above illustrates how dopamine neurons can be separated into genetic classes using recombinase lines. In this cashew are separating dopamine neurons primarily populating the substantia nigra pars compact (SNc,green) from neurons that make up the ventral tegmental area (VTA, red). Since the SNc neurons are the most vulnerable population PD, these cells are the focus of our current studies.