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Circuitry and Brain-Body Interactions

The circuitry and brain-body interactions theme focuses on basic research aimed at understanding how the circuits that underlie priority brain regions are affected in PD and how they may contribute to disease initiation and progression. This theme focuses on investigating how communication between the brain and areas outside the brain are affected over the disease course.

Highlights

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Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2G2019S model of Parkinson’s disease

Several studies have revealed that midbrain dopamine (DA) neurons, even within a single neuroanatomical area, display heterogeneous properties. Team Awatramani developed an optimized pipeline for single-nuclear RNA sequencing (snRNA-seq) and generated a high-resolution hierarchically organized map revealing 20 molecularly distinct DA neuron subtypes belonging to three main families.

Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease

Age is a critical PD risk factor, but its role in dopamine neuron degeneration remains unclear. Team Cragg linked aging to increased vulnerability by showing that 13 candidate PD GWAS genes are enriched in dopamine neurons and oligodendrocytes in aged brains, highlighting that these cell types may be more susceptible to aging processes than other neuronal types.

A topographical atlas of α-synuclein dosage and cell type-specific expression in adult mouse brain and peripheral organs

Team Schlossmacher has developed an integrated atlas provides insight into the cellular topography of αSyn, and provides a quantitative map to test hypotheses about the role of αSyn in network vulnerability, and thus serves investigations into PD pathogenesis and other α-synucleinopathies.

Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering

L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinson’s disease. Team Surmeier, using high-resolution motion sensors and calcium imaging in rodent PD models, showed that distinct dopamine neuron subsets encode LID behaviors.

Our Teams

These teams focus on high-priority research aimed at understanding how the circuits that underlie priority brain regions are affected in PD and how they may contribute to disease initiation and progression. These teams also investigate how communication between the brain and areas outside the brain are affected over the disease course.