Background pattern of a brain with neural connections

Team Dombeck

Redefining PD pathophysiology mechanisms in the context of heterogeneous substantia nigra neuron subtypes

The widely held view is that degeneration of substantia nigra pars compacta (SNc) dopamine (DA) neurons causes striatal DA deficits that underlie the motor symptoms of Parkinson’s disease (PD). However, our studies have uncovered putative pro-locomotor and anti-locomotor DA neuron subtypes in the SNc, and the pro-locomotor subtype exhibits selective vulnerability in PD. Thus, we hypothesize that Parkinsonian motor dysfunction results from an imbalance in pro-and anti-locomotor DAergic signaling. Our multidisciplinary team of researchers will investigate this under-appreciated heterogeneity of SNc DA neurons, and its relevance for PD, in terms of cell-autonomous and circuit-level dysfunction.

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Circuit dysfunctionDopamine neuron subtypesMotor symptoms

Leadership

Dan Dombeck

Dan Dombeck

Lead PI (Core Leadership)

Rajeshwar Awatramani

Rajeshwar Awatramani

Co-PI (Core Leadership)

Mark Bevan

Mark Bevan

Co-PI (Core Leadership)

Tom Hnasko

Tom Hnasko

Co-PI (Core Leadership)

Loukia Parisiadou

Loukia Parisiadou

Co-PI (Core Leadership)

Ellen Fruzyna

Ellen Fruzyna

Project Manager

Project Highlights

Para-subthalamic nucleus adjoins subthalamic nucleus and medial forebrain bundle, major DBS-targets in Parkinsons disease, OCD, and depression

The subthalamic nucleus (STN) is a deep brain stimulation (DBS) treatment target for several disorders of vastly different symptoms, including Parkinsons disease (PD) and obsessive compulsive disorder (OCD). The STN is located in close proximity to the superolateral branch of the medial forebrain bundle (slMFB), a recent DBS target for...

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