Dopaminergic modulation of substantia nigra pars reticulata neurons in prodromal and parkinsonian states

Project: Research project

Project Details

Description

Our working hypothesis that dendritic DA suppresses both phasic and tonic GABA release from pallidonigral synaptic terminals, resulting in an attenuation of the impact of the indirect pathway on basal pacemaking activity in SNr neurons – mirroring the effects of DA on the indirect pathway in the striatum and GPe proper. With the loss of SNr DA release, the full consequences of basal ganglia pathophysiology originating in the striatum and GPe are brought to bear on SNr neurons, resulting in the broadcast of this pathophysiology to motor and sleep circuits – disrupting their function and resulting in cardinal symptoms of PD. To test this hypothesis, I propose to purse three specific aims. AIM 1: How does DA modulate pallidonigral synaptic transmission in healthy mice? AIM 2: What are the consequences of striatal and later nigral DA depletion on pallidonigral synaptic transmission in the MC1-Park mouse? AIM 3: Are SNr neurons participating movement and sleep circuits modulated by DA similarly and are the consequences of DA depletion the same in these two populations?
StatusActive
Effective start/end date8/1/217/31/24

Funding

  • William N. & Bernice E. Bumpus Foundation (Surmeier AGMT 7/20/21)

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