Dendrite-specific synaptic inputs onto dopaminergic SNc neurons

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Abstract

Substantia nigra pars compacta (SNc) dopaminergic neurons integrate synaptic inputs through dendrites that project laterally within the SNc and ventrally into the substantia nigra pars reticulata (SNr), which then determines dopaminergic output. We use spatially-specific optogenetics to map excitatory subthalamic nucleus (STN) and pedunculopontine nucleus (PPN) as well as inhibitory SNr inputs that provide feedforward inhibition onto SNc neurons. Using multiple GABAergic mouse lines, we find that SNr inputs selectively inhibit SNc somas and proximal dendrites without preference for SNr versus SNc dendrites. Using glutamatergic mouse lines, we find that PPN inputs selectively excite somas and proximal dendrites, while STN inputs selectively excite SNr dendrites, mirroring dendrite-selective inhibition from striosomes. These findings reveal a high level of spatial organization in SNc synaptic inputs and point to separate functional roles for STN versus PPN control of dopaminergic activity.

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