Dopamine axons: immense networks for dynamically gating dopamine transmission

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Midbrain dopamine neurons that innervate the mammalian striatum play critical roles in motivation, movement and reinforcement learning. Furthermore, dopamine transmission is dysregulated, or targeted by therapy, in several psychomotor disorders including Parkinson’s disease, addictions, Huntington’s disease, and ADHD amongst others. The striatal axon arbours formed by midbrain dopamine neurons are among the most extensive, branched axons seen within the central nervous system, containing hundreds of thousands of varicosities per neuron. We are identifying the diverse range of mechanisms that operate on these extraordinary arbours to govern how activity is relayed into dopamine transmission, as well as how these might impact on vulnerability or therapy in disease. We find that dopamine transmission is gated dynamically by intrinsic ionic mechanisms on dopamine axons that govern axonal excitability and short-term plasticity, which surprisingly include the dopamine uptake transporter, as well as by networks of other striatal cells, both neuronal (ACh interneurons and networks, GABA tone) and non-neuronal (astrocytes), and by proteins associated with Parkinson’s. I will highlight some of our recent findings in mouse striatum to show how dopamine transmission does not have a fixed relationship to somatic activity but is gated powerfully at the level of dopamine axons.