Liu C 2021 Spatial and Temporal Scales of Dopamine Transmission.pdf

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• triggers synchronized release from a population of neurons, which leads to overlap of the dopamine sig ­ nalling domains

• additional important consideration is the rela ­ tionship between diffusion and dopamine reuptake via the dopamine transporter (DAT).

• By contrast, burst firing is an activity pattern of a single dopamine neuron and does not strongly enhance dopamine release from that neuron, owing to prominent use -​ dependent depression

• Striatal dopamine levels are highly dynamic and fluctu ­ ate on different timescales, with sub -​ second transients, ramps that may last for several seconds and oscillations on the timescale of hours

• uncertain from where on the extensively branched stri ­ atal axons dopamine is released and how the secretory mechanisms involved can account for these dynamic signals

• Because most dopamine transmission is not naturally associated with postsynaptic currents, many studies rely on electrochemical measurements that sample dopamine from a large area and lack either temporal resolution or dopamine selectivity

• started to change with the development of fluorescent

• reporters and dopamine -​ sensitive ion channels

• Accumulating evidence now indicates that dopamine signalling is not only temporally dynamic but also spatially organized

• Dopamine varicosities

• dopamine terminals are called varicosities , and many of them do not form classical synapses and are not associated with defined postsynap ­ tic structures

• vesicular dopamine loading is essential for dopamine release 45 – 47 and that quantal release events can be detected 48 – 51 established that most dopamine is released through vesicle fusion

• functional heteroge ­ neity across varicosities, with only 20% of them secreting above the detection threshold

• possible that not all varicosities are release competent, or that there is strong heterogeneity in the release properties between varicosities

• Dopamine neurons co -​ release glutamate and GABA

• In striatal dopamine axons, glutamate release is segregated from dopa ­ mine rel ease

• Symmetric synapses , such as those detected in the dopamine system 43 , 57 , 58 , are typically GABAergic, and the optogenetic activation of dopa ­ mine axons indeed robustly triggers the release of dopamine and GABA from the same vesicular compart ­ ment

• identification of sites for GABA transmission of dopamine neurons may reveal the source of dopamine release

• ogical analyses suggest that most GABAergic markers are not detected in the subset of varicosities that form synaptic contacts with target cells

• hether these synaptic varicosities of dopamine axons are the source of GABA and dopamine