Axonal mechanisms underlying presynaptic short-term plasticity of dopamine release in striatum

Thesis

Dopamine (DA) signalling plays a central role in the functions of the basal ganglia, supporting behavioural processes such as action selection and reinforcement learning. Consequently, dysfunction of DA release is implicated in a wide range of neurological and psychiatric disorders, including Parkinson’s disease and addiction.

DA is released from an extensively-branched axonal arbor in the striatum, but it remains unclear how the characteristics of these complex axons influence the short-term plasticity of DA release. This thesis uses fast-scan cyclic voltammetry and patch-clamp electrophysiology in slices of mouse striatum to study the axonal factors that shape the conversion of firing activity in midbrain DA neurons to DA release in the striatum.

Firstly, short-term plasticity of DA release was shown to be governed by a region-specific hierarchy of mechanisms related to Ca²⁺ dynamics at DA release sites, and to excitability of DA axons in striatum, which was maintained by the dopamine transporter (DAT). Second, tonic background activity in DA neurons was shown to enhance the contrast of DA signals evoked by bursts, in a region-specific manner, and was also regulated by the DAT. Third, release of γ-amino butyric acid (GABA) from DA axons was shown to be insensitive to regulation by the DAT, in contrast to the release of DA.

These data suggest that the characteristics of DA axons, particularly expression of the DAT, can powerfully regulate short-term plasticity of DA release in a region-specific manner. These findings extend our understanding of the regulation of DA signalling and may have implications for the manner in which presynaptic activity in DA neurons is read out as DA release across striatal regions.

Authors: Condon, M

• DOI: 10.5287/ora-kknyobj2m
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford