Regulation of dopamine release by tonic activity patterns in the striatal brain slice

Abstract

AbstractVoluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons that extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: a low-frequency tonic activity that is intrinsically generated, and superimposed high-frequency phasic bursts that are driven by synaptic inputs.Ex vivoacute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics thanin vivorecordings. To investigate the relationship between phasic and tonic neuronal activity, we stimulated the slice in patterns intended to mimic tonic activity, which were interrupted by a series of burst stimuli. Conditioning the striatal slice with low-frequency activity altered DA release triggered by high-frequency bursts, and produced kinetic parameters that resemble thosein vivo. In the absence of applied tonic activity, nicotinic acetylcholine receptor and D2 dopamine receptor antagonists had no significant effect on neurotransmitter release driven by repeated burst activity in the striatal brain slice. In contrast, in tonically stimulated slices, D2 receptor blockade decreased the amount of DA released during a single burst and facilitated DA release in subsequent bursts. This experimental system provides a means to reconcile the difference in the kinetics of DA releaseex vivoandin vivoand provides a novel approach to more accurately emulate pre- and post-synaptic mechanisms that control axonal DA release in the acute striatal brain slice.