RT Journal Article SR Electronic T1 Regulation of dopamine release by tonic activity patterns in the striatal brain slice JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.05.22.595411 DO 10.1101/2024.05.22.595411 A1 Boumhaouad, Siham A1 Makowicz, Emily A A1 Choi, Sejoon A1 Bouhaddou, Nezha A1 Balla, Jihane A1 Taghzouti, Khalid A1 Sulzer, David A1 Mosharov, Eugene V. YR 2024 UL http://biorxiv.org/content/early/2024/05/23/2024.05.22.595411.abstract AB Voluntary 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 vivo acute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics than in vivo recordings. 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 those in 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 release ex vivo and in vivo and provides a novel approach to more accurately emulate pre- and post-synaptic mechanisms that control axonal DA release in the acute striatal brain slice.Competing Interest StatementThe authors have declared no competing interest.DADopamineD2RDopamine D2 receptorDHβEDihydro-β-erythroidine hydrobromideFSCVFast-scan cyclic voltammetryGABAGamma-aminobutyric acidGIRKG-protein-coupled inward rectifier potassiumMFBMedium forebrain bundlenAChRNicotinic acetylcholine receptorsRRPReadily releasable poolSNpcSubstantia nigra pars compacta