fast-scan-cyclic-voltammetry-for-ex-vivo-recording-of-dopamine-release

Fast-Scan Cyclic Voltammetry for <em>Ex Vivo</em> Recording of Dopamine Release

Fast-Scan Cyclic Voltammetry (FCV) is an electrochemical technique that enables real-time detection of oxidisable neurotransmitters, including dopamine ...

University of Exeter Medical School, Hatherly Laboratories

Regional changes in corticostriatal transmission induced by phasic dopaminergic signals are an essential feature of the neural network responsible for instrumental reinforcement during discovery of an action. However, the timing of signals that are thought to contribute to the induction of corticostriatal plasticity is difficult to reconcile within the framework of behavioural reinforcement learning, because the reinforcer is normally delayed relative to the selection and execution of causally-related actions.

Sensory Reinforced Corticostriatal Plasticity.

Cholinergic interneurons (ChIs) are important for learning and memory. They exhibit a multiphasic excitation-pause-rebound response to reward or sensory cues indicating a reward, believed to gate dopamine-dependent learning. Although ChIs receive extensive top-down inputs from the cortex and bottom-up inputs from the thalamus and midbrain, it is unclear which inputs are involved in the development of ChI multiphasic activity.

The Integration of Top-down and Bottom-up Inputs to the Striatal Cholinergic Interneurons.

Depolarization of axons is necessary for somatic action potentials to trigger axonal neurotransmitter release. Here we show that striatal cholinergic interneurons (ChIs) and nicotinic receptors (nAChRs) on mouse dopamine axons interrupt this relationship. After nAChR-mediated depolarization, dopamine release by subsequent depolarization events was suppressed for ~100 ms. This suppression was not due to depletion of dopamine or acetylcholine, but to a limited reactivation of dopamine axons after nAChR-mediated depolarization, and is more prominent in dorsal than in ventral striatum. In vivo, nAChRs predominantly depressed dopamine release, as nAChR antagonism in dorsal striatum elevated dopamine detected with optic-fiber photometry of dopamine sensor GRAB and promoted conditioned place preference. Our findings reveal that ChIs acting via nAChRs transiently limit the reactivation of dopamine axons for subsequent action potentials in dopamine neurons and therefore generate a dynamic inverse scaling of dopamine release according to ChI activity.

Article	Year
Sensory Reinforced Corticostriatal Plasticity. Current neuropharmacology\| PubMed ID: 37533245	2024
The Integration of Top-down and Bottom-up Inputs to the Striatal Cholinergic Interneurons. Current neuropharmacology\| PubMed ID: 38420787	2024
An axonal brake on striatal dopamine output by cholinergic interneurons. Nature neuroscience\| PubMed ID: 40082616	2025

Yan-Feng Zhang

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