Contact information
Websites
- Oxford Parkinson's Disease Centre
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New insights into the role of dopamine in reinforcement learning
A new study from Dr Yanfeng Zhang has uncovered the first evidence that dopamine-dependent long-term potentiation is also gated by the pause of striatal cholinergic interneurons and the depolarisation of the striatal spiny projection neurons. This discovery overturns previous ideas that the phasic dopamine release is the only factor gate corticostriatal synaptic plasticity, thus changing our understanding of dopamine functions in reinforcement learning.
Research groups
Yanfeng Zhang
PhD
Visiting lecturer
It is critical to learn what sensory inputs are predicting, and react fast to receive a reward and avoid a punishment. My research focuses on the cellular mechanisms underlying this learning process, more specifically, the roles of dopamine and acetylcholine systems in reinforcement learning.
During my PhD study with Prof John Reynolds, I revealed that the pauses in cholinergic interneurons may define the time window for phasic dopamine to induce plasticity, and depolarisation of SPNs constrains the plasticity to the target synapses (Reynolds, ..., Zhang†, Nature Communications, 2022). I also investigated how superior colliculus may gate visual classical conditioning (Zhang et al., in revision), and how striatal cholinergic interneurons integrate top-down and bottom-up inputs in vivo.
After joining Cragg lab, I characterised how cortical and thalamic inputs summate in cholinergic interneurons ex vivo with optogenetic manipulations (Kosillo, Zhang et al., 2016, Cerebral Cortex). By combining in vivo observation during my PhD, patch clamping recordings in Cragg lab and a computational model, I revealed the multiphasic activity in cholinergic interneurons is driven by excitatory input through a rectifying potassium current and modulated by dopamine signal (Zhang et al., Neuron 2018). Furthermore, I recently revealed a new mechanism of how cholinergic interneurons regulate the excitability of striatal dopamine axon and, therefore, gate dopamine release in the striatum (Zhang et al., in revision). I am working on a project to investigate how tonic dopamine activity gates phasic dopamine release in health and disease. I am also interested in potential treatments for Parkinson’s disease (patent application filed).
I also collaborated with E.N.T. surgeons to map sensory input from different parts of the vestibular and auditory systems stratified across the hippocampus's different subregions (Hitier*, Zhang* et al., 2020, Hearing Research; Hitier*, Zhang* et al., 2021, Hearing Research, cover story).
Key publications
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Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation.
Journal article
Zhang Y-F. et al, (2018), Neuron, 98, 918 - 925.e3
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Coincidence of cholinergic pauses, dopaminergic activation and depolarization drives synaptic plasticity in the striatum.
Working paper
Zhang Y-F. et al, (2019)
Recent publications
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An axonal brake on striatal dopamine output by cholinergic interneurons.
Journal article
Zhang Y-F. et al, (2025), Nat Neurosci
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Coincidence of cholinergic pauses, dopaminergic activation and depolarisation of spiny projection neurons drives synaptic plasticity in the striatum
Journal article
Reynolds JNJ. et al, (2022), Nature Communications, 13
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Revisiting dopamine-acetylcholine imbalance in Parkinson's disease: Glutamate co-transmission as an exciting partner in crime.
Journal article
Zhang Y-F. and Cragg SJ., (2021), Neuron, 109, 1070 - 1071
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Stratification of hippocampal electrophysiological activation evoked by selective electrical stimulation of different angular and linear acceleration sensors in the rat peripheral vestibular system.
Journal article
Hitier M. et al, (2021), Hear Res, 403
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The effects of selective electrical stimulation of the rat cochlea on hippocampal field potentials.
Journal article
Hitier M. et al, (2020), Hear Res, 395

