Overview

It is critical to learn what sensory inputs are predicting and react fast to receive a reward and avoid punishment. I am interested in understanding the cellular mechanisms underlying this learning process.   

Dopamine and acetylcholine signals in striatum are believed to play critical roles in reward-related learning, and dysfunction of these two systems can lead to severe diseases, such as Parkinson’s disease. My lab is to explore these two neurotransmitter systems, which remain poorly understood.

My PhD work 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). Furthermore, I investigated how the superior colliculus may regulate rapid phasic dopamine responses in visual classical conditioning (Zhang et al., under revision). Moreover, I explored how striatal cholinergic interneurons integrate top-down and bottom-up inputs in vivo (Zhang† and Reynolds, Current Neuropharmacology, 2024).

After joining Prof Stephanie Cragg's lab at Oxford University as a Postdoctoral Researcher, 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 single-unit recording, whole cell patch clamp 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). I revealed a novel mechanism by which cholinergic interneurons regulate the excitability of striatal dopamine axons, thereby influencing dopamine release in the striatum (Zhang et al., in revision). Additionally, I discovered the significant impact of tonic dopamine activity on phasic dopamine release in both health and disease states. My study also led to 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). 

Qualifications

• PhD
• PGDipSci (distinction)
• BSc

Links

• ORCID
• Google Scholar
• Twitter

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Research

Research interests

My laboratory focuses on understanding cellular mechanisms underlying learning and memory, including how information flows in neural circuits during reinforcement learning, the pre-synaptic modulation of neurotransmitter release, and how learning and memory may form at synapses. I am also interested in exploring potential new treatment avenues for neurodegenerative and other neurological disorders, such as Parkinson's disease and addiction.

Techniques we use:

• Patch clamp
• Ex vivo and in vivo fast-scan cyclic voltammetry (FCV) recordings
• Calcium imaging
• Next-generation neurotransmitter imaging
• In vivo single-unit recordings
• Behavioural tasks
• Optogenetic and chemogenetic manipulations
• Computational modelling.

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Publications

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External Engagement and Impact

Editorial responsibilities

Review editor at Frontiers in Molecular Neuroscience

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Teaching

Modules

2023/24

• NEUM003 - Behavioural and Systems Neuroscience

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