Research

From molecular anatomy to circuit-level behaviour.

Four interlocking themes drive our work. Each combines genetic dissection of cell types with circuit-level perturbation and quantitative behaviour.

Fluorescence image of a coronal mouse brain section

The subthalamic nucleus, decomposed

Using spatial and single-cell transcriptomics we have identified molecularly distinct subpopulations within the rodent and primate STN and para-STN. Cross-species analyses reveal mRNA patterns unique to primate STN and directly relevant to neuropsychiatry and Parkinson's disease.

Selected references

· Wallén-Mackenzie et al., Communications Biology (2020)
· Prasad & Wallén-Mackenzie, Communications Biology (2024)

STN in motor control, aversion and avoidance

Optogenetic activation and silencing of defined STN subpopulations in freely-behaving mice has revealed roles beyond classical motor gating — including aversive learning, behavioural avoidance and reward-related processing.

Selected references

· Guillaumin et al., Brain Research (2021)
· Serra et al., Cell Reports (2023)

Dopamine neurons speak more than one language

A substantial fraction of midbrain dopamine neurons co-release glutamate via VGLUT2. We dissect how this co-transmission shapes mesoaccumbal and mesocortical signalling, growth and survival of dopamine neurons, and behavioural responses to psychostimulants and natural reward.

Selected references

· El Mestikawy, Wallén-Mackenzie et al., Nat Rev Neurosci (2011)
· Papathanou et al., Front Neural Circuits (2018)

Translational implications

Our work informs the development of next-generation deep brain stimulation targets, models of 6-OHDA-induced Parkinsonism, and the search for molecular handles on substance use disorder and neuropsychiatric symptoms of DBS.

Selected references

· Ricci et al., Neuropharmacology (2024)
· Guillaumin et al., Scand J Lab Anim Sci (2022)