Methods

A toolkit for circuit-level molecular anatomy.

Our experimental approach combines genetic access to defined cell types, viral circuit tracing, optogenetic perturbation and high-resolution imaging — all anchored in carefully controlled mouse behaviour.

Whole-brain fluorescence image of neural projections and tracts
01

Viral vector tracing

AAV and rabies-virus tracing in Cre-driver mouse lines to map afferent and efferent connectivity of molecularly defined STN and dopamine subpopulations.

02

Optogenetics and chemogenetics (DREADDs)

Cell-type-specific activation and silencing using optogenetics and chemogenetic DREADDs (Gs, Gq, Gi, KORD), enabling precise, reversible control of genetically defined neurons.

03

IHC and fluorescent in situ hybridisation (FISH)

Multiplexed FISH with post-FISH immunofluorescence (ORAMACELL protocols) to co-detect mRNA and protein in fresh-frozen sections, enabling identification of rare neuronal subtypes.

04

Behavioural neuroscience

Quantitative motor, motivational and aversive learning assays in mice, including operant behaviour paradigms and the 6-OHDA model of Parkinson's disease with a refined survival protocol.

05

Confocal & widefield microscopy

Image acquisition and quantitative cell counting of FISH-labelled cells across rostro-caudal extents of the STN, midbrain and forebrain.

06

Spatial and single-nuclei transcriptomics

Cross-species spatial transcriptomics and snRNA-seq to compare subthalamic and para-subthalamic populations between mouse, non-human primate and human tissue.

07

Electrochemical detection (amperometry)

Amperometric biosensors to measure acute neurotransmitter and metabolite release in vivo: dopamine, glutamate, acetylcholine, GABA, lactate and pyruvate.

08

Artificial intelligence

Custom algorithms for automated cell quantification of microglia and TH cells, plus 4D movement analysis for rats and mice.