ASSOCIATIVE INFORMATION FLOW THROUGH THE STRIATUM: A NOVEL HIGH-THROUGHPUT ANALYSIS OF INTRACELLULAR SIGNALLING DYNAMICS IN THE STRIATAL CONTINUUM DURING LEARNING

The striatal complex of the basal ganglia is a key locus in the mammalian brain where associative learning is encoded. Its distinctive cytoarchitecture—densely populated with a unique neuronal subtype exhibiting characteristic cellular specialisations—supports large-scale signal integration critical for learning. Although extensive work has described the dense excitatory and neuromodulatory inputs to the striatum, much less is known about how these diverse signals are encoded within, or communicated across, its functional domains.
The aim of this study was to establish and validate a high-throughput imaging and analytical framework for large-scale, single-cell mapping of learning-dependent intracellular signalling across the striatal continuum. To this end, we combined established associative learning paradigms with a novel transgenic construct to develop an image-analysis pipeline capable of tracking ERK activity dynamics—a key marker of learning-related plasticity—in individual D1-neurons (~10⁴ neurons/group) with unprecedented spatial resolution.
Across both Pavlovian and instrumental learning, our data show that striatal plasticity emerges as a flexible, topographically organised pattern reflecting contingency structure, sensory modality, behavioural demands, and individual strategy. Network-level analyses further reveal that adaptive behaviour is supported by dynamic reconfiguration of intrastriatal connectivity, enabling goal-directed control to be maintained despite altered contingencies, focal perturbations, or inter-individual variability. Together, these findings support functional models of striatal subregional organisation while providing novel insights into how plasticity propagates through the striatal network to support associative learning.