To test our hypotheses, we conducted electrochemical measurements with real-time resolution simultaneously in limbic, associative, and sensorimotor aspects of the striatum to assess regional coordination of dopamine release in behaving animals, supported by rabies virus-mediated anatomical circuit mapping and in-vivo optogenetics in transgenic rats. Our results demonstrate that reward-seeking-related dopamine release into limbic, associative, and sensorimotor regions of the striatum are much more heterogeneous in its specific signal features within regions and less coordinated in its occurrence between regions than commonly assumed. Our work answers long-standing questions in the field about whether limbic, associative, and sensorimotor domains communicate with each other via dopamine-centric loop projections, and whether such inter-region coordination is of importance for the automation of action sequences (i.e. habit formation). In contrast to previous assumptions, dopamine signaling in the associated striatum (DMS), but not the sensorimotor striatum (DLS), is at the center of loop circuitry and crucial for the automation of behavior.
In this project, we set out to decipher a hierarchical organization of neural circuits potentially responsible for habit formation by investigating the functional connectivity of basal-ganglia networks involved in the coordination of dopamine signaling. In this context, we made several significant achievements:
1) We identified and demonstrated the existence of a complex neuroanatomical organizational principle in rats that was known to exist in primates only (inter-species confirmation), and, for the first time in any species, we provided functional evidence to verify this organizing principle.
2) We extended and updated this organizational principle by finding bi-directional connectivity instead of only uni-directional information flow through the anatomical structure.
3) We identified dopamine release in the so-called associative aspects of the striatum as at the center of habitual behavioral performance. This striatal region was previously only thought of as important for the control of flexible, goal-directed behavior (the opposite of habitual behavior). This new insight challenges the current beliefs in our field of research and may induce a paradigm shift.
