Rollik, Lars Björn; (2024) Mapping function to pathways in the external globus pallidus. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The ability of animals to learn and execute action-outcome associations is crucial for survival, requiring the intricate interplay of numerous behavioral variables. These include the motivation to act, the selection and evaluation of actions, among others. The basal ganglia, a group of subcortical brain nuclei, have been established as critical for the learning and performance of these associations. However, the mapping of behavioral variables onto specific basal ganglia pathways remains incompletely understood. This thesis addresses this gap, focusing on the external globus pallidus (GPe), a core nucleus of the basal ganglia noted for its recent discovery of diverse genetic and projection populations. This work reveals how specific dimensions of behavior are encoded in distinct functional popula- tions within the GPe. Key findings include the identification of neuronal populations encoding movement or decision variables, such as right action values, as well as total and relative value. Utilizing optogenetic identification paired with local and antidromic stimulation, the functional representations of specific populations such as GPe-PV+ and GPe-PV+→GPi were explored. Subsequent investigation into the structural composition of the GPe aimed to elucidate the source of its functional heterogeneity. Employing single molecule FISH for gene markers, novel fea- tures in the organization of gene populations were identified. Concurrent multi-CTβ tracing revealed overlap between projections to multiple GPe downstream targets. To determine if the separation of functional and structural groups is reflected in their input connectivity, rabies input tracing was utilized. This revealed largely distinct input networks for GPe-PV+→GPi and GPe- PV−→GPi populations, characterized by more motor or limbic dominated inputs, respectively. Collectively, these findings contribute a new level of resolution and detail in the understanding of the GPe’s role in action-outcome associations, providing a framework for future exploration of how the brain implements these critical processes through basal ganglia pathways.

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