A novel paradigm to investigate the role of the retrosplenial cortex in spatial learning and memory in freely behaving mice

Loidolt, Annette (2025): A novel paradigm to investigate the role of the retrosplenial cortex in spatial learning and memory in freely behaving mice: Ob du wirklich richtig stehst, siehst du, wenn das Licht angeht. Dissertation, LMU München: Fakultät für Biologie

Abstract

Spatial cognition is vital for the survival of many species, enabling mice and other animals to navigate their environment, locate food resources, and escape from threats. Meanwhile, spatial learning and memory allow an individual to acquire, retain, and recall spatial information. The retrosplenial cortex (RSC) has recently gained attention for its role in spatial cognition and memory, integrating sensory and spatial signals. Despite extensive research on the neural circuits involved in spatial learning through employment of various spatial memory tasks, the specific contributions of the rodent RSC to spatial memory are not fully understood. This gap in knowledge emphasises the need for innovative behavioural paradigms to address previous spatial memory tasks’ limitations. In this thesis, I present a novel behavioural paradigm designed to explore the role of the RSC to spatial learning and memory. The task I developed investigates mechanisms of spatial memory formation, retrieval, and reversal learning in rodents, wherein mice learn the locations of hidden trigger zones within a circular arena. This spatial memory task stands out for its ability to track mice, their behaviour, and task performance in a three-dimensional environment without any physical constraints on head or body movement. This allows for naturalistic animal behaviour and the simultaneous use of portable neuronal recording devices during training. In this study, I identified key task metrics for quantifying behaviour in the spatial memory task, including error angles and active task engagement, to assess learning and task performance. Using these parameters, I demonstrate that the goal-directed navigational strategies employed by mice vary significantly whether they are guided by vision or memory. Specifically, mice resort to memory-guided navigation exclusively in the absence of visual landmark cues. Through manipulations of the external landmarks within the animals' environment during spatial memory training, I demonstrate that mice develop a comprehensive cognitive map of the arena and the surrounding space, using allocentric navigation strategies to locate previously learnt goal locations. The results of this study further show that mice can form robust allocentric spatial memories quickly and efficiently, even under conditions where RSC activity is inhibited. Chemogenetic experiments show that inactivating RSC neuronal activity does not impede the formation or retrieval of spatial memories in this task. Taken together, these findings highlight the effectiveness of this task for investigating allocentric spatial learning and memory in mice. Characterized by rapid acquisition of task proficiency, high trial rates, reliable memory formation and recall, brief pre-training periods, and unrestricted, natural mouse behaviour, this paradigm opens up new avenues for advanced research into the neural substrates of spatial learning and memory with broad applications in RSC research and beyond.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 24. April 2025
• 1. Bericht­erstatter:in: Bonhoeffer, Tobias