The role of the retrosplenial cortex in associative memory

Thesis

Encoding of episodic memories involves associating different features of the environment and experiences. Understanding how sensory-sensory associations are encoded would shed light on the basis of how events are stored in the brain.

The retrosplenial cortex (RSC) is known to reciprocally connect to the hippocampal formation and to sensory areas. Its connectivity suggests a role in both episodic and spatial memory processes. A role in the formation and storage of sensory associations might underlie these processes and is supported by RSC-lesion and -inactivation studies.

In this thesis, I use optogenetics to inactivate the RSC while mice perform various memory paradigms to clarify the function of this structure in encoding associations to support memory. Thus, I develop a sensory associative memory task in mice which allows me to test sensory-sensory associations. Developing, for the first time, an appetitive sensory preconditioning (SPC) paradigm in mice, failed to provide robust results. So, I chose an aversive SPC paradigm as the best way to probe neutral sensory associations in mice.

I show that while control mice successfully learned the preconditioned association in the task, precise closed-loop optogenetic disruption of the RSC when mice form associations between neutral stimuli reduces performance to chance levels. Moreover, I demonstrate that this disruption is independent of spatial confound.

Using the same technique to silence RSC activity during short-term or long-term spatial learning did not affect the formation and retrieval of memory, in contrast to previous studies.

Finally, in order to truly address the question of how sensory-sensory associations are formed, I present preliminary data of a calcium imaging study aimed at understanding the mechanisms by which these associations are formed in the RSC.

In summary, I established a new sensory preconditioning task for mice allowing us to timely probe associative memory between neutral stimuli. Optogenetic silencing of RSC demonstrate the necessity of the RSC in this type of memory and combined with future functional imaging studies will help understand how the brain forms neutral associations.

Authors: Bottura de Barros, A

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: associations; retrosplenial cortex; memory; optogenetics; behaviour
• Subjects: Neurosciences