Venue : centre Broca
Defense in english
Team : Computational and systems neuroscience (IINS)
Thesis directed by Dr HUMEAU Yann et Dr FRICK Andreas.
Title
Fear memory and the anterior cingulate cortex
Abstract
Memory allows animals and humans to use past experiences to direct future actions and adapt flexibly in changing environments. Modern neuroscience increasingly sees memory as a predictive system: one that detects patterns in experiences to anticipate upcoming events and prepare appropriate responses. This predictive ability depends heavily on the brain’s capacity to encode temporal structure, which not only shows what happened but also indicates when it is expected to occur. Thus, temporal information is a crucial part of memory that influences behavior across various species. Fear learning is a type of memory that provides a powerful framework for exploring temporal prediction. Contextual conditioning teaches animals that a context signals an upcoming unconditioned stimulus (US), such as a foot shock. Crucially, they learn the timing between multiple US presentations. This temporal map greatly influences the timing and strength of defensive responses like freezing. During recall, some animals freeze immediately upon entering the context, indicating a contextual approach, while others freeze later, aligning with the predicted US timing, suggesting a temporal strategy. These behavioral differences highlight the importance of temporal processing in fear memory and reveal underlying diversity in neural computations. Fear memories are stored in dispersed neural groups, also called “memory engrams,” which activate after the experience and during recall. Recall reopens the reconsolidation window when memories can be updated, strengthened, or erased. This process is especially important for cortical regions like the anterior cingulate cortex, which are repeatedly involved in expressing remote memory.
Recent research shows that cortical engrams change over days and months, and each recall can either stabilize or alter their activation patterns. The anterior cingulate cortex is part of the medial prefrontal cortex and serves as a key hub for integration tasks. However, its exact role in predicting dangers during natural behaviors is still not fully understood. Another open question is the role of US-responsive neurons in the ACC. This group of neurons (US1 responsive cells) shows strong responses specifically during the aversive event and may form part of the cortical component of the fear engram. Their reactivation during recent and remote recall could reveal how aversive memory traces change over time and whether recall episodes affect their stability. The dynamics of US-responsive ensembles in the ACC and their iv relationship to behavioral variability remain largely unexplored.
Finally, there are notable individual differences among animals in the timing of freezing during recall; some show early, contextdriven freezing, while others display delayed, temporally aligned freezing. Whether these behavioral differences relate to distinct patterns of ACC activity or US-ensemble reactivation remains unknown. My thesis addresses these gaps by combining longitudinal calcium imaging with detailed behavioral quantification to explore how the ACC encodes and updates temporal predictions of threat. It also examines how recall history influences ACC population dynamics, ACC-behavior coupling, and the stability of US-responsive ensembles by comparing animals that had a recent recall session in the shock-associated context to those that did not. Together, these analyses aim to clarify the role of the ACC in temporal prediction, fear regulation, and the long-term organization of aversive memory engrams.
Keywords: Anterior cingulate cortex (ACC), Calcium imaging, neuronal ensemble, Temporal
prediction
Jury
Dr.Aude Panatier, CNRS Researcher, Neurocentre Magendie ; Examiner
Dr.Julien Courtin, INSERM Researcher, Neurocentre Magendie ; Examiner
Dr.Philippe Isope, CNRS Research director, Université de strasbourg ; Rapporteur
Dr.Daniela Popa, INSERM Researcher, Institut de Biologie de l’école normale supérieur Paris ; Rapporteur