Defense in english
Title
Determine how intrinsic excitability plasticity of defined neuronal engram ensembles in the anterior cingulate cortex influences the precision of remote memory
Abstract
Associative memories are gradually stored and stabilized within the neocortical circuits during the course of systems-level memory consolidation. The anterior cingulate cortex (ACC) is assumed to play a critical role in remote but not recent contextual fear memory formation. Besides synaptic plasticity, intrinsic plasticity also crucially contributes to learning and memory, especially in the dynamic aspect of memory like allocation and consolidation. A plastic change in the intrinsic excitability of engram ensembles following a learning experience provides an attractive permissive mechanism for forming a memory trace. However, little is known about learning-induced intrinsic excitability plasticity in the neocortex and its functional relevance for remote contextual fear memory.
This thesis investigated the intrinsic excitability change of putative ACC engram ensembles induced by contextual fear conditioning and how the chemogenetic modification of excitability in these neurons during the memory consolidation phase could influence the precision of remote memory.
Firstly, we used a c-fos dependent labeling system, TetTag mice and doxycycline, combined with virally encoded tools enabling the identification and visualization of ACC neurons engaged explicitly in the encoding phase of contextual fear conditioning. Also, the organization of these engram neurons across layers within the ACC was compared. Next, by using ex vivo whole-cell recordings from putative engram neurons of acute ACC brain slices, we characterized the intrinsic properties of these neurons following contextual fear conditioning. Finally, we used a chemogenetic approach, based on excitatory or inhibitory DREADD (designer receptor exclusively activated by designer drugs) expressed in ACC engram ensembles to assess the functional role of intrinsic excitability plasticity in different phases for memory formation and precision. Furthermore, we designed memory interference experiments to examine the effect of suppressing the ACC engram ensembles in remote memory precision with DREADD.
Together, our study suggests an essential role of intrinsic excitability plasticity in the assumed ACC engram ensembles during the early phase of contextual fear memory consolidation for remote memory formation and precision.
Keywords:
Intrinsic excitability plasticity, Engram ensembles, Remote memory, Anterior cingulate cortex.
Jury
- Christophe MULLE (Président/ Examinateur)
- Gisella VETERE (Rapporteur)
- Matthew NOLAN (Rapporteur)
- Lisa ROUX (Invité)
- Andreas Frick (Directeur de thèse)
Liangying ZHU
Team Frick
Neurocenre Magendie
Thesis supervisor: Andreas Frick