Souvenir (mémoire) | EPFL Graph Search

Un souvenir est quelque chose dont on se remémore, un élément de la mémoire. Paul Valéry Pour René Descartes, la description des mécanismes psychologiques permet de définir certaines de nos facultés. Ainsi le souvenir des choses matérielles est-il la conservation de certaines traces de mouvements provoqués dans notre cerveau. De même, l'imagination ne s'explique que par des mouvements corporels joints à une certaine activité de l'âme. Seule la pensée est active, en ce sens qu'elle n'a pas besoin de mouvements matériels : selon Descartes, la pensée est possible sans la perception et sans l'imagination. Dans le film de science-fiction "The Island" (2005), des clones créés adultes et maintenus en isolation hors du monde dans une base souterraine se découvrent des compétences et souvenirs appartenant à leurs modèles originaux. Ces compétences et souvenirs se transmettraient génétiquement, ce qui correspond à ce que Carl Gustav Jung envisageait pour son inconscient collectif. L

Where does the engram come from? Study of prefrontal cortex inputs during memory consolidation

Lucie Pauline Dixsaut

The formation and storage of memories has been under deep investigation for several decades. Nevertheless, the precise contribution of each brain region involved in this process and the interplay between them across memory consolidation is still largely debated. Although memory encoding requires the hippocampus (HPC), it is becoming apparent that other brain regions are also important in early phases of memory formation, such as the medial prefrontal cortex (mPFC). In addition, engram cells have been found in the mPFC at memory encoding: these cells represent a close approximation of the "memory trace" insofar as they are activated at the time of learning, as they undergo enduring molecular modifications after learning, and as their reactivation drives memory recall. In contrast to HPC engram cells, mPFC engram cells are thought to be kept silent during a recent recall and until the memory is fully consolidated, becoming active only at remote recall. To explain the dynamics of these mPFC engram cells, we hypothesized that inputs to the mPFC could be differentially activated over the course of memory consolidation.We first determined that the prelimbic cortex (PL), a subregion of the mPFC, was specifically activated during the encoding phase of a fear memory in mice by measuring the expression of the Immediate Early Gene cFos, transcribed upon neuronal activation. We then traced the inputs of PL cells that were active during encoding, the putative PL engram cells, in order screen for relevant connections for further investigations. To achieve this, we used an activity-dependent monosynaptic retrograde tracing method based on rabies tracing. Then, to determine the activation patterns of these specific PL inputs, we measured their activity throughout consolidation of a contextual fear memory using an unbiased retrograde tracer coupled with cFos immunostaining. We further tested their functional relevance by chemogenetically inhibiting these projections during the different learning phases. This approach confirmed the roles of the Entorhinal Cortex and the Basolateral Amygdala inputs during the encoding phase of a fear memory to later recall remote memories. In addition, we found that the Claustrum (CLA) to PL projection was also required during the encoding phase, but to recall recent memories specifically. Moreover, the Insular Cortex (INS) to PL projection was necessary during recent recall. Eventually, we observed that the CLA and INS manipulations led to a modification of PL engram cells reactivation during recent recall.Overall, our results suggest that there is a functional shift in PL inputs during the course of memory consolidation, which is also impacting how PL engram cells are reactivated. In addition, we observed that the activity of PL inputs is part of a broader brain network, both through the presence of axon collaterals targeting other brain regions and by the existence of parallel and perhaps redundant pathways that could ensure efficient memory consolidation.Collectively, our data help to further refine the working model of memory formation by deciphering the interplay between brain regions during the process of systems consolidation of a fear memory, and open several questions for future investigations.

EPFL2022

An insular cortex - lateral amygdala network in fear learning

Shriya Palchaudhuri

Animals are capable of evaluating sensory cues for possible threats and adapting their behaviours accordingly. Fear learning is an evolutionarily conserved behaviour crucial for animal survival, during which sensory percepts with a negative reinforcing quality, also called unconditioned stimuli (US), influence the valence of initially neutral sensory cues (conditioned stimulus, CS). The lateral amygdala (LA) is thought to integrate information about sensory cues like tones (the CS), and information about primary reinforcers like painful stimuli (the US). Nevertheless, synaptic afferents to the LA and upstream brain areas remain understudied in fear learning. The posterior insular cortex (pInsCx) has been shown to project to the LA and is known to be a multimodal sensory area which processes auditory, somatosensory-nociceptive, and interoceptive information, making it an interesting brain area with a putative role in fear learning. My PhD thesis therefore aimed to investigate a possible connection from the pInsCx to the LA, and the role of this pathway in the fear learning circuitry. I first used anatomical anterograde and retrograde tracing strategies in the mouse to study the afferents to the LA. Besides previously known inputs, I found that the granular (GI) and the dysgranular (DI) areas of the pInsCx strongly project to the anterior LA. With optogenetically-assisted circuit mapping (OACM), I found a glutamatergic monosynaptic connection from the pInsCx to LA principal neurons that, in agreement with the anatomical findings, was localized more to the anterior LA. In comparison, a well-studied auditory thalamic (MGm/PIN) input was localized more to the posterior LA. Despite this regional input specificity, ~30% LA principal neurons received projections from both areas. Thus, in the first part, using anatomical tracing and OACM, I have unambiguously shown a robust functional excitatory connection from the pInsCx (GI/DI) to the LA.In the second part of my thesis, I aimed to characterize the role of the pInsCx and the pInsCx-LA pathway in fear learning. Using archaerhodopsin-mediated optogenetic inhibition, I found that silencing of footshock-driven activity of pInsCx neurons in-vivo, partially blocks auditory-cued fear memory. These results were also supported by chemogenetic silencing of the pInsCx during the training day, which led to a modest impairment of fear retrieval a day later. Next, to investigate the role of the pInsCx-LA projection more specifically, I used a retrograde expression approach to silence LA-projectors during the footshock, which again, suppressed fear memory one day later. In further ex-vivo experiments, I found that EPSCs at the pInsCx-LA connection exhibited an increased AMPA/NMDA ratio following fear learning, indicating that plasticity occurs at this pathway during fear learning. Finally, miniature microscopic Ca2+ imaging of LA neurons combined with halorhodopsin-mediated axon inhibition, showed that the pInsCx-LA excitatory synapse contributes to transmitting footshock information to a sub-population of LA neurons. This study unravels the relationship between two serial nodes, the pInsCx and the LA, in the fear learning network. Thus, the pInsCx-LA connection is a novel pathway in auditory-cued fear memory that is strengthened with learning and that partly provides aversive information to the amygdala.

EPFL2022

Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation

Lucie Pauline Dixsaut, Johannes Gräff

Memory formation and storage rely on multiple interconnected brain areas, the contribution of which varies during memory consolidation. The medial prefrontal cortex, in particular the prelimbic cortex (PL), was traditionally found to be involved in remote memory storage, but recent evidence points toward its implication in early consolidation as well. Nevertheless, the inputs to the PL governing these dynamics remain unknown. Here, we first performed a brain-wide, rabies-based retrograde tracing screen of PL engram cells activated during contextual fear memory formation in male mice to identify relevant PL input regions. Next, we assessed the specific activity pattern of these inputs across different phases of memory consolidation, from fear memory encoding to recent and remote memory recall. Using projection-specific chemogenetic inhibition, we then tested their functional role in memory consolidation, which revealed a hitherto unknown contribution of claustrum to PL inputs at encoding, and of insular cortex to PL inputs at recent memory recall. Both of these inputs further impacted how PL engram cells were reactivated at memory recall, testifying to their relevance for establishing a memory trace in the PL. Collectively, these data identify a spatiotemporal shift in PL inputs important for early memory consolidation, and thereby help to refine the working model of memory formation.

2022

Where does the engram come from? Study of prefrontal cortex inputs during memory consolidation

Lucie Pauline Dixsaut

EPFL2022

An insular cortex - lateral amygdala network in fear learning

Shriya Palchaudhuri

EPFL2022