Memory formation

…work provides crucial insights into memory formation mechanisms at the synaptic level, with implications for understanding anxiety disorders and developing targeted interventions. Presented by Dr. Kenneth Hayworth, this journal club will explore

…activity may play a critical role in memory formation. However, the specific neural mechanisms that a

The brain continuously encodes new information as memories. At the synaptic level, memory formation is enabled by adjusting connections between activated excitatory neurons in the cortex, with mirroring inhibitory activity ensuring stable storage. Particularly, synaptic plasticity occurs as memory reactivation takes place during sleep, contributing to increased memory stability. However, the mechanism by which reactivation mediates plasticity to balance network currents for stable memory storage remains unclear. Here, we investigated whether a newly proposed form of codependent plasticity coul

Episodic memories are crucial elements that determine our sense of identity. Episodic memory formation is mostly dependent on the proper function of the hippocampus. However, mechanisms of episodic memory formation, maintenance and retrieval are only beginning to be elucidated. One of the leading scientific theories about the hippocampal role in memory is indexing theory. This concept builds on the premise that hippocampal neurons are multi-synaptically bi-directionally linked with sensory and associative cortical regions. Nevertheless, it is not clear if cortical reinstating occurs on a neuro

The formation of new memories requires the hippocampus, a brain region which exhibits high levels of structural plasticity. Within the dorsal hippocampal CA1, specific interneuron subtypes synapse onto specific subcellular compartments of Pyramidal Neurons (PNs) such as dendrites, soma and axon initial segment (AIS) thus shaping the cellular computations underlying memory formation. Yet, very little is known about the long-term structural dynamics of these compartmentalized inhibitory synapses on PNs and their link to learning.To address these outstanding questions, we used longitudinal in viv

Memories that are frequently revisited are easy to recall. In line with this observation, experimental evidence shows that familiar items involve larger hippocampal representations than less familiar ones. Here we developed a computational modeling approach, based on a dynamic attractor network model, to show how hippocampal neural assemblies may evolve differently, depending on the frequency of presentation of the stimuli (Boscaglia et al., 2023). Specifically, we built a dynamic attractor network model starting from a standard rate attractor model to which we added an online Hebbian learning

…is an m6A eraser that plays a role in memory formation in the brain. Our study aimed to investigate FTO's role in neurons and the modulation of its expression. We found that FTO is widely expressed in the mouse brain and increases d

Synaptic plasticity is a key process for brain function and memory formation. This depends on the ability of neurons to remodel their synaptic proteomes with high temporal and spatial resolution, promptly delivering and degrading the right proteins at the correct locations. Decades of work have shown that local protein synthesis at synapses is one of the mechanisms that enables remodeling of the local proteome. In vitro and ex vivo studies, mainly focusing on the hippocampus, have shown that neurons locally translate thousands of mRNAs, and that this process is required for several forms of lo

…understand their contributions to memory formation. We first generated a comprehensive single-cell RNA sequencing dataset of the telencephalon of adult zebrafish and mapped the diversity of neuronal cell types to anatomical brain areas. Gene expression data of G-protein coupled receptors were mined to embed individual cell types in neuromodulatory networks, allowing inference about which modu

Regulation of local protein synthesis is a critical aspect of synaptic plasticity and memory formation. Dendritic protein synthesis can be rapidly downregulated by microRNAs in conjunction with the RNA-induced silencing complex (RISC), of which Argonaute-2 (Ago2) is the core component. We previously demonstrated that NMDAR stimulation in vitro induces Ago2 phosphorylation at S387, which downregulates Limk1 expression via miR-134 as a result of increased binding of phosphorylated Ago2 to Limk1 mRNA. To explore the role of Ago2 S387 phosphorylation in vivo, we generated an Ago2S387A/S387A (phosp

It is widely accepted that experience-dependent plasticity is required for memory formation. However, underlying transcriptional and epigenetic changes are poorly understood.This project aims to deepen our understanding of the gene regulatory dynamics underpinning memory formation and how it is orchestrated with synaptic plasticity.To this end, we first characterized the immediate early genes (IEGs) and the secondary response genes (SRGs) at several time points after aversive learning from FACS-isolated cFOS-expressing mouse amygdalar nuclei. We performed RNA-seq to investigate the experience-

…such as sensorimotor integration and memory consolidation. The primary goal is to unravel the intricate information transfer mechanism between the MS and the hippocampus during memory formation, with a particular focus on the involvement of MS neurons in both hippocampal theta wave and ripple generation.To achieve this goal, a patch-clamp methodology was used for in vivo recording of MS neuronal activity. This approach was designed

Although changes in synaptic efficacy are widely thought to be a substrate for memory storage in the brain, the rules of synaptic plasticity are difficult to assess in vivo and thus remain unclear. We considered the dynamics of hippocampal representations as an indirect indicator of ongoing plasticity during memory formation and familiarization. Using calcium imaging data from mice navigating virtual tracks, during which CA1 or CA3 neurons were recorded, we tracked the evolution of the spatial modulation of their activity (place fields) lap by lap. During exploration of a novel environment, 50

Synaptic plasticity is known to be a key player in the brain’s life-long learning abilities. However, due to experimental limitations, the nature of the local changes at individual synapses and their link with emerging network-level computations remain unclear. In theoretical work, synaptic plasticity is often modelled with unsupervised local plasticity rules. However, deriving a complete set of functional plasticity rules analytically will require divine intuition and numerous assumptions. Here, we approach the problem numerically. We show how to deduce plasticity rules in silico with supervi

Dendrites are thin processes that extend from the cell body of neurons, the main computing units of the brain. The role of dendrites in complex brain functions has been investigated for several decades, yet their direct involvement in key behaviors such as for example sensory perception has only recently been established. In my presentation I will discuss how computational modelling has helped us illuminate dendritic function. I will present the main findings of a number of projects in lab dealing with dendritic nonlinearities in excitatory and inhibitory and their consequences on neuronal tun

…the molecular mechanisms underlying memory formation (e.g., using state-of-the-art molecular and cell-specific genetic approaches). Learning and memory disorders can strike the brain during development (e.g., Autism Spectrum Disorders and Down Syndrome), as well as during adulthood (e.g., Alzheimer’s disease). We are interested in understanding the specific circuits and molecular pathways that are primarily targeted i

…the neural circuit underlying memory formation in the neocortex is the distributed nature of the resulting memory trace throughout the cortex. Here, we used a new behavioral paradigm that enabled us to generate memory traces in a specific cortical location and to specifically examine the mechanisms of memory formation in that region. We found that medial-temporal inputs arrive in neocortical layer 1 where the apical dendrites of cortical pyramidal neurons pre

The hippocampus is implicated in memory formation, and neurons in the hippocampus take part in replay sequences, time-compressed reactivations of trajectories through space the animal has previously explored. These replay sequences have been proposed to be a form of memory for previously experienced places. I will present work exploring how these replays appear and change with experience. By recording from large ensembles of hippocampal neurons as rats explored novel and familiar linear tracks in various experiments, we found that hippocampal replays appear after a single experience and slow d

…studying areas of the brain linked to memory, the hippocampus and associated sections of cortex – by recording the activity of neurons in these areas we can visualise and hopefully understand the processes the trigger memor