Biology subjects

Alevi, D.

Publications and source records attributed to Alevi, D..

3 recordsLinked to original sources

bioRxiv2026

Memory consolidation and representational drift

Memory consolidation is the process by which temporary, malleable memories are transformed into more stable, longer-lasting forms. On a coarse anatomical scale, consolidation redistributes memories in the brain, but it remains poorly understood how these changes manifest themselves on the finer, cellular scale of neuronal engrams and how they relate to the cognitive level. In this study, we developed a phenomenological model of engram dynamics under systems consolidation. The model describes consolidation as a brain-wide phenomenon, where memories deterministically follow a trajectory through a space of patterns distributed among brain regions. It captures a broad range of features of memory consolidation, including selective consolidation, semantization, and power-law forgetting. In the model, consolidation is accompanied by population-level changes in neuronal representations that resemble the widely observed phenomenon of representational drift. When only a subset of neurons is observed, the deterministic dynamics of the model can appear stochastic, and a readout of task features deteriorates over time even when a stable readout exists for the full system. Our model offers a dynamical systems perspective on memory consolidation as a distributed process, moving beyond the classic region-centered view, and provides a functional interpretation of drift as a means of redistributing engrams for improved memory retention.

neuroscience↗

bioRxiv2025

Calbindin-containing CA1 pyramidal cells support cognitive flexibility in spatial task in mice

The hippocampus, and particularly the dorsal CA1, is essential for spatial memory consolidation through sharp-wave ripple events (SWRs) that enable the transfer of information to cortical areas. Within the dorsal CA1, distinct pyramidal cell sub-populations of the deep and superficial layer may play distinct roles in the processing and updating of spatial information. Using a Cre-dependent mouseline, we were able to precisely target the superficial, Calbindin (CALB1+) PCs of the CA1. This allowed us to gain a deeper understanding of the connectivity of CALB1+ CA1 PCs to their SWR-propagating excitatory output partners within the Subiculum (SUB), the burst-firing SUB PCs and their functional relevance in spatial memory consolidation and recall. Retrograde rabies tracing revealed heterogeneous innervation of the VGlut2+ bursting PCs by both CA1 PC sub-layers, and showed that the majority of presynaptic inputs are located in the superficial CA1 PC layer. We were able to observe that this anatomically confirmed connection between CALB1+ CA1 PCs and both SUB PC subtypes is able to induce spiking more reliably in burst- than regular-firing SUB PCs. CNO-induced inhibition in a Barnes Maze task revealed that the experimental group showed reduced cognitive flexibility and were slower to adapt to re-location of the goal when CALB1+ CA1 PCs were inhibited during the recall (test), while both groups behaved similarly when consolidation was manipulated (training). Inhibition did not impact overall learning, strategy development or locomotor control. This suggests that CALB1+ CA1 PCs preferentially connect to bursting SUB PCs, and support cognitive flexibility needed to adapt to a changing environment, adding further proof to the functional relevance of laminar segregation of the CA1 and the hippocampus in spatial memory processes.

neuroscience↗

bioRxiv2020

Hebbian plasticity in parallel synaptic pathways: A circuit mechanism for systems memory consolidation

Systems memory consolidation involves the transfer of memories across brain regions and the transformation of memory content. For example, declarative memories that transiently depend on the hippocampal formation are transformed into long-term memory traces in neocortical networks, and procedural memories are transformed within cortico-striatal networks. These consolidation processes are thought to rely on replay and repetition of recently acquired memories, but the cellular and network mechanisms that mediate the changes of memories are poorly understood. Here, we suggest that systems memory consolidation could arise from Hebbian plasticity in networks with parallel synaptic pathways -- two ubiquitous features of neural circuits in the brain. We explore this hypothesis in the context of hippocampus-dependent memories. Using computational models and mathematical analyses, we illustrate how memories are transferred across circuits and discuss why their representations could change. The analyses suggest that Hebbian plasticity mediates consolidation by transferring a linear approximation of a previously acquired memory into a parallel pathway. Our modelling results are further in quantitative agreement with lesion studies in rodents. Moreover, a hierarchical iteration of the mechanism yields power-law forgetting -- as observed in psychophysical studies in humans. The predicted circuit mechanism thus bridges spatial scales from single cells to cortical areas and time scales from milliseconds to years. Author summaryAfter new memories are acquired, they can be transferred over time into other brain areas -- a process called systems memory consolidation. For example, new declarative memories, which refer to the conscious memory of facts and events, depend on the hippocampus. Older declarative memories, however, also rely on neocortical networks. The cellular mechanisms underlying such a transfer are poorly understood. In this work, we show that a simple and in the brain ubiquitous connectivity pattern, combined with a standard learning rule, leads to gradual memory transfer. We illustrate our proposed mechanism in numerical simulations and mathematical analyses. At the neurophysiological level, our theory explains experimental findings on memory storage in the hippocampal formation when specific pathways between neural populations are disrupted. At the psychophysical level, we can account for the power-law forgetting curves typically found in humans. A consequence of the proposed model is that consolidated memories can yield faster responses because they are stored in increasingly shorter synaptic pathways between sensory and motor areas. By giving a mechanistic explanation of the consolidation process, we contribute to the understanding of the transfer of memories and the reorganization of memories over time.

neuroscience↗