Search bioRxiv⌕ Search

Biology subjects

Fernandez-Ruiz, A.

Publications and source records attributed to Fernandez-Ruiz, A..

7 recordsLinked to original sources
bioRxiv2026

Dynamic shifts in brain criticality support cognitive processing

Systems operating near their critical point, or close to a transition between order and disorder, have computational advantages. In the case of neural networks, proximity to criticality is proposed to support optimal brain function. However, different cognitive processes rely on disparate computational demands. Using large-scale electrophysiological recordings in behaving rodents, we examined how critical dynamics in the hippocampus are regulated during learning and sleep-dependent memory consolidation. We found that operating near criticality enables learning by facilitating hippocampal coordination with input regions and maximizing flexibility of neural representations. In contrast, the hippocampal network shifts toward a more ordered, subcritical regime during sleep memory replay, and recovers its proximity to criticality through cholecystokinin interneurons-mediated inhibition. Overall, our findings provide a biophysical substrate for understanding how critical dynamics in neuronal networks can support a variety of brain functions. Importantly, our results suggest that optimal learning systems, whether biological or artificial, may require a dynamic regulation between flexible and rigid states, and can offer biophysical constraints to guide the design of Large Language Models (LLM) tuned to criticality.

neuroscience↗
bioRxiv2025

Large sharp-wave ripples promote hippocampo-cortical memory reactivation and consolidation

During sleep, ensemble activity patterns encoding recent experiences are reactivated in the hippocampus and cortex. This reactivation is coordinated by hippocampal sharp-wave ripples (SWRs) and is believed to support the early stages of memory consolidation. However, only a minority of sleep SWRs are associated with memory reactivation in the hippocampus and its downstream areas. Whether that subset of SWRs have specific physiological characteristics and directly contribute to memory performance is not known. We identified a specific subset of large SWRs linked to memory reactivation in both the hippocampus and prefrontal cortex (PFC) of mice, and found that their occurrence selectively increased during sleep following new learning. Closed-loop optogenetic SWR boosting during sleep was sufficient to enhance ensemble memory reactivation in hippocampus and PFC. This manipulation also improved subsequent memory retrieval and hippocampal-PFC coordination during waking, causally linking both phenomena to SWR-associated ensemble reactivation during sleep.

neuroscience↗
bioRxiv2025

A hippocampal population code for rapid generalization

Generalizing from experience and applying prior knowledge to new situations is essential for intelligent behavior. Traditional models attribute this generalization to gradual statistical learning in the neocortex. However, such a slow process cannot account for animals rapid generalization from limited experience. Here, we demonstrate that the hippocampus supports rapid generalization in mice by generating disentangled memory representations, where different aspects of experience are encoded independently. This code enabled the transfer of prior knowledge to solve new tasks. We identify specific circuit mechanisms underlying this rapid generalization. We show that the seemingly random changes in individual neuronal activity over time and across environments result from structured circuit-level processes, governed by the dynamics of local inhibition and cross-regional cell assemblies, respectively. Our findings provide computational and mechanistic insights into how the geometric structure and underlying circuit organization of hippocampal population dynamics facilitate both memory discrimination and generalization, enabling efficient and flexible learning.

neuroscience↗
bioRxiv2022

Hippocampo-cortical circuits for selective memory encoding, routing, and replay

Traditionally considered a homogeneous cell type, hippocampal pyramidal cells have been recently shown to be highly diverse. However, how this cellular diversity relates to the different hippocampal network computations that support memory-guided behavior is not yet known. We discovered that the anatomical identity of pyramidal cells is a major organizing principle of CA1 assembly dynamics, the emergence of memory replay, and cortical projection patterns. Segregated pyramidal cell subpopulations encoded trajectory and choice-specific information or tracked changes in reward configuration respectively, and selectively routed these representations to different cortical targets. Furthermore, distinct hippocampo-cortical assemblies coordinated the reactivation of complementary memory representations. These findings reveal the existence of specialized hippocampo-cortical subcircuits and provide a cellular mechanism that supports the computational flexibility and memory capacities of these structures.

neuroscience↗
bioRxiv2020

Subcircuits of deep and superficial CA1 place cells support efficient spatial coding across heterogeneous environments

The hippocampus is thought to guide navigation by forming a cognitive map of space. However, the behavioral demands for such a map can vary depending on particular features of a given environment. For example, an environment rich in cues may require a finer resolution map than an open space. It is unclear how the hippocampal cognitive map adjusts to meet these distinct behavioral demands. To address this issue, we examined the spatial coding characteristics of hippocampal neurons in mice and rats navigating different environments. We found that CA1 place cells located in the superficial sublayer were more active in cue-poor environments, and preferentially used a firing rate code driven by intra-hippocampal inputs. In contrast, place cells located in the deep sublayer were more active in cue-rich environments and expressed a phase code driven by entorhinal inputs. Switching between these two spatial coding modes was supported by the interaction between excitatory gamma inputs and local inhibition.

neuroscience↗
bioRxiv2020

Hippocampal CA2 ripples recruit social replay and promote social memory

The consolidation of spatial memory depends on the reactivation ( replay) of hippocampal place cells that were active during recent behavior. These reactivations are observed during sharp wave-ripples (SWRs), synchronous oscillatory events that occur during slow-wave sleep1-9 and whose disruption impairs spatial memory consolidation 4,6,7,9. Although the hippocampus encodes a wide range of non-spatial forms of declarative memory, it is not yet known whether SWRs are necessary for non-spatial memory. Moreover, although SWRs can arise from either the hippocampal CA38 or CA210 regions, the relative importance of these sources for memory consolidation is unknown. Here we examined the role of SWRs during the consolidation of social memory, the ability of an animal to recognize and remember a conspecific, focusing on CA2 because of its critical role in social memory11,12,13. We found that ensembles of CA2 pyramidal neurons that were active during social exploration of novel conspecifics were reactivated during SWRs. Importantly, disruption or enhancement of CA2 SWRs suppressed or prolonged social memory, respectively. Thus, SWR reactivation of hippocampal firing related to recent experience appears to be a general mechanism for binding spatial, temporal and sensory information into high-order memory representations.

neuroscience↗