Biology subjects

Ojea Ramos, S.

Publications and source records attributed to Ojea Ramos, S..

6 recordsLinked to original sources

bioRxiv2026

The pERKs of Temporal Order Memory in mice

Temporal Order Memory (TOM), the ability to discriminate between events according to when they occurred, is a key component of episodic-like memory. Understanding the molecular mechanisms that support temporal memory requires behavioral approaches capable of capturing the continuous dynamics of natural exploration. Despite extensive evidence implicating the prefrontal cortex (PFC) in temporal memory, the intracellular signaling mechanisms supporting temporal order discrimination remain poorly understood. Here, we combined high-resolution automated behavioral phenotyping with molecular analyses to characterize the behavioral and signaling dynamics underlying TOM in m|ice. Mice were trained in a spontaneous object-recognition TOM task and tested after short-term (3 h) or long-term (24 h) retention intervals. Exploration was quantified using an artificial intelligence-based behavioral analysis pipeline that enables continuous and unbiased assessment of object exploration. Phosphorylation of extracellular signal-regulated kinase 2 (ERK2) and expression of the ERK phosphatase MKP3/DUSP6 were analyzed in the PFC and hippocampus (HIP) following habituation, a single training session, or two sequential training sessions. Additionally, a Temporal Novel Object Recognition (TeNOR) protocol was used to evaluate the integrity of memory traces. Mice displayed robust TOM performance across sexes and retention intervals. Molecular analyses revealed no significant changes in hippocampal ERK signaling, whereas the cytosolic fraction of the PFC exhibited dynamic, experience-dependent modulation of ERK2 phosphorylation. A single 15-minute training session induced a transient increase in ERK2 activation, while a second session 45 minutes later actively suppressed this peak. This rapid molecular reset was accompanied by increased MKP3 expression, suggesting the targeted recruitment of an active regulatory feedback mechanism. Continuous behavioral tracking further revealed temporal features of memory expression that were not captured by conventional summary measures; it identified an early, rapid decay of discrimination for older object memories in the TeNOR task, suggesting that TOM performance relies on resolving competitive retrieval between co-existing memory traces. Together, these findings identify dynamic ERK2-MKP3 signaling in the PFC as the molecular substrate upon which temporal discrimination can take place, and demonstrate how high-resolution phenotyping in naturalistic behavioral paradigms can reveal mechanistic links between intracellular signaling and the temporal organization of experience.

neuroscience↗

bioRxiv2025

RAINSTORM: Automated Behavioral Analysis for Mice Exploratory Behavior Using Artificial Neural Networks.

Rodent exploratory behavior is widely used for assessing cognitive function. RAINSTORM -- Real and Artificial Intelligence for Neuroscience - Simple Tracker for Object Recognition Memory -- is a versatile tool designed to streamline the analysis of such behaviors in rodents. This pipeline integrates manual behavioral scoring, geometric analysis, and artificial intelligence (AI)-powered behavioral labeling, offering reproducible, scalable, and efficient evaluation methods. RAINSTORM processes raw positional data and automates the identification of exploratory behaviors, providing insights into memory performance. This tool is designed to learn from the labeling criteria of one or more experimenters by capturing the different aspects of expert opinion and reducing subjective bias in subsequent scoring procedures. The experimenter can go from unprocessed pose estimation data (obtained through open source software such as DeepLabCut) to accurate exploration patterns in a matter of minutes. By optimizing the analysis process, RAINSTORM significantly enhances the reliability and efficiency of behavioral research. RAINSTORM has become a robust methodology for assessing recognition memory in rodents by accurately quantifying exploration times for familiar and novel objects. It has since been extended to include (but not limited to) a wider range of exploratory behaviors. The software is readily applicable to other experimental designs that rely on quantifying exploration in mice, such as Social Preference and Object Pattern Separation, among others.

animal behavior and cognition↗

bioRxiv2024

Role of ERK2 dimerization in synaptic plasticity and memory

Extensive research has focused on extracellular-signal regulated kinase (ERK) 1/2 phosphorylation across various memory and plasticity models. However, the precise mechanisms linking ERK activity to memory stabilization and restabilization are still poorly understood, and the role of ERK1/2 dimerization remains unexplored. ERK dimerization is essential for the binding and activation of cytoplasmic targets, many of which are involved in memory and plasticity. In this study, we investigated the role of ERK2 dimerization in long-term memory and synaptic plasticity. We found that reactivation of a weak inhibitory avoidance (wIA) memory led to a significant reduction in hippocampal ERK2 dimerization. Furthermore, intrahippocampal infusion of DEL-22379 (DEL), an ERK dimerization inhibitor, following memory reactivation had a bidirectional effect: it blocked the reconsolidation of a strong inhibitory avoidance (sIA) memory but enhanced the reconsolidation of a wIA memory. Moreover, DEL administration blocked hippocampal ERK2 dimerization in vivo and impaired high-frequency stimulation-induced long-term potentiation (LTP) in hippocampal slices. These findings demonstrate that ERK2 dimerization occurs in the intact mouse nervous system and plays a pivotal role in plasticity and memory. While further research is needed, this study highlights the relevance of ERK dimerization in these processes.

neuroscience↗

bioRxiv2024

Delving into the claustrum: insights into memory formation, stabilization and updating in mice

The claustrum is a brain structure that remains shrouded in mystery due to the limited understanding of its cellular structure, neural pathways, functionality and physiological aspects. Significant research has unveiled connections spanning from the claustrum to the entire cortex as well as subcortical areas. This widespread connectivity has led to speculations of its role in integrating information from different brain regions, possibly contributing to processes such as attention, consciousness, learning and memory. Our working hypothesis posits that claustrum neural activity contributes to the formation, stabilization and updating of long-term memories in mice. We found evidence in CF-1 mice of a decline in behavioral performance in an inhibitory avoidance task due to intra-claustral administration of 2% lidocaine immediately after a training session or memory recall. Nevertheless, this does not seem to be the case for the acquisition or retrieval of this type of memory, although its neural activity is significantly increased after training, evaluated through c-Fos expression. Moreover, inhibition of the claustrums synaptic activity appears to impair stabilization but not the acquisition or retrieval of an unconditioned memory formed in a nose-poke habituation task.

neuroscience↗

bioRxiv2023

Long-term structural plasticity of hippocampal dendritic spines following contextual fear memory reactivation

Dendritic spines are plastic structures exhibiting a high degree of morphological variability. Certain morphometric parameters, such as volume, positively correlate with the strength of the synapse in which they participate. Memories, too, are subject to change over time and with experiences. In particular, the presence of a reminder of a learning event can trigger the labilization of the memory trace, followed by a re-stabilization process termed reconsolidation. The underlying mechanisms behind the labilization/reconsolidation processes are of great interest, as they are thought of as possible targets for the treatment of post-traumatic stress disorders. Dendritic spines have long been considered the physical sites for memory formation and storage. Our work aimed at studying the long-term spine morphological plasticity associated with labilization/reconsolidation in the dorsal hippocampus, a brain region relevant for the formation of contextual memories. Our results suggest that labilization/reconsolidation does not affect spine density, but rather induces changes in spine morphology. Furthermore, we show that some of these changes are prevented by the inhibition of the transcription factor NF-{kappa}B inhibition. Finally, we found that NF-{kappa}B negative modulation also affects spine morphology in animals that were not exposed to recall but have undergone the training session, suggesting that there may be a late surge of NF-{kappa}B activity resulting from the consolidation itself.

neuroscience↗

bioRxiv2020

Two spaced training trials induce associative ERK-dependent long- term memory in Neohelice granulata.

Memory formation depends upon several parametric training conditions. Among them, trial number and inter-trial interval (ITI) are key factors to induce long-term retention. However, it is still unclear how individual training trials contribute to mechanisms underlying memory formation and stabilization. Contextual conditioning in Neohelice granulata has traditionally elicited associative long-term memory (LTM) after 15 spaced (ITI = 3 min) trials. Here, we show that LTM in crabs can be induced after only two training trials by increasing the ITI to 45 min (2t-LTM) and maintaining the same training duration as in traditional protocols. This new LTM observed was preserved for at least 96 h, exhibited protein synthesis dependence during consolidation and reconsolidation as well as context-specificity. Moreover, we demonstrate that 2t-LTM depends on inter-trial and post-training ERK activation showing a faster phosphorylation after the second trial compared to the first one. In summary, we present a new training protocol in crabs with reduced number of trials that shows associative features similar to traditional spaced training. This novel protocol allows intra-training manipulation and the assessment of individual trial contribution to LTM formation.

neuroscience↗