Biology subjects

Feld, M.

Publications and source records attributed to Feld, M..

5 recordsLinked to original sources

bioRxiv2026

HDAC3 inhibitor RGFP966 acts on the NF-kB pathway and enhances memory persistence in a biphasic manner

Nearly five decades ago, it was first observed that long-term memory consolidation requires waves of transcriptional activity and protein synthesis, with the first two waves occurring within hours after learning. While numerous studies have examined the effects of protein synthesis inhibitors, how specific epigenetic regulators contribute to these waves remains poorly understood. Here, we aimed to determine whether HDAC3, a key modulator of memory, is involved in memory consolidation at these two time points through its potential relationship with the transcription factor NF-kB, one of its deacetylation targets and a critical player in memory formation. Pharmacological inhibition of HDAC3 with RGFP966, either immediately or 6 hours after training, enhanced memory persistence in the NOR task in mice. Conversely, inhibition of NF-kB with BAY 11-7082 impaired memory at the same time points. Moreover, RGFP966 injection increased the nuclear proportion of NF-{kappa}B in the CA1 region of the hippocampus, suggesting that HDAC3 inhibition is associated with changes in NF-kB nuclear localization. To our knowledge, this study provides the first in vivo evidence that HDAC3 inhibition is associated with altered NF-kB localization during memory consolidation, extending previous observations from cell culture and electrophysiological studies in brain slices. Although these findings support a functional association between HDAC3 inhibition and NF-kB signaling during consolidation, further experiments will be required to determine whether this relationship is mechanistically causal.

neuroscience↗

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↗

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↗