Biology subjects

Medina, C.

Publications and source records attributed to Medina, C..

7 recordsLinked to original sources

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↗

bioRxiv2022

Amount of Pannexin 1 in smooth muscle cells regulates sympathetic nerve induced vasoconstriction

Pannexin 1 (Panx1) forms high conductance channels that secrete ATP upon stimulation. The role of Panx1 in mediating constriction in response to direct sympathetic nerve stimulation is not known. Additionally, it is unknown how the expression level of Panx1 in SMCs influences a-adrenergic responses. We hypothesized that the amount of Panx1 in SMCs dictates the levels of sympathetic constriction and blood pressure. To test this hypothesis, we used genetically modified mouse models enabling expression of Panx1 in vascular cells to be varied. Genetic deletion of SMC Panx1 prevented constriction by electric field stimulation of sympathetic nerves. Conversely, over-expression of Panx1 in SMCs using a ROSA26 transgenic model increased sympathetic nerve-mediated constriction. Cx43 hemichannel inhibitors did not alter constriction. Next, we evaluated the effects of altered SMC Panx1 expression on blood pressure. To do this, we created mice combining a global Panx1 deletion, with ROSA26-Panx1 under the control of an inducible SMC specific Cre (Myh11). This resulted in mice that could express only human Panx1, only in SMCs. After tamoxifen, these mice had increased blood pressure that was acutely decreased by the Panx1 inhibitor spironolactone. Control mice genetically devoid of Panx1 did not respond to spironolactone. These data suggest Panx1 in SMCs could regulate the extent of sympathetic nerve constriction and blood pressure. The results also show the feasibility humanized Panx1-mouse models to test pharmacological candidates.

physiology↗

bioRxiv2022

miR167-ARF8, an auxin-responsive module involved in the formation of root-knot nematode-induced galls in tomato

O_LIRoot-knot nematodes (RKN) from genus Meloidogyne induce the dedifferentiation of root vascular cells into giant multinucleate feeding cells. These feeding cells result from an extensive reprogramming of gene expression in targeted root cells, as shown by transcriptomic analyses of galls or giant cells from various plant species. C_LIO_LISmall non-coding RNAs, and messenger RNAs from tomato (Solanum lycopersicum) galls and uninfected roots were sequenced. De novo microRNA prediction in the tomato genome identified microRNAs expressed in galls and uninfected roots. Statistical analyses identified 174 miRNA genes differentially expressed in galls at 7 and/or 14 days post infection (dpi). C_LIO_LIIntegrative analyses combining small non-coding RNA and transcriptome datasets with the specific sequencing of cleaved transcripts identified miRNA targets in tomato galls. Functional analyses of promoter-GUS fusions and CRISPR-Cas9 mutants highlighted the role of the miR167-regulated transcription factor AUXIN RESPONSE FACTOR 8 (ARF8) in giant cell formation. C_LI

plant biology↗

bioRxiv2021

An atypical class of non-coding small RNAs produced in rice leaves upon bacterial infection

Non-coding small RNAs (sRNA) act as mediators of gene silencing and regulate plant growth, development and stress responses. Early insights into plant sRNAs established a role in antiviral defense and they are now extensively studied across plant-microbe interactions. Here, sRNA sequencing discovered a class of sRNA in rice (Oryza sativa) specifically associated with foliar diseases caused by Xanthomonas oryzae bacteria. Xanthomonas-induced small RNAs (xisRNAs) loci were distinctively upregulated in response to diverse virulent strains at an early stage of infection producing a single duplex of 20-22nt sRNAs. xisRNAs production was dependent on the Type III secretion system, a major bacterial virulence factor for host colonization. xisRNA loci overlap with annotated transcripts sequences often encoding protein kinase domain proteins. A number of the corresponding rice cis-genes have documented functions in immune signaling and some xisRNA loci coincide with the coding sequence of a conserved kinase motif. xisRNAs exhibit features of small interfering RNAs and their biosynthesis depend on canonical components OsDCL1 and OsHEN1. xisRNA induction possibly mediates post-transcriptional gene silencing but they do not broadly suppress cis-genes expression on the basis of mRNA-seq data. Overall, our results identify a group of unusual sRNAs with a potential role in plant-microbe interactions.

molecular biology↗

bioRxiv2020

Learning a non-neutral conditioned stimulus: place preference in the crab Neohelice granulata

In the wild, being able to recognize and remember specific locations related to food sources and the associated attributes of landmarks is a cognitive trait important for survival. In the present work we show that the crab Neohelice granulata can be trained to associate a specific environment with an appetitive reward in a conditioned place preference task. After a single training trial, when the crabs were presented with a food pellet in the target quadrant of the training arena, they were able to form a long-term memory related to the event. This memory was evident at least 24 h after training and was protein-synthesis dependent. Importantly, the target area of the arena proved to be a non-neutral environment, given that animals initially avoided the target quadrant. In the present work we introduce for the first time an associative one-trial memory paradigm including a conditioned stimulus with a clear valence performed in a crustacean.

animal behavior and cognition↗