Project description:Zinc is an essential trace element that is closely related to learning and memory ability. The hippocampus plays an important role in learning and memory and has the highest zinc concentration in the brain. Severe zinc deficiency (zinc-deprived diet) significantly alter hippocampal protein expression and impair learning and memory abilities. However, no study has investigated the effects of marginal zinc deficiency (low zinc diet) on hippocampal proteins and learning and memory abilities. In this study, the rat model after 4 and 8 weeks of feeding with low zinc diet was first used to identify and quantify the hippocampal proteins of low zinc rats by high-thoughput proteomics technology. Explore the changes of hippocampus proteome patterns after 4 and 8 weeks of feeding with low zinc diet were compared with those in control rats.
Project description:Specific genes or encoded proteins are involved in regulating various learning models of different species through certain signaling pathways,but whether there are also regulatory genes during bimodal learning and memory is largely unknown. Using a multi-omics approach to examine gene expression changes in bees brain performed with three different learning assays, a general up-regulation of genes and proteins were observed in bimodal learning compared to controls. Protein-protein network predictions of differential proteins together with FISH assays suggest ALDH7A1 may be involved in regulation of bimodal learning and memory. Injecting siRNA-ALDH7A1 to the bee brain results in significant inhibition the expressions of ALDH7A1 and regucalcin, and increase β-alanine content. Interestingly, we found that loss of ALDH7A1 only affect visual-olfactory bimodal learning and memory, but not single visual or olfactory conditioned learning after ALDH7A1-RNAi in bees. Therefore, our data suggests that ALDH7A1 may affect bimodal learning and memory though controlling β-alanine related plasticity mechanisms.
Project description:The ability to form memories is a prerequisite for an organismâs behavioural adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell-types, and three time-points before and after contextual learning. Here we show that histone modifications predominantly change during memory acquisition and correlate surprisingly little with changes in gene expression. While long-lasting changes are almost exclusive to neurons, learning-related histone modification and DNA methylation changes occur also in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provides evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring. We examined chromatin modification changes in two distinct mouse brain regions (CA1 and ACC), two cell-types (neurons, non-neurons), and three time-points before and after contextual learning (naive, 1h, 4w).
Project description:We inhibited RNA polymerase I by genetic ablation of the basal transcription factor TIF-IA in adult hippocampal neurons. Nucleolar stress resulted in progressive neurodegeneration, although with a differential vulnerability within the CA1, CA3 and dentate gyrus. Here, we investigate the consequences of nucleolar stress on learning and memory. The mutant mice do not show any impairment in the behavioral memory tests, suggesting the activation of adaptive mechanisms. In fact, we observe a significantly enhanced learning and re-learning corresponding to the initial inhibition of rRNA transcription and accompanied by aberrant synaptic plasticity. To explore the putative molecular mechanisms underlying these adaptative changes we profiled global gene expression of control and TIFIACaMKCreERT2 mutant mice (5-6 mice/genotype) 4 weeks after induction of the mutation (injection of tamoxifen).
Project description:A comprehensive landscape of epigenomic events regulated by the Reelin signaling through activation of specific cohort of cis-regulatory enhancer elements (LRN-enhancers), which involves the proteolytical processing of the LRP8 receptor by the gamma-secretase activity and is required for learning and memory behavior All ChIP-Seq experiments were designed to understand the unique signature and function of LRN-enhancers in signaling pathways of learning and memory.
Project description:A theoretical framework for the function of the medial temporal lobe system in memory defines differential contributions of the hippocampal subregions with regard to pattern recognition retrieval processes and encoding of new information. To investigate molecular programs of relevance, we designed a spatial learning protocol to engage a pattern separation function to encode new information. After background training, two groups of animals experienced the same new training in a novel environment, however only one group was provided spatial information and demonstrated spatial memory in a retention test. Global transcriptional analysis of the microdissected subregions of the hippocampus exposed a CA3 pattern that was sufficient to clearly segregate spatial learning animals from control. Individual gene and functional group analysis anchored these results to previous work in neural plasticity. From a multitude of expression changes, increases in camk2a, rasgrp1 and nlgn1 were confirmed by in situ hybridization. Furthermore, siRNA inhibition of nlgn1 within the CA3 subregion impaired spatial memory performance, pointing to mechanisms of synaptic remodeling as a basis for rapid encoding of new information in long-term memory. Experiment Overall Design: RNA samples from animals subjected to a spatial learning paradigm were compared to controls using Affymetirx RAE230a chips. An N of 7 was used in each of the two experimental conditions.
Project description:A theoretical framework for the function of the medial temporal lobe system in memory defines differential contributions of the hippocampal subregions with regard to pattern recognition retrieval processes and encoding of new information. To investigate molecular programs of relevance, we designed a spatial learning protocol to engage a pattern separation function to encode new information. After background training, two groups of animals experienced the same new training in a novel environment, however only one group was provided spatial information and demonstrated spatial memory in a retention test. Global transcriptional analysis of the microdissected subregions of the hippocampus exposed a CA3 pattern that was sufficient to clearly segregate spatial learning animals from control. Individual gene and functional group analysis anchored these results to previous work in neural plasticity. From a multitude of expression changes, increases in camk2a, rasgrp1 and nlgn1 were confirmed by in situ hybridization. Furthermore, siRNA inhibition of nlgn1 within the CA3 subregion impaired spatial memory performance, pointing to mechanisms of synaptic remodeling as a basis for rapid encoding of new information in long-term memory. Experiment Overall Design: RNA samples from animals subjected to a spatial learning paradigm were compared to controls using Affymetirx RAE230a chips. An N of 6 was used in each of the two experimental conditions.
Project description:A theoretical framework for the function of the medial temporal lobe system in memory defines differential contributions of the hippocampal subregions with regard to pattern recognition retrieval processes and encoding of new information. To investigate molecular programs of relevance, we designed a spatial learning protocol to engage a pattern separation function to encode new information. After background training, two groups of animals experienced the same new training in a novel environment, however only one group was provided spatial information and demonstrated spatial memory in a retention test. Global transcriptional analysis of the microdissected subregions of the hippocampus exposed a CA3 pattern that was sufficient to clearly segregate spatial learning animals from control. Individual gene and functional group analysis anchored these results to previous work in neural plasticity. From a multitude of expression changes, increases in camk2a, rasgrp1 and nlgn1 were confirmed by in situ hybridization. Furthermore, siRNA inhibition of nlgn1 within the CA3 subregion impaired spatial memory performance, pointing to mechanisms of synaptic remodeling as a basis for rapid encoding of new information in long-term memory. Experiment Overall Design: RNA samples from animals subjected to a spatial learning paradigm were compared to controls using Affymetirx RAE230a chips. An N of 7 was used in each of the two experimental conditions.
Project description:The mechanisms underlying age-associated memory impairment are not well understood. We have shown that the onset of memory disturbances in the aging brain is associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation. To analyze if deregulated H4K12 acetylation impacts on learning-induced gene-expression required for memory consolidation we performed a high-density oligonucleotide microarray to compare the entire hippocampal gene-expression profile of 3 and 16-month-old mice during memory consolidation.