Examination of CA1 hippocampal DNA methylation as a mechanism for closing of estrogen’s critical window
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ORGANISM(S): Rattus norvegicus
PROVIDER: GSE167038 | GEO | 2021/08/24
REPOSITORIES: GEO
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Project description:Examination of CA1 hippocampal DNA methylation as a mechanism for closing of estrogen’s critical window
| PRJNA702773 | ENA
Project description:There is a critical window for estrogen replacement therapy, beyond which estradiol (E2) fails to enhance cognition and N-methyl-D-aspartate (NMDA) receptor function, and E2-responsive transcription decreases. Much less attention has been given to the mechanism for closing of the critical window, which is thought to involve the decline in estrogen signaling cascades, possibly involving epigenetic mechanisms, including DNA methylation. This study investigated changes in DNA methylation in region CA1 of the hippocampus of ovariectomized female rats over the course of brain aging and in response to E2-treatment, using whole genome bisulfite sequencing. Differential methylation of CpG and non-CpG (CHG and CHH) sites and associated genes were characterized in aged controls (AC), middle-age controls (MC), and young controls (YC) and differential methylation in response to E2-treatment (T) was examined in each age group (AT-AC, MT-MC, and YT-YC). Possible candidate genes for the closing of the critical window were defined as those that were hypomethylated by E2-treatment in younger animals, but were unresponsive in aged animals. Gene ontology categories for possible critical window genes were linked to response to hormones (Adcyap1, Agtr2, Apob, Ahr, Andpro, Calm2, Cyp4a2, Htr1b, Nr3c2, Pitx2, Pth, Pdk4, Slc2a2, Tnc, and Wnt5a), including G-protein receptor signaling (Gpr22 and Rgs4). Other possible critical window genes were linked to glutamate synapses (Nedd4, Grm1, Grm7, and Grin3a). These results suggest that decreased E2 signaling with advanced age, and/or prolonged E2 deprivation, results in methylation of E2-responsive genes, including those involved in rapid E2 signaling, which may limit subsequent transcription.
| S-EPMC8371553 | biostudies-literature
Project description:The published finished human genome contained 340 gaps including 250 gaps in the euchromatic region. The reasons for these gaps were not fully understood, although subsequent analysis revealed that presence of segmentally duplicated sequences were a good predictor for the presence of gaps. However, not all segmentally duplicated regions contained gaps. We made a systemic effort to close euchromatic gaps and understand the nature of gap closing sequences. Our studies clearly demonstrate that the gap closing sequences analyzed were over 2.3-fold more enriched in segmental duplications and that about 40% of the gap closing sequences were structurally variant. The structural variant nature of gap closing sequences was verified by aCGH analysis, and by paired-end-sequence and fingerprint analysis of gap spanning clones from recently available human genome fosmid libraries from eight individuals. Identification and characterization of gap closing sequences provides an effective approach for closing the remaining euchromatic gaps in the human genome. Keywords: comparative genomic hybridization
2007-12-23 | GSE9075 | GEO
Project description:Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep. Neurons active during behavior reactivate in both structures during sleep, in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation. In the hippocampus, replay occurs within sharp wave-ripples: short bouts of high-frequency activity in area CA1 caused by excitatory activation from area CA3. In this work, we develop a computational model of ripple generation, motivated by in vivo rat data showing that ripples have a broad frequency distribution, exponential inter-arrival times and yet highly non-variable durations. Our study predicts that ripples are not persistent oscillations but result from a transient network behavior, induced by input from CA3, in which the high frequency synchronous firing of perisomatic interneurons does not depend on the time scale of synaptic inhibition. We found that noise-induced loss of synchrony among CA1 interneurons dynamically constrains individual ripple duration. Our study proposes a novel mechanism of hippocampal ripple generation consistent with a broad range of experimental data, and highlights the role of noise in regulating the duration of input-driven oscillatory spiking in an inhibitory network.
| S-EPMC4836732 | biostudies-literature
Project description:How does the information of spatiotemporal sequence stemming from the hippocampal CA3 area affect the postsynaptic membrane potentials of the hippocampal CA1 neurons? In a recent study, we observed hierarchical clusters of the distribution of membrane potentials of CA1 neurons, arranged according to the history of input sequences (Fukushima et al Cogn Neurodyn 1(4):305-316, 2007). In the present paper, we deal with the dynamical mechanism generating such a hierarchical distribution. The recording data were investigated using return map analysis. We also deal with a collective behavior at population level, using a reconstructed multi-cell recording data set. At both individual cell and population levels, a return map of the response sequence of CA1 pyramidal cells was well approximated by a set of contractive affine transformations, where the transformations represent self-organized rules by which the input pattern sequences are encoded. These findings provide direct evidence that the information of temporal sequences generated in CA3 can be self-similarly represented in the membrane potentials of CA1 pyramidal cells.
| S-EPMC2727166 | biostudies-other
Project description:Using Ca(2+) imaging in freely behaving mice that repeatedly explored a familiar environment, we tracked thousands of CA1 pyramidal cells' place fields over weeks. Place coding was dynamic, as each day the ensemble representation of this environment involved a unique subset of cells. However, cells in the ?15-25% overlap between any two of these subsets retained the same place fields, which sufficed to preserve an accurate spatial representation across weeks.
| S-EPMC3784308 | biostudies-literature
Project description:Hippocampal CA1 pyramidal neurons have frequently been regarded as a homogeneous cell population in biophysical, pharmacological and modeling studies. We found robust differences between pyramidal neurons residing in the deep and superficial CA1 sublayers in rats. Compared with their superficial peers, deep pyramidal cells fired at higher rates, burst more frequently, were more likely to have place fields and were more strongly modulated by slow oscillations of sleep. Both deep and superficial pyramidal cells fired preferentially at the trough of theta oscillations during maze exploration, whereas deep pyramidal cells shifted their preferred phase of firing to the peak of theta during rapid eye movement (REM) sleep. Furthermore, although the majority of REM theta phase-shifting cells fired at the ascending phase of gamma oscillations during waking, nonshifting cells preferred the trough. Thus, CA1 pyramidal cells in adjacent sublayers can address their targets jointly or differentially, depending on brain states.
| S-EPMC3164922 | biostudies-literature
Project description:Sequential neural dynamics encoded by "time cells" play a crucial role in hippocampal function. However, the role of hippocampal sequential neural dynamics in associative learning is an open question. In this manuscript, we used two-photon Ca2+ imaging of dorsal CA1 pyramidal neurons in head-fixed mice performing a go-no-go associative learning task. We found that pyramidal cells responded differentially to the rewarded or unrewarded stimuli. The stimuli were decoded accurately from the activity of the neuronal ensemble, and accuracy increased substantially as the animal learned to differentiate the stimuli. Decoding the stimulus from individual pyramidal cells that responded differentially revealed that decision-making took place at discrete times after stimulus presentation. Lick prediction decoded from the ensemble activity of cells in dCA1 correlated linearly with lick behavior indicating that sequential activity of pyramidal cells in dCA1 constitutes a temporal memory map used for decision-making in associative learning.
| S-EPMC10592611 | biostudies-literature
Project description:Whether an individual synapse releases single or multiple vesicles of transmitter per action potential is contentious and probably depends on the type of synapse. One possibility is that multivesicular release (MVR) is determined by the instantaneous release probability (Pr) and therefore can be controlled by activity-dependent changes in Pr. We investigated transmitter release across a range of Pr at synapses between Schaffer collaterals (SCs) and CA1 pyramidal cells in acute hippocampal slices using patch-clamp recordings. The size of the synaptic glutamate transient was estimated by the degree of inhibition of AMPA receptor EPSCs with the rapidly equilibrating antagonist gamma-D-glutamylglycine. The glutamate transient sensed by AMPA receptors depended on Pr but not spillover, indicating that multiple vesicles are essentially simultaneously released from the same presynaptic active zone. Consistent with an enhanced glutamate transient, increasing Pr prolonged NMDA receptor EPSCs when glutamate transporters were inhibited. We suggest that MVR occurs at SC-CA1 synapses when Pr is elevated by facilitation and that MVR may be a phenomenon common to many synapses throughout the CNS.
| S-EPMC2670931 | biostudies-literature
Project description:BackgroundSmaller hippocampal volume in patients with posttraumatic stress disorder (PTSD) represents the most consistently reported structural alteration in the brain. Subfields of the hippocampus play distinct roles in encoding and processing of memories, which are disrupted in PTSD. We examined PTSD-associated alterations in 12 hippocampal subfields in relation to global hippocampal shape, and clinical features.MethodsCase-control cross-sectional studies of U.S. military veterans (n = 282) from the Iraq and Afghanistan era were grouped into PTSD (n = 142) and trauma-exposed controls (n = 140). Participants underwent clinical evaluation for PTSD and associated clinical parameters followed by MRI at 3 T. Segmentation with FreeSurfer v6.0 produced hippocampal subfield volumes for the left and right CA1, CA3, CA4, DG, fimbria, fissure, hippocampus-amygdala transition area, molecular layer, parasubiculum, presubiculum, subiculum, and tail, as well as hippocampal meshes. Covariates included age, gender, trauma exposure, alcohol use, depressive symptoms, antidepressant medication use, total hippocampal volume, and MRI scanner model.ResultsSignificantly lower subfield volumes were associated with PTSD in left CA1 (P = 0.01; d = 0.21; uncorrected), CA3 (P = 0.04; d = 0.08; uncorrected), and right CA3 (P = 0.02; d = 0.07; uncorrected) only if ipsilateral whole hippocampal volume was included as a covariate. A trend level association of L-CA1 with PTSD (F4, 221 = 3.32, P = 0.07) is present and the other subfield findings are nonsignificant if ipsilateral whole hippocampal volume is not included as a covariate. PTSD-associated differences in global hippocampal shape were nonsignificant.ConclusionsThe present finding of smaller hippocampal CA1 in PTSD is consistent with model systems in rodents that exhibit increased anxiety-like behavior from repeated exposure to acute stress. Behavioral correlations with hippocampal subfield volume differences in PTSD will elucidate their relevance to PTSD, particularly behaviors of associative fear learning, extinction training, and formation of false memories.
| S-EPMC6261348 | biostudies-literature