Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats.

ABSTRACT: Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT4) administration increased the level of free triiodothyronine (FT3) and free tetraiodothyroxine (FT4) not only in serum but also in hippocampus. In addition, a single systemic LT4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT4 (0.4 μg/μl, 1 μl/side) was injected bilaterally into hippocampus. Rats given LT4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT4 did not affect rats' locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders.

SUBMITTER: Yu D

PROVIDER: S-EPMC5534464 | biostudies-other | 2017

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Chemogenetic inactivation of ventral hippocampal glutamatergic neurons disrupts consolidation of contextual fear memory.

Project description:Synaptic consolidation is a process thought to consolidate memory in the brain. Although lesion studies have mainly implicated the hippocampus (HPC) in this process, it is unknown which cell type(s) or regions of the HPC might be essential for synaptic consolidation. To selectively and reversibly suppress hippocampal neuronal activity during this process, we developed a new Gi-DREADD (hM4Di) transgenic mouse for in vivo manipulation of neuronal activity in freely moving animals. We found that CA1 pyramidal neurons could be dose-dependently inactivated by clozapine-n-oxide (CNO). Inactivation of hippocampal neurons within 6 h immediately after conditioned fear training successfully impaired the consolidation of contextual memory, without disturbing cued memory. To anatomically define the brain subregion critical for the behavioral effects, hM4Di viral vectors were transduced and selectively expressed in the glutamatergic neurons in either the dorsal or ventral HPC. Significantly, we found that selective inactivation of ventral but not dorsal glutamatergic hippocampal neurons suppressed the synaptic consolidation of contextual memory.

| S-EPMC4059896 | biostudies-other

Hippocampal Wnt3a is Necessary and Sufficient for Contextual Fear Memory Acquisition and Consolidation.

Project description:The Wnt signaling pathway plays critical roles in development. However, to date, the role of Wnts in learning and memory in adults is still not well understood. Here, we aimed to investigate the roles and mechanisms of Wnts in hippocampal-dependent contextual fear conditioning (CFC) memory formation in adult mice. CFC training induced the secretion and expression of Wnt3a and the activation of its downstream Wnt/Ca(2+) and Wnt/β-catenin signaling pathways in the dorsal hippocampus (DH). Intrahippocampal infusion of Wnt3a antibody impaired CFC acquisition and consolidation, but not expression. Using the Wnt antagonist sFRP1 or the canonical Wnt inhibitor Dkk1, we found that Wnt/Ca(2+) and Wnt/β-catenin signaling pathways were involved in acquisition and consolidation, respectively. Moreover, we found Wnt3a signaling is not only necessary but also sufficient for CFC memory. Intrahippocampal infusion of exogenous Wnt3a could enhance acquisition and consolidation of CFC. Overexpression of constitutively active β-catenin in the DH could rescue the deficit in CFC memory consolidation, but not acquisition induced by Wnt3a antibody injection, which suggests β-catenin signaling pathway acts downstream of Wnt3a to mediate CFC memory consolidation. Our study may help further the understanding of the precise regulation of Wnt3a in differential memory phases depending on divergent signaling pathways.

| S-EPMC4626827 | biostudies-literature

Gene expression in rat hippocampal CA1 during the consolidation of contextual fear memory

Project description:Adult rats (male Lister hooded) received a single unsignaled scrambled footshock (0.5 mA for 2 s) 2 min into a 3min exposure to a novel context. One half rats received bilateral microinfusions (1 microlitre/hemisphere) of 2 nmol/microlitre BDNF antisense ODN (BDNFASO, 5’-TCTTCCCCTTTTAATGGT-3’ in PBS, pH 7.4) or BDNF missense ODN (BDNFMSO, 5’ -ATACTTTCTGTTCTTGCC-3’ in PBS, pH 7.4) into the dorsal hippocampus (AP -3.50, relative to bregma), 90 min before contextual fear conditioning (CFC). Infusions were made in awake rats via previously surgically implanted indwelling stainless steel cannula. Rats were housed in the home cages at all times outside the conditioning procedure. Rats were killed by CO2 inhalation 2 hours after CFC. CA1 enriched dorsal hippocampus was immediately dissected on ice before rapid freezing and storage at -80oC. The BDNFASO-infused group represent consolidation-impaired rats.

2015-09-25 | GSE66150 | GEO

Prior episode of colitis impairs contextual fear memory.

Project description:Accumulating evidence has shown that intestinal inflammations in inflammatory bowel disease (IBD) also drive pathological responses in organs outside the intestine, including the brain. Previous studies using the dextran sodium sulfate (DSS)-induced colitis model have shown that colonic inflammation contributes to the development of anxiety- and depression-related behaviors; however, little is known about whether memory function is affected. Here, we subjected male and female C57BL/6J mice to DSS-induced colitis for 6 days, followed by Pavlovian conditioned fear (CF) tests 15 days after the start of inflammation, when local colonic inflammation has receded. The contextual and cued CF tests were used to assess associative fear memory. We found that DSS-induced colitis led to significant impairment in contextual fear memory in both male and female mice; on the other hand, auditory cued fear memories were comparable between control and DSS-treated mice. There were marked signs of astrogliosis in the hippocampal regions 17 days (D17) after colitis induction. Furthermore, molecular characterization of hippocampi showed marked but transient increases in the expression of inflammatory genes Nfkb, Trem2 (microglial marker), GFAP (astrocyte marker), Il1b, and S100a8 in DSS-treated mice. While the expression of Nfkb, Trem2, and GFAP showed a peak on day 10, the S100a8 expression was high on days 10 and 17 and subsided on day 42. Interestingly, expression of Bdnf remained elevated in the times assessed (D10, 17, 42). Together, these results demonstrated that DSS-induced colitis could induce prolonged neuroinflammation and impaired contextual fear memory.

| S-EPMC9426209 | biostudies-literature

Overexpression of SIRT6 in the hippocampal CA1 impairs the formation of long-term contextual fear memory.

Project description:Histone modifications have been implicated in learning and memory. Our previous transcriptome data showed that expression of sirtuins 6 (SIRT6), a member of Histone deacetylases (HDACs) family in the hippocampal cornu ammonis 1 (CA1) was decreased after contextual fear conditioning. However, the role of SIRT6 in the formation of memory is still elusive. In the present study, we found that contextual fear conditioning inhibited translational expression of SIRT6 in the CA1. Microinfusion of lentiviral vector-expressing SIRT6 into theCA1 region selectively enhanced the expression of SIRT6 and impaired the formation of long-term contextual fear memory without affecting short-term fear memory. The overexpression of SIRT6 in the CA1 had no effect on anxiety-like behaviors or locomotor activity. Also, we also found that SIRT6 overexpression significantly inhibited the expression of insulin-like factor 2 (IGF2) and amounts of proteins and/or phosphoproteins (e.g. Akt, pAkt, mTOR and p-mTOR) related to the IGF2 signal pathway in the CA1. These results demonstrate that the overexpression of SIRT6 in the CA1 impaired the formation of long-term fear memory, and SIRT6 in the CA1 may negatively modulate the formation of contextual fear memory via inhibiting the IGF signaling pathway.

| S-EPMC4702175 | biostudies-literature

Time of Day-Dependent Alteration of Hippocampal Rac1 Activation Regulates Contextual Fear Memory in Rats.

Project description:Fear memory in species varies according to the time of the day. Although the underlying molecular mechanisms have been extensively explored, they remain largely unknown. Here, we report that hippocampal Rac1 activity undergoes a time of day-dependent alteration both in nocturnal rats and diurnal tree shrews and that training at the lower hippocampal Rac1 activation period during the night leads to better contextual fear memory in rats. Furthermore, day and night reversion by 24 h darkness/24 h light housing inverses the external clock time of hippocampal Rac1 activation, but the better contextual fear memory still coincides with the lower Rac1 activation in rats during the night. Interestingly, exogenous melatonin treatment promotes hippocampal Rac1 activity and impairs better contextual fear memory acquired at the lower Rac1 activation period during the night, and Rac1-specific inhibitor NSC23766 compromises the effect of melatonin. These results suggest that the time of day-dependent alteration of hippocampal Rac1 activation regulates contextual fear memory in rats by forgetting.

| S-EPMC9245039 | biostudies-literature

Encoding of contextual fear memory in hippocampal-amygdala circuit.

Project description:In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal-amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1-BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1-BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.

| S-EPMC7069961 | biostudies-literature

TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.

Project description:Memory formation requires de novo protein synthesis, and memory disorders may result from misregulated synthesis of critical proteins that remain largely unidentified. Plasma membrane ion channels and receptors are likely candidates given their role in regulating neuron excitability, a candidate memory mechanism. Here we conduct targeted molecular monitoring and quantitation of hippocampal plasma membrane proteins from mice with intact or impaired contextual fear memory to identify putative candidates. Here we report contextual fear memory deficits correspond to increased Trpc3 gene and protein expression, and demonstrate TRPC3 regulates hippocampal neuron excitability associated with memory function. These data provide a mechanistic explanation for enhanced contextual fear memory reported herein following knockdown of TRPC3 in hippocampus. Collectively, TRPC3 modulates memory and may be a feasible target to enhance memory and treat memory disorders.

| S-EPMC4677051 | biostudies-literature

Allosteric nanobodies uncover a role of hippocampal mGlu2 receptor homodimers in contextual fear consolidation.

Project description:Antibodies have enormous therapeutic and biotechnology potential. G protein-coupled receptors (GPCRs), the main targets in drug development, are of major interest in antibody development programs. Metabotropic glutamate receptors are dimeric GPCRs that can control synaptic activity in a multitude of ways. Here we identify llama nanobodies that specifically recognize mGlu2 receptors, among the eight subtypes of mGluR subunits. Among these nanobodies, DN10 and 13 are positive allosteric modulators (PAM) on homodimeric mGlu2, while DN10 displays also a significant partial agonist activity. DN10 and DN13 have no effect on mGlu2-3 and mGlu2-4 heterodimers. These PAMs enhance the inhibitory action of the orthosteric mGlu2/mGlu3 agonist, DCG-IV, at mossy fiber terminals in the CA3 region of hippocampal slices. DN13 also impairs contextual fear memory when injected in the CA3 region of hippocampal region. These data highlight the potential of developing antibodies with allosteric actions on GPCRs to better define their roles in vivo.

| S-EPMC5719040 | biostudies-literature

The effect of ketamine on the consolidation and extinction of contextual fear memory.

Project description:Ketamine, principally an antagonist of N-methyl-?-aspartate receptors, induces schizophrenia-like symptoms in adult humans, warranting its use in the investigation of psychosis-related phenotypes in animal models. Genomic studies further implicate N-methyl-?-aspartate receptor-mediated processes in schizophrenia pathology, together with more broadly-defined synaptic plasticity and associative learning processes. Strong pathophysiological links have been demonstrated between fear learning and psychiatric disorders such as schizophrenia. To further investigate the impact of ketamine on associative fear learning, we studied the effects of pre- and post-training ketamine on the consolidation and extinction of contextual fear memory in rats. Administration of 25 mg/kg ketamine prior to fear conditioning did not affect consolidation when potentially confounding effects of state dependency were controlled for. Pre-training ketamine (25 mg/kg) impaired the extinction of the conditioned fear response, which was mirrored with the use of a lower dose (8 mg/kg). Post-training ketamine (25 mg/kg) had no effect on the consolidation or extinction of conditioned fear. These observations implicate processes relating to the extinction of contextual fear memory in the manifestation of ketamine-induced phenotypes, and are consistent with existing hypotheses surrounding abnormal associative learning in schizophrenia.

| S-EPMC5818023 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data