Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The entorhinal cortex modulates trace fear memory formation and neuroplasticity in the mouse lateral amygdala via cholecystokinin.

ABSTRACT: Although fear memory formation is essential for survival and fear-related mental disorders, the neural circuitry and mechanism are incompletely understood. Here, we utilized trace fear conditioning to study the formation of trace fear memory in mice. We identified the entorhinal cortex (EC) as a critical component of sensory signaling to the amygdala. We adopted both loss-of-function and gain-of-function experiments to demonstrate that release of the cholecystokinin (CCK) from the EC is required for trace fear memory formation. We discovered that CCK-positive neurons project from the EC to the lateral nuclei of the amygdala (LA), and inhibition of CCK-dependent signaling in the EC prevented long-term potentiation of the auditory response in the LA and formation of trace fear memory. In summary, high-frequency activation of EC neurons triggers the release of CCK in their projection terminals in the LA, potentiating auditory response in LA neurons. The neural plasticity in the LA leads to trace fear memory formation.

SUBMITTER: Feng H

PROVIDER: S-EPMC8629425 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Arc expression identifies the lateral amygdala fear memory trace.

Project description:Memories are encoded within sparsely distributed neuronal ensembles. However, the defining cellular properties of neurons within a memory trace remain incompletely understood. Using a fluorescence-based Arc reporter, we were able to visually identify the distinct subset of lateral amygdala (LA) neurons activated during auditory fear conditioning. We found that Arc-expressing neurons have enhanced intrinsic excitability and are preferentially recruited into newly encoded memory traces. Furthermore, synaptic potentiation of thalamic inputs to the LA during fear conditioning is learning-specific, postsynaptically mediated and highly localized to Arc-expressing neurons. Taken together, our findings validate the immediate-early gene Arc as a molecular marker for the LA neuronal ensemble recruited during fear learning. Moreover, these results establish a model of fear memory formation in which intrinsic excitability determines neuronal selection, whereas learning-related encoding is governed by synaptic plasticity.

| S-EPMC4759206 | biostudies-literature

Arc expression identifies the lateral amygdala fear memory trace.

Project description: Not available

| S-EPMC7609304 | biostudies-literature

Extinguishing trace fear engages the retrosplenial cortex rather than the amygdala.

Project description:Extinction learning underlies the treatment for a variety of anxiety disorders. Most of what is known about the neurobiology of extinction is based on standard "delay" fear conditioning, in which awareness is not required for learning. Little is known about how complex, explicit associations extinguish, however. "Trace" conditioning is considered to be a rodent model of explicit fear because it relies on both the cortex and hippocampus and requires explicit contingency awareness in humans. Here, we explore the neural circuit supporting trace fear extinction in order to better understand how complex memories extinguish. We first show that the amygdala is selectively involved in delay fear extinction; blocking intra-amygdala glutamate receptors disrupted delay, but not trace extinction. Further, ERK phosphorylation was increased in the amygdala after delay, but not trace extinction. We then identify the retrosplenial cortex (RSC) as a key structure supporting trace extinction. ERK phosphorylation was selectively increased in the RSC following trace extinction and blocking intra-RSC NMDA receptors impaired trace, but not delay extinction. These findings indicate that delay and trace extinction require different neural circuits; delay extinction requires plasticity in the amygdala whereas trace extinction requires the RSC. Anxiety disorders linked to explicit memory may therefore depend on cortical processes that have not been traditionally targeted by extinction studies based on delay fear.

| S-EPMC3959632 | biostudies-literature

Interference with reelin signaling in the lateral entorhinal cortex impairs spatial memory.

Project description:Entorhinal neurons receive extensive intracortical projections, and form the primary input to the hippocampus via the perforant pathway. The glutamatergic cells of origin for the perforant pathway are distinguished by their expression of reelin, a glycoprotein involved in learning and synaptic plasticity. The functional significance of reelin signaling within the entorhinal cortex, however, remains unexplored. To determine whether interrupting entorhinal reelin signaling might have consequences for learning and memory, we administered recombinant receptor-associated protein (RAP) into the lateral entorhinal cortex (LEC) of young Long-Evans rats. RAP prevents reelin from binding to its receptors, and we verified the knockdown of reelin signaling by quantifying the phosphorylation state of reelin's intracellular signaling target, disabled-1 (DAB1). Effective knockdown of reelin signaling was associated with impaired performance in the hippocampus-dependent version of the water maze. Moreover, inhibition of reelin signaling induced a localized loss of synaptic marker expression in the LEC. These observations support a role for entorhinal reelin signaling in spatial learning, and suggest that an intact reelin signaling pathway is essential for synaptic integrity in the adult entorhinal cortex.

| S-EPMC3148331 | biostudies-literature

Lateral entorhinal cortex lesions impair odor-context associative memory in male rats.

Project description:Lateral entorhinal cortex (LEC) has been hypothesized to process nonspatial, item information that is combined with spatial information from medial entorhinal cortex to form episodic memories within the hippocampus. Recent studies, however, have demonstrated that LEC has a role in integrating features of episodic memory prior to the hippocampus. While the precise role of LEC is still unclear, anatomical studies show that LEC is ideally placed to be a hub integrating multisensory information. The current study tests whether the role of LEC in integrating information extends to long-term multimodal item-context associations. In Experiment 1, male rats were trained on a context-dependent odor discrimination task, where two different contexts served as the cue to the correct odor. Rats were pretrained on the task and then received either bilateral excitotoxic LEC or sham lesions. Following surgery, rats were tested on the previously learned odor-context associations. Control rats showed good memory for the previously learned association but rats with LEC lesions showed significantly impaired performance relative to both their own presurgery performance and to control rats. Experiment 2 went on to test whether impairments in Experiment 1 were the result of LEC lesions impairing either odor or context memory retention alone. Male rats were trained on simple odor and context discrimination tasks that did not require integration of features to solve. Following surgery, both LEC and control rats showed good memory for previously learned odors and contexts. These data show that LEC is critical for long-term odor-context associative memory.

| S-EPMC9302644 | biostudies-literature

Optogenetic activation of presynaptic inputs in lateral amygdala forms associative fear memory.

Project description:In Pavlovian fear conditioning, the lateral amygdala (LA) has been highlighted as a key brain site for association between sensory cues and aversive stimuli. However, learning-related changes are also found in upstream sensory regions such as thalamus and cortex. To isolate the essential neural circuit components for fear memory association, we tested whether direct activation of presynaptic sensory inputs in LA, without the participation of upstream activity, is sufficient to form fear memory in mice. Photostimulation of axonal projections from the two main auditory brain regions, the medial geniculate nucleus of the thalamus and the secondary auditory cortex, was paired with aversive footshock. Twenty-four hours later the same photostimulation induced robust conditioned freezing and this fear memory formation was disrupted when glutamatergic synaptic transmission was locally blocked in the LA. Therefore, our results prove for the first time that synapses between sensory input areas and the LA, previously implicated as a crucial brain site for fear memory formation, actually are sufficient to serve as a conditioned stimulus. Our results strongly support the idea that the LA may be sufficient to encode and store associations between neutral cue and aversive stimuli during natural fear conditioning as a critical part of a broad fear memory engram.

| S-EPMC4201812 | biostudies-literature

Memory retrieval modulates spatial tuning of single neurons in the human entorhinal cortex.

Project description:The medial temporal lobe is critical for both spatial navigation and memory. Although single neurons in the medial temporal lobe activate to represent locations in the environment during navigation, how this spatial tuning relates to memory for events involving those locations remains unclear. We examined memory-related changes in spatial tuning by recording single-neuron activity from neurosurgical patients performing a virtual-reality object-location memory task. We identified 'memory-trace cells' with activity that was spatially tuned to the retrieved location of the specific object that participants were cued to remember. Memory-trace cells in the entorhinal cortex, in particular, encoded discriminable representations of different memories through a memory-specific rate code. These findings indicate that single neurons in the human entorhinal cortex change their spatial tuning to target relevant memories for retrieval.

| S-EPMC6897360 | biostudies-literature

Cholecystokinin from the entorhinal cortex enables neural plasticity in the auditory cortex.

Project description:Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.

| S-EPMC3945883 | biostudies-other

Comparative metabolic profiling of posterior parietal cortex, amygdala, and hippocampus in conditioned fear memory.

Project description:Fear conditioning and retrieval are suitable models to investigate the biological basis of various mental disorders. Hippocampus and amygdala neurons consolidate conditioned stimulus (CS)-dependent fear memory. Posterior parietal cortex is considered important for the CS-dependent conditioning and retrieval of fear memory. Metabolomic screening among functionally related brain areas provides molecular signatures and biomarkers to improve the treatment of psychopathologies. Herein, we analyzed and compared changes of metabolites in the hippocampus, amygdala, and posterior parietal cortex under the fear retrieval condition. Metabolite profiles of posterior parietal cortex and amygdala were similarly changed after fear memory retrieval. While the retrieval of fear memory perturbed various metabolic pathways, most metabolic pathways that overlapped among the three brain regions had high ranks in the enrichment analysis of posterior parietal cortex. In posterior parietal cortex, the most perturbed pathways were pantothenate and CoA biosynthesis, purine metabolism, glutathione metabolism, and NAD+ dependent signaling. Metabolites of posterior parietal cortex including 4'-phosphopantetheine, xanthine, glutathione, ADP-ribose, ADP-ribose 2'-phosphate, and cyclic ADP-ribose were significantly regulated in these metabolic pathways. These results point to the importance of metabolites of posterior parietal cortex in conditioned fear memory retrieval and may provide potential biomarker candidates for traumatic memory-related mental disorders.

| S-EPMC8493686 | biostudies-literature

Rapid amygdala responses during trace fear conditioning without awareness.

Project description:The role of consciousness in learning has been debated for nearly 50 years. Recent studies suggest that conscious awareness is needed to bridge the gap when learning about two events that are separated in time, as is true for trace fear conditioning. This has been repeatedly shown and seems to apply to other forms of classical conditioning as well. In contrast to these findings, we show that individuals can learn to associate a face with the later occurrence of a shock, even if they are unable to perceive the face. We used a novel application of magnetoencephalography (MEG) to non-invasively record neural activity from the amygdala, which is known to be important for fear learning. We demonstrate rapid (? 170-200 ms) amygdala responses during the stimulus free period between the face and the shock. These results suggest that unperceived faces can serve as signals for impending threat, and that rapid, automatic activation of the amygdala contributes to this process. In addition, we describe a methodology that can be applied in the future to study neural activity with MEG in other subcortical structures.

| S-EPMC4019542 | 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