19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Encoding of contextual fear memory in hippocampal–amygdala circuit

      research-article
      ,
      Nature Communications
      Nature Publishing Group UK
      Learning and memory, Neural circuits, Synaptic plasticity

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Abstract

          Previous studies implicate the hippocampal–amygdala pathway in contextual fear conditioning, in which animals learn to associate a neutral context with an aversive stimulus and display fear responses to dangerous situations. Here the authors show that selective strengthening of hippocampal–amygdala pathway contributes to encoding adaptive fear memory for threat-predictive context.

          Related collections

          Most cited references40

          • Record: found
          • Abstract: found
          • Article: not found

          Short-term synaptic plasticity.

          Synaptic transmission is a dynamic process. Postsynaptic responses wax and wane as presynaptic activity evolves. This prominent characteristic of chemical synaptic transmission is a crucial determinant of the response properties of synapses and, in turn, of the stimulus properties selected by neural networks and of the patterns of activity generated by those networks. This review focuses on synaptic changes that result from prior activity in the synapse under study, and is restricted to short-term effects that last for at most a few minutes. Forms of synaptic enhancement, such as facilitation, augmentation, and post-tetanic potentiation, are usually attributed to effects of a residual elevation in presynaptic [Ca(2+)]i, acting on one or more molecular targets that appear to be distinct from the secretory trigger responsible for fast exocytosis and phasic release of transmitter to single action potentials. We discuss the evidence for this hypothesis, and the origins of the different kinetic phases of synaptic enhancement, as well as the interpretation of statistical changes in transmitter release and roles played by other factors such as alterations in presynaptic Ca(2+) influx or postsynaptic levels of [Ca(2+)]i. Synaptic depression dominates enhancement at many synapses. Depression is usually attributed to depletion of some pool of readily releasable vesicles, and various forms of the depletion model are discussed. Depression can also arise from feedback activation of presynaptic receptors and from postsynaptic processes such as receptor desensitization. In addition, glial-neuronal interactions can contribute to short-term synaptic plasticity. Finally, we summarize the recent literature on putative molecular players in synaptic plasticity and the effects of genetic manipulations and other modulatory influences.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Optogenetic stimulation of a hippocampal engram activates fear memory recall

            A specific memory is thought to be encoded by a sparse population of neurons 1,2 . These neurons can be tagged during learning for subsequent identification 3 and manipulation 4,5,6 . Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, a critical question of sufficiency remains: can one elicit the behavioral output of a specific memory by directly activating a population of neurons that was active during learning? Here we show that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behavior. We labeled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) 7,8 and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear conditioned mice with cells labeled by EYFP instead of ChR2. Finally, activation of cells labeled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context-specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A shared neural ensemble links distinct contextual memories encoded close in time

              Recent studies suggest the hypothesis that a shared neural ensemble may link distinct memories encoded close in time 1–13 . According to the memory allocation hypothesis 1,2 , learning triggers a temporary increase in neuronal excitability 14–16 that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Accordingly, we report that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Multiple convergent findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability 16,17 , do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged animals, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by aging could affect the temporal structure of memories, thus impairing efficient recall of related information.
                Bookmark

                Author and article information

                Contributors
                juncho@ucr.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                13 March 2020
                13 March 2020
                2020
                : 11
                : 1382
                Affiliations
                ISNI 0000 0001 2222 1582, GRID grid.266097.c, Department of Molecular, Cell and Systems Biology, , University of California, ; Riverside, CA 92521 USA
                Author information
                http://orcid.org/0000-0002-6844-3583
                Article
                15121
                10.1038/s41467-020-15121-2
                7069961
                32170133
                378bf2a1-b0ed-4dda-95ae-a4b2bba9bbfd
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 December 2018
                : 15 February 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000025, U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH);
                Award ID: R01MH118339
                Award ID: R56MH113894
                Award Recipient :
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
                Funded by: FundRef https://doi.org/10.13039/100009035, UC | UC Riverside | Academic Senate, University of California, Riverside (Academic Senate, UCR);
                Award ID: Initial Complement Funds
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                learning and memory,neural circuits,synaptic plasticity
                Uncategorized
                learning and memory, neural circuits, synaptic plasticity

                Comments

                Comment on this article