16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Chasing the addicted engram: identifying functional alterations in Fos-expressing neuronal ensembles that mediate drug-related learned behavior

      research-article
      1 , 2
      Learning & Memory
      Cold Spring Harbor Laboratory Press

      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

          Given that addiction has been characterized as a disorder of maladaptive learning and memory, one critical question is whether there are unique physical adaptations within neuronal ensembles that support addiction-related learned behavior. The search for the physical mechanisms of encoding these and other memories in the brain, often called the engram as a whole, continues despite decades of research. As we develop new technologies and tools that allow us to study cue- and behavior-activated Fos-expressing neuronal ensembles, the possibility of identifying the engrams of learning and memory is moving into the realm of reality rather than speculation. It has become clear from recent studies that there are specific functional, electrophysiological alterations unique to Fos-expressing ensemble neurons that may participate in encoding memories. The ultimate goal is to identify the addicted engram and reverse the physical changes that support this maladaptive form of learning.

          Related collections

          Most cited references98

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

          A synaptic model of memory: long-term potentiation in the hippocampus.

          Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The neural basis of drug craving: an incentive-sensitization theory of addiction.

            This paper presents a biopsychological theory of drug addiction, the 'Incentive-Sensitization Theory'. The theory addresses three fundamental questions. The first is: why do addicts crave drugs? That is, what is the psychological and neurobiological basis of drug craving? The second is: why does drug craving persist even after long periods of abstinence? The third is whether 'wanting' drugs (drug craving) is attributable to 'liking' drugs (to the subjective pleasurable effects of drugs)? The theory posits the following. (1) Addictive drugs share the ability to enhance mesotelencephalic dopamine neurotransmission. (2) One psychological function of this neural system is to attribute 'incentive salience' to the perception and mental representation of events associated with activation of the system. Incentive salience is a psychological process that transforms the perception of stimuli, imbuing them with salience, making them attractive, 'wanted', incentive stimuli. (3) In some individuals the repeated use of addictive drugs produces incremental neuroadaptations in this neural system, rendering it increasingly and perhaps permanently, hypersensitive ('sensitized') to drugs and drug-associated stimuli. The sensitization of dopamine systems is gated by associative learning, which causes excessive incentive salience to be attributed to the act of drug taking and to stimuli associated with drug taking. It is specifically the sensitization of incentive salience, therefore, that transforms ordinary 'wanting' into excessive drug craving. (4) It is further proposed that sensitization of the neural systems responsible for incentive salience ('for wanting') can occur independently of changes in neural systems that mediate the subjective pleasurable effects of drugs (drug 'liking') and of neural systems that mediate withdrawal. Thus, sensitization of incentive salience can produce addictive behavior (compulsive drug seeking and drug taking) even if the expectation of drug pleasure or the aversive properties of withdrawal are diminished and even in the face of strong disincentives, including the loss of reputation, job, home and family. We review evidence for this view of addiction and discuss its implications for understanding the psychology and neurobiology of addiction.
              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

                Author and article information

                Journal
                Learn Mem
                Learn. Mem
                learnmem
                Learning & Memory
                Cold Spring Harbor Laboratory Press
                1072-0502
                1549-5485
                September 2018
                : 25
                : 9
                : 455-460
                Affiliations
                [1 ]Office of the Scientific Director; Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA
                [2 ]Neuronal Ensembles in Addiction Section; Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA
                Author notes
                Corresponding author: leslie.ramsey@ 123456nih.gov
                Author information
                http://orcid.org/0000-0001-5804-7061
                Article
                LM046698Whi
                10.1101/lm.046698.117
                6097770
                30115767
                6f49ae96-3bd9-41f0-a9e6-e0895507c0c4
                Published by Cold Spring Harbor Laboratory Press

                This is a work of the US Government.

                History
                : 12 June 2018
                : 9 July 2018
                Page count
                Pages: 6
                Funding
                Funded by: Intramural Research Program
                Funded by: National Institute on Drug Abuse , open-funder-registry 10.13039/100000026;
                Funded by: National Institutes of Health , open-funder-registry 10.13039/100000002;
                Categories
                Review

                Comments

                Comment on this article