The original concept of consolidation considers that memory requires time to be fixed. Since 2000, a comparable protein-dependent re-stabilization phase, called reconsolidation, has been assumed to ...take place after memory retrieval. This consolidation/reconsolidation hypothesis, has dominated the literature for more than 50 years, despite compelling evidence that is inconsistent with it. In this review, we present an historical overview and explain how, despite serious criticisms, this hypothesis has persisted for decades and become accepted as a dogma. Based on both older and more recent evidence, we next propose the concept of memory integration which involves the linkage or embedding of new material into an already existing representation. We believe integration provides a viable explanation for retrograde amnesia in place of the consolidation/reconsolidation hypothesis. Integration can further be the basis for several major cases of memory alteration such as time dependent memory enhancement, interference, counter-conditioning, updating and other instances of memory malleability. In a final section we consider the implications this new concept may have for memory processes and its translational applications.
Abstract Intrusive re-experiencing of a trauma is a core symptom in post-traumatic stress disorder (PTSD), and is often triggered by contextual cues associated with the event. It is not yet ...established if intrusive re-experiencing is the consequence of PTSD, or if it could contribute to the development of PTSD following a traumatic event. The present study (1) examined the impact of repeated brief re-exposures to trauma reminders on the strength of PTSD-like symptoms, as well as on their time-development and (2) investigated the reactivity over time to these cues in trauma resilient and vulnerable rats, defined on the basis of the PTSD-like symptoms they demonstrated. Rats were exposed to a Single Prolonged Stress, combining three different stresses (2-hrs restraint, 20-min forced swim and CO2 unconsciousness) delivered together with tone and odor cues and preceded by an inhibitory avoidance conditioning or a control procedure. During the following two weeks, reminded rats were briefly re-exposed to trauma-associated cues either 4 or 8 times. The results indicated that 4 re-exposures to the same cue strengthened PTSD-like symptoms (anxiety, arousal, fear to trauma-cue). However 8 re-exposures to similar or different trauma-cues did not alter PTSD-like symptoms and led to a rapid extinction of the fear reactivity to these cues. The present results further indicated that shortly after trauma, both resilient and vulnerable rats strongly reacted to trauma-associated cues, while only vulnerable rats reacted long after the trauma, suggesting a slower loss of fear responses to trauma cues in these rats. We concluded that re-experiencing may participate in, but cannot be solely responsible for, the development of long-term PTSD effects.
•Some traumatized rats develop PTSD symptoms while others are resilient.•These susceptible rats avoided trauma-related stimuli, as PTSD subjects.•A single amphetamine injection delivered in trauma ...context abolished PTSD symptoms.•Positive mood combined with trauma memory reactivation induce memory remodeling.
The present study had two main goals. First, to investigate whether an animal model of post traumatic stress disorder (PTSD), single prolonged stress (SPS) leads to one of the main PTSD symptom: avoidance of trauma-related stimuli. Second, to investigate whether a single amphetamine injection delivered 30 days after SPS can reduce these symptoms. Olfactory and auditory cues were added to the SPS context and reactivity to these cues were tested more than one month later using an odor discrimination test, and freezing to the trauma-related tone. Other PTSD symptoms, such as anxiety (elevated plus maze) and hyperarousal (acoustic startle response), were also investigated in these rats.
Some behavioural reactivity to the environmental cues was observed in rats exposed to SPS. However, a subgroup of these rats showed an exaggerated disruption in performance in 3 to 4 of the behavioral tests relative to controls, suggesting that two classes of rats, those that are susceptible and those that are resilient to SPS, can be dissociated. When rats were treated with amphetamine (1mg/kg) injected in the SPS context 30 days after SPS, traumatized rats no longer differed from their corresponding controls and all were identified as resilient. The present data demonstrated that rats exposed to SPS can be either susceptible or resilient and a single amphetamine injection can abolish the associated symptoms. We propose that combining memory reactivation, with an amphetamine-induced positive mood, can modify the emotional valence of the initial memory, inducing long-lasting remodeling of the traumatic memory, thereby opening a novel therapeutic avenue.
Memory reactivation is an important process resulting from reexposure to salient training-related information whereby a memory is brought from an inactive to an active state. Reactivation is the ...first stage of memory retrieval but can result from the exposure to salient cues without any behavioral output. Such cue-induced reactivation, although frequently used by neuroscientists to study reconsolidation, has seldom been considered as a process in its own right and studied as such. This review presents arguments indicating that memory reactivation has two main consequences: (1) to enhance the accessibility of the target memory and (2) to make the memory malleable. Accordingly, reactivation creates a transient state during which the content of the memory is easily accessible and can be modified and/or updated. As both of these aspects can be observed shortly after memory reactivation, this review emphasizes that reconsolidation is not necessarily required for these processes and calls attention to reactivation as a factor in the dynamics of the memory.
•Post-training hippocampal lesions can be understood as a contextual change.•Contextual change effects mimic time-dependent effects of hippocampal lesions.•Temporally graded retrograde amnesia is not ...specific for episodic/contextual memory.•Consolidation concept needs to be revisited.
For more than 50 years, knowledge of memory processes has been based on the consolidation hypothesis, which postulates that new memories require time to become stabilized. Two forms of the consolidation model exist. The Cellular Consolidation concept is based upon retrograde amnesia induced by amnesic treatments, the severity of which decreases as the learning to treatment increases over minutes or hours. In contrast, The Systems Consolidation model is based on post-training hippocampal lesions, which produce more severe retrograde amnesia when induced after days than after weeks. Except for the temporal parameters, Cellular and Systems Consolidation show many similarities. Here we propose that Systems consolidation, much as Cellular Consolidation (see Gisquet- Verrier and Riccio, 2018), can be explained in terms of a form of state-dependency. Accordingly, lesions of the hippocampus induce a change in the internal state of the animal, which disrupts retrieval processes. But the effect of contextual change is known to decrease with the length of the retention intervals, consistent with time-dependent retrograde amnesia. We provide evidence supporting this new view.
Active (new and reactivated) memories are considered to be labile and sensitive to treatments disrupting the time-dependent consolidation/reconsolidation processes required for their stabilization. ...Active memories also allow the integration of new information for updating memories. Here, we investigate the possibility that, when active, the internal state provided by amnesic treatments is represented and integrated within the initial memory and that amnesia results from the absence of this state at testing. We showed in rats that the amnesia resulting from systemic, intracerebroventricular and intrahippocampal injections of the protein synthesis inhibitor cycloheximide, administered after inhibitory avoidance training or reactivation, can be reversed by a reminder, including re-administration of the same drug. Similar results were obtained with lithium chloride (LiCl), which does not affect protein synthesis, when delivered systemically after training or reactivation. However, LiCl can induce memory given that a conditioned taste aversion was obtained for a novel taste, presented just before conditioning or reactivation. These results indicate that memories can be established and maintained without de novo protein synthesis and that experimental amnesia may not result from a disruption of memory consolidation/reconsolidation. The findings more likely support the integration hypothesis: posttraining/postreactivation treatments induce an internal state, which becomes encoded with the memory, and should be present at the time of testing to ensure a successful retrieval. This integration concept includes most of the previous explanations of memory recovery after retrograde amnesia and critically challenges the traditional memory consolidation/reconsolidation hypothesis, providing a more dynamic and flexible view of memory.
This study provides evidence challenging the traditional consolidation/reconsolidation hypotheses that have dominated the literature over the past 50 years. Based on amnesia studies, that hypothesis states that active (i.e., new and reactivated) memories are similarly labile and (re)established in a time-dependent manner within the brain through processes that require de novo protein synthesis. Our data show that new/reactivated memories can be formed without protein synthesis and that amnesia can be induced by drugs that do not affect protein synthesis. We propose that amnesia results from memory integration of the internal state produced by the drug that is subsequently necessary for retrieval of the memory. This interpretation gives a dynamic view of memory, rapidly stored and easily updated when active.
Abstract Supporting our hypothesis of common biological bases for post-traumatic stress disorder (PTSD) and addiction, we recently reported that rats exposed to a single prolonged stress (SPS), a ...PTSD model, develop a delayed behavioral sensitization of the noradrenergic system, similar to that observed in mice after four repeated drug administrations. However, sensitization after trauma was modulated by reactivity to novelty, and this aspect that had not been explored in the addiction model. The first aim of the paper was thus to investigate the influence of reactivity to novelty on delayed behavioral sensitization in rats after four repeated amphetamine injections. Injections were either distributed over 4 days, as conducted in mouse models of addiction, or massed during a single session, reproducing SPS conditions. The second aim was to investigate whether repeated amphetamine injections have similar behavioral consequences to those induced by PTSD. Our results showed that massed amphetamine injections induced more anxiety than distributed injections, and led to avoidance of drug-associated cues avoidance, while distributed injections somewhat reduced the startle response, such as is seen in SPS. In addition, massed amphetamine injections induced a delayed behavioral sensitization clearly affected by the reactivity to novelty, reproducing results observed following exposure to traumatic events. Finally, all rats receiving repeated amphetamine injections exhibited a behavioral sensitization in response to exposure to drug-associated cues. Taken together, these data strengthen the position that drug addiction and PTSD share some common mechanisms that we tried to clarify in this paper.
Effects of neurotoxic lesions of the
prelimbic-infralimbic cortex (PL-IL) were examined in
rats performing 2 conditional tasks. PL-IL-lesioned rats
showed normal acquisition of a visuospatial ...conditional
discrimination in a Y maze as well as a tone-light conditional
discrimination in an operant chamber, indicating that the
PL-IL is not necessary for response selection processes. When
the working memory load was subsequently increased in the
tone-light conditional discrimination, rats with PL-IL
lesions showed a delay-dependent disruption of performance. This
suggests a role of the PL-IL in some working memory processes.
However, the present results, considered along with previous
studies, suggest that the PL-IL does not seem to be directly
involved in the processes necessary to maintain specific items over
a delay period but rather in the planning of forthcoming behavioral
responses on the basis of previously acquired information.
The aim of this study was to demonstrate the potential of a wireless pixelated β+-sensitive intracerebral probe (PIXSIC) for in vivo positron emission tomographic (PET) radiopharmacology in awake and ...freely moving rodents. The binding of 11Craclopride to D2 dopamine receptors was measured in anesthetized and awake rats following injection of the radiotracer. Competitive binding was assessed with a cold raclopride injection 20 minutes later. The device can accurately monitor binding of PET ligands in freely moving rodents with a high spatiotemporal resolution. Reproducible time-activity curves were obtained for pixels throughout the striatum and cerebellum. A significantly lower 11Craclopride tracer-specific binding was observed in awake animals. These first results pave the way for PET tracer pharmacokinetics measurements in freely moving rodents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Contrary to human and primate, working memory in the rodent is usually considered as a simple short term memory buffer and mainly investigated using delayed response paradigms. The aim of the present ...study was to further investigate the role of the rat prelimbic/infralimbic cortex in different spatial delayed tasks in order to dissociate its involvement in temporary storage from other information processes, such as behavioral flexibility and attention. In experiment 1 rats were trained in a standard elimination win-shift task in a radial-arm maze after which a 1-min delay was inserted mid trial. Prelimbic/infralimbic lesions induced only a transient disruption of performance following introduction of the delay. In experiment 2, rats were trained directly in a win-shift task with a 5-min delay that was subsequently extended to 30 min. Prelimbic/infralimbic lesions did not significantly affect behavior. Nevertheless, transient disruptions of performance (correlated with lesion extent) were noted repeatedly in lesioned rats when sets of interfering events were presented. The present findings indicate that prelimbic/infralimbic cortex is not directly involved in the short term maintenance of specific information but is implicated when changes, such as sudden introduction of a delay or exposure to unexpected interfering events, alter the initial situation. It appears that working memory in rodents should be considered, as in humans and primates, to encompass both storage and monitoring functions. The present results along with previous ones strongly suggest that prelimbic/infralimbic cortex is not involved in the temporary on-line storage but rather in the control of information required to prospectively organize the ongoing action.
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