Rewarded extinction increases amygdalar connectivity and stabilizes long-term memory traces in the vmPFC

Neurobiological evidence in rodents indicates that threat extinction incorporates reward neurocircuitry. Consequently, incorporating reward associations with an extinction memory may be an effective strategy to persistently attenuate threat responses. Moreover, while there is considerable research on the short-term effects of extinction strategies in humans, the long-term effects of extinction are rarely considered. In a within-subjects fMRI study, we compared counterconditioning (a form of rewarded-extinction) to standard extinction, at recent (24 hours) and remote (~1 month) retrieval tests. Relative to standard extinction, counterconditioning diminished 24-hour relapse of arousal and threat expectancy, and reduced activity in brain regions associated with the appraisal and expression of threat (e.g., thalamus, insula, periaqueductal gray). The retrieval of reward-associated extinction memory was accompanied by functional connectivity between the amygdala and the ventral striatum, whereas the retrieval of standard-extinction memories was associated with connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). One-month later, the retrieval of both standard- and rewarded-extinction was associated with amygdala-vmPFC connectivity. However, only rewarded extinction created a stable memory trace in the vmPFC, identified through overlapping multivariate patterns of fMRI activity from extinction to 24-hour and 1-month retrieval. These findings provide new evidence that reward may generate a more stable and enduring memory trace of attenuated threat in humans.

Tracking induced forgetting across both strong and weak memory representations to test competing theories of forgetting

Here we employ a novel analysis to address the question: what causes induced forgetting of pictures? We use baseline memorability as a measure of initial memory strength to ask whether induced forgetting is due to (1) recognition practice damaging the association between the memory representation and the category cue used to activate the representation, (2) the updating of a memory trace by incorporating information about a memory probe presented during recognition practice to the stored trace, (3) inhibitory mechanisms used to resolve the conflict created when correctly selecting the practiced item activates competing exemplars, (4) a global matching model in which repeating some items will hurt memory for other items, or (5) falling into the zone of destruction, where a moderate amount of activation leads to the highest degree of forgetting. None of the accounts of forgetting tested here can comprehensively account for both the novel analyses reported here and previous data using the induced forgetting paradigm. We discuss aspects of forgetting theories that are consistent with the novel analyses and existing data, a potential solution for existing models, proposals for future directions, and considerations when incorporating memorability into models of memory.

Overtraining Strengthens the Visual Discrimination Memory Trace Outside the Hippocampus in Male Rats

The hippocampus (HPC) may compete with other memory systems when establishing a representation, a process termed overshadowing. However, this overshadowing may be mitigated by repeated learning episodes, making a memory resistant to post-training hippocampal damage. In the current study, we examined this overshadowing process for a hippocampal-dependent visual discrimination memory in rats. In Experiment 1, male rats were trained to criterion (80% accuracy on two consecutive days) on a visual discrimination and then given 50 additional trials distributed over 5 days or 10 weeks. Regardless of this additional learning, extensive damage to the HPC caused retrograde amnesia for the visual discrimination, suggesting that the memory remained hippocampal-dependent. In Experiment 2, rats received hippocampal damage before learning and required approximately twice as many trials to acquire the visual discrimination as control rats, suggesting that, when the overshadowing or competition is removed, the non-hippocampal memory systems only slowly acquires the discrimination. In Experiment 3, increasing the additional learning beyond criterion by 230 trials, the amount needed in Experiment 2 to train the non-hippocampal systems in absence of competition, successfully prevented the retrograde amnesic effects of post-training hippocampal damage. Combined, the findings suggest that a visual discrimination memory trace can be strengthened in non-hippocampal systems with overtraining and become independent of the HPC.

Lateral entorhinal cortex suppresses drift in cortical memory representations.

Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the LEC's activity for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the LEC's efferent targets, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer's disease.

Mechanisms of Memory Updating: State Dependency vs. Reconsolidation

Reactivating a memory trace has been argued to put it in a fragile state where it must undergo a stabilization process known as reconsolidation. During this process, memories are thought to be susceptible to interference and can be updated with new information. In the spatial context paradigm, memory updating has been shown to occur when new information is presented in the same spatial context as old information, an effect attributed to a reconsolidation process. However, the integration concept holds that memory change can only occur when reactivation and test states are the same, similar to a state-dependent effect. Thus, in human episodic memory, memory updating should only be found when state is the same across the study, reactivation, and test sessions. We investigated whether memory updating can be attributed to state dependency in two experiments using mood as a state. We found evidence of memory updating only when mood was the same across all sessions of the experiments, lending support to the integration concept and posing a challenge to a reconsolidation explanation.

Mnemonic prediction errors promote detailed memories

When our experience violates our predictions, it is adaptive to update our knowledge to promote a more accurate representation of the world and facilitate future predictions. Theoretical models propose that these mnemonic prediction errors should be encoded into a distinct memory trace to prevent interference with previous, conflicting memories. We investigated this proposal by repeatedly exposing participants to pairs of sequentially presented objects (A → B), thus evoking expectations. Then, we violated participants’ expectations by replacing the second object in the pairs with a novel object (A → C). The following item memory test required participants to discriminate between identical old items and similar lures, thus testing detailed and distinctive item memory representations. In two experiments, mnemonic prediction errors enhanced item memory: Participants correctly identified more old items as old when those items violated expectations during learning, compared with items that did not violate expectations. This memory enhancement for C items was only observed when participants later showed intact memory for the related A → B pairs, suggesting that strong predictions are required to facilitate memory for violations. Following up on this, a third experiment reduced prediction strength prior to violation and subsequently eliminated the memory advantage of violations. Interestingly, mnemonic prediction errors did not increase gist-based mistakes of identifying old items as similar lures or identifying similar lures as old. Enhanced item memory in the absence of gist-based mistakes suggests that violations enhanced memory for items’ details, which could be mediated via distinct memory traces. Together, these results advance our knowledge of how mnemonic prediction errors promote memory formation.

Evaluation of the Activity of Choline Acetyltransferase From Different Synaptosomal Fractions at the Distinct Stages of Spatial Learning in the Morris Water Maze

Accumulated data have evidenced that brain cholinergic circuits play a crucial role in learning and memory; however, our knowledge about the participation of neocortical and hippocampal cholinergic systems in spatial learning needs to be refined. The aim of this study was to evaluate the association of the activity of membrane-bound and soluble choline acetyltransferase (ChAT) in the synaptosomal sub-fractions of the neocortex and hippocampus with performance of the spatial navigation task in the Morris water maze at different temporal stages of memory trace formation. To identify distinct stages of memory formation, rats were trained using a 5-day protocol with four trials per day. The mean escape latency for each trial was collected, and the entire dataset was subjected to principal component analysis. Based on the Morris water maze protocol, there were three relatively distinct stages of memory formation: days 1–2, day 3, and days 4–5. The remotely stored memory trace tested in repeated and reversal learning beginning on day 19 (14 days after the end of initial learning) was associated at the individual level mainly with performance during the second trial on day 21 (the third day or repeated or reversal learning). The ChAT activity data suggest the participation of cortical cholinergic projections mainly in the first stage of spatial learning (automatic sensory processing) and the involvement of hippocampal interneurons in the second stage (error-corrected learning). Cholinergic cortical interneurons participated mainly in the stage of asymptotic performance (days 4–5). It is advisable to evaluate other signalling pathways at the identified stages of memory formation.

Dynamical behaviors in the FitzHugh–Nagumo system with a memory trace

In this paper, the dynamical behaviors of the FitzHugh–Nagumo (FHN) system with a memory trace, which has time-fractional derivatives, are investigated. For the case of a classical order, the constant input current can change the stability of the equilibrium point in a single FHN unit, and the equilibrium is unstable in a certain range of the current. A decrease of the order of the time-fractional derivative may lead to a linear reduction of the range and the appearance of a solution of mixed-mode oscillations, which consist of subthreshold small-amplitude oscillation and suprathreshold large-amplitude oscillation. In the parameter space of the input current and the fractional order, the region of existing the mixed-mode oscillation is linearly widened when the fractional order moves toward its small value. If a suprathreshold perturbation is periodically applied, there exist some obvious bands, on which the excited period is locked to the perturbation period according to some rational ratios. As a result, the bands can be narrowed by decreasing the value of fractional order and their location has a slight drift toward the small value of the perturbation period. In addition, the properties of solitary traveling waves and wave train solutions are also studied in the one-dimensional space. It is illustrated that the traveling pulse is wider for a smaller value of fractional order, and its velocity is larger. Further, some relations of wave trains have a great change when the value of the fractional order is changed.