Anteromedial thalamus gates the selection and stabilization of long-term memories.

Memories initially formed in hippocampus gradually stabilize to cortex over weeks-to-months for long-term storage. The mechanistic details of this brain re-organization remain poorly understood. We recorded bulk neural activity in circuits that link hippocampus and cortex as mice performed a memory-guided virtual-reality task over weeks. We identified a prominent and sustained neural correlate of memory in anterior thalamus, whose inhibition substantially disrupted memory consolidation. More strikingly, gain amplification enhanced consolidation of otherwise unconsolidated memories. To gain mechanistic insights, we developed a technology for simultaneous cellular-resolution imaging of hippocampus, thalamus, and cortex throughout consolidation. We found that whereas hippocampus equally encodes multiple memories, the anteromedial thalamus preferentially encodes salient memories, and gradually increases correlations with cortex to facilitate tuning and synchronization of cortical ensembles. We thus identify a thalamo-cortical circuit that gates memory consolidation and propose a mechanism suitable for the selection and stabilization of hippocampal memories into longer-term cortical storage.

Dissociated Role of Thalamic and Cortical Input to the Lateral Amygdala for Consolidation of Long-Term Fear Memory.

Post-encoding coordinated reactivation of memory traces distributed throughout interconnected brain regions is thought to be critical for consolidation of memories. However, little is known about the role of neural circuit pathways during post-learning periods for consolidation of memories. To investigate this question, we optogenetically silenced the inputs from both auditory cortex and thalamus in the lateral amygdala (LA) for 15 min immediately following auditory fear conditioning (FC) and examined its effect on fear memory formation in mice of both sexes. Optogenetic inhibition of both inputs disrupted long-term fear memory formation tested 24 h after FC. This effect was specific such that the same inhibition did not affect short-term memory and context-dependent memory. Moreover, long-term memory was intact if the inputs were inhibited at much later time points after FC (3 h or 1 d after FC), indicating that optical inhibition for 15 min itself does not produce any nonspecific deleterious effect on fear memory retrieval. Selective inhibition of thalamic input was sufficient to impair consolidation of auditory fear memory. In contrast, selective inhibition of cortical input disrupted remote fear memory without affecting recent memory. These results reveal a dissociated role of thalamic and cortical input to the LA during early post-learning periods for consolidation of long-term fear memory.SIGNIFICANCE STATEMENT Coordinated communications between brain regions are thought to be essential during post-learning periods for consolidation of memories. However, the role of specific neural circuit pathways in this process has been scarcely explored. Using a precise optogenetic inhibition of auditory input pathways, either thalamic or cortical or both, to the LA during post-training periods, we here show that thalamic input is required for consolidation of both recent and remote fear memory, whereas cortical input is crucial for consolidation of remote fear memory. These results reveal a dissociated role of auditory input pathways to the LA for consolidation of long-term fear memory.

Neurofeedback training improves episodic and semantic long-term memory performance.

Understanding and improving memory are vital to enhance human life. Theta rhythm is associated with memory consolidation and coding, but the trainability and effects on long-term memory of theta rhythm are unknown. This study investigated the ability to improve long-term memory using a neurofeedback (NFB) technique reflecting the theta/low-beta power ratio on an electroencephalogram (EEG). Our study consisted of three stages. First, the long-term memory of participants was measured. In the second stage, the participants in the NFB group received 3 days of theta/low-beta NFB training. In the third stage, the long-term memory was measured again. The NFB group had better episodic and semantic long-term memory than the control group and significant differences in brain activity between episodic and semantic memory during the recall tests were revealed. These findings suggest that it is possible to improve episodic and semantic long-term memory abilities through theta/low-beta NFB training.

Disengagement of Motor Cortex during Long-Term Learning Tracks the Performance Level of Learned Movements.

Not all movements require the motor cortex for execution. Intriguingly, dependence on motor cortex of a given movement is not fixed, but instead can dynamically change over the course of long-term learning. For instance, rodent forelimb movements that initially require motor cortex can become independent of the motor cortex after an extended period of training. However, it remains unclear whether long-term neural changes rendering the motor cortex dispensable are a simple function of the training length. To address this issue, we trained mice (both male and female) to perform two distinct forelimb movements, forward versus downward reaches with a joystick, concomitantly over several weeks, and then compared the involvement of the motor cortex between the two movements. Most mice achieved different levels of motor performance between the two movements after long-term training. Of the two movements, the one that achieved higher trial-to-trial consistency (i.e., consistent-direction movement) was significantly less affected by inactivation of motor cortex than the other (i.e., variable-direction movement). Two-photon calcium imaging of motor cortical neurons revealed that the consistent-direction movement activates fewer neurons, producing weaker and less consistent population activity than the variable-direction movement. Together, the motor cortex was less engaged and less necessary for learned movements that achieved higher levels of consistency. Thus, the long-term reorganization of neural circuits that frees the motor cortex from the learned movement is not a mere function of training length. Rather, this reorganization tracks the level of motor performance that the animal achieves during training.SIGNIFICANCE STATEMENT Long-term training of a movement reshapes motor circuits, disengaging motor cortex potentially for automatized execution of the learned movement. Acquiring new motor skills often involves learning of multiple movements (e.g., forehand and backhand strokes when learning tennis), but different movements do not always improve at the same time nor reach the same level of proficiency. Here we showed that the involvement of motor cortex after long-term training differs between similar yet distinct movements that reached different levels of expertise. Motor cortex was less engaged and less necessary for the more proficient movement. Thus, disengagement of motor cortex is not a simple function of training time, but instead tracks the level of expertise of a learned movement.

A thalamo-amygdalar circuit underlying the extinction of remote fear memories.

Fear and trauma generate some of the longest-lived memories. Despite the corresponding need to understand how such memories can be attenuated, the underlying brain circuits remain unknown. Here, combining viral tracing, neuronal activity mapping, fiber photometry, chemogenetic and closed-loop optogenetic manipulations in mice, we show that the extinction of remote (30-day-old) fear memories depends on thalamic nucleus reuniens (NRe) inputs to the basolateral amygdala (BLA). We found that remote, but not recent (1-day-old), fear extinction activates NRe-to-BLA inputs, which become potentiated upon fear reduction. Furthermore, both monosynaptic NRe-to-BLA and total NRe activity increase shortly before freezing cessation, suggesting that the NRe registers and transmits safety signals to the BLA. Accordingly, pan-NRe and pathway-specific NRe-to-BLA inhibition impairs, whereas their activation facilitates, remote fear extinction. These findings identify the NRe as a crucial BLA regulator for extinction and provide the first functional description of the circuits underlying the attenuation of consolidated fear memories.

Brd4 participates in epigenetic regulation of the extinction of remote auditory fear memory.

BACKGROUND: Inaccurate fear memories can be maladaptive and potentially portrait a core symptomatic dimension of fear adaptive disorders such as post-traumatic stress disorder (PTSD), which is generally characterized by an intense and enduring memory for the traumatic events. Evidence exists in support of epigenetic regulation of fear behavior. Brd4, a member of the bromodomain and extra-terminal domain (BET) protein family, serves as a chromatin "reader" by binding to histones in acetylated lysine residues, and hence promotes transcriptional activities. However, less is known whether Brd4 participates in modulating cognitive activities especially memory formation and extinction. Here we provide evidence for a role of Brd4 in modulation of auditory fear memory. Auditory fear conditioning resulted in a biphasic Brd4 activation in the anterior cingulate cortex (ACC) and hippocampus of adult mice. Thus, Brd4 phosphorylation occurred 6 h and 3-14 days, respectively, after auditory fear conditioning. Systemic inhibition of Brd4 with a BET inhibitor, JQ1, impaired the extinction of remote (i.e., 14 days after conditioning) fear memory. Further, conditional Brd4 knockout in excitatory neurons of the forebrain impaired remote fear extinction as observed in the JQ1-treated mice. Herein, we identified that Brd4 is essential for extinction of remote fear in rodents. These results thus indicate that Brd4 potentially plays a role in the pathogenesis of PTSD.

Guanosine protects against behavioural and mitochondrial bioenergetic alterations after mild traumatic brain injury.

Traumatic brain injury (TBI) constitutes a heterogeneous cerebral insult induced by traumatic biomechanical forces. Mitochondria play a critical role in brain bioenergetics, and TBI induces several consequences related with oxidative stress and excitotoxicity clearly demonstrated in different experimental model involving TBI. Mitochondrial bioenergetics alterations can present several targets for therapeutics which could help reduce secondary brain lesions such as neuropsychiatric problems, including memory loss and motor impairment. Guanosine (GUO), an endogenous neuroprotective nucleoside, affords the long-term benefits of controlling brain neurodegeneration, mainly due to its capacity to activate the antioxidant defense system and maintenance of the redox system. However, little is known about the exact protective mechanism exerted by GUO on mitochondrial bioenergetics disruption induced by TBI. Thus, the aim of this study was to investigate the effects of GUO in brain cortical and hippocampal mitochondrial bioenergetics in the mild TBI model. Additionally, we aimed to assess whether mitochondrial damage induced by TBI may be related to behavioral alterations in rats. Our findings showed that 24 h post-TBI, GUO treatment promotes an adaptive response of mitochondrial respiratory chain increasing oxygen flux which it was able to protect against the uncoupling of oxidative phosphorylation (OXPHOS) induced by TBI, restored the respiratory electron transfer system (ETS) established with an uncoupler. Guanosine treatment also increased respiratory control ratio (RCR), an indicator of the state of mitochondrial coupling, which is related to the mitochondrial functionality. In addition, mitochondrial bioenergetics failure was closely related with locomotor, exploratory and memory impairments. The present study suggests GUO treatment post mild TBI could increase GDP endogenous levels and consequently increasing ATP levels promotes an increase of RCR increasing OXPHOS and in substantial improve mitochondrial respiration in different brain regions, which, in turn, could promote an improvement in behavioral parameters associated to the mild TBI. These findings may contribute to the development of future therapies with a target on failure energetic metabolism induced by TBI.

Long-Term Value Memory in the Primate Posterior Thalamus for Fast Automatic Action.

The thalamus is known to process information from various brain regions and relay it to other brain regions, serving an essential role in sensory perception and motor execution. The thalamus also receives inputs from basal ganglia nuclei (BG) involved in value-based decision making, suggesting a role in the value process. We found that neurons in a particular area of the rhesus macaque posterior thalamus encoded the historical value memory of visual objects. Many of these value-coding neurons were located in the suprageniculate nucleus (SGN). This thalamic area directly received anatomical input from the superior colliculus (SC), and the neurons showed visual responses with contralateral preferences. Notably, the value discrimination activity of these thalamic neurons increased during learning, with the learned values stably retained even more than 200 days after learning. Our data indicate that single neurons in the posterior thalamus not only processed simple visual information but also represented historical values. Furthermore, our data suggest an SC-posterior thalamus-BG-SC subcortical loop circuit that encodes the historical value, enabling a quick automatic gaze by bypassing the visual cortex.

A novelty-retrieval-extinction paradigm leads to persistent attenuation of remote fear memories.

Exposure to a novel environment can enhance the extinction of recent contextual fear in mice. This has been explained by a tagging and capture hypothesis. Consistently, we show in mice that exposure to a novel environment before extinction training promoted the extinction of recent auditory fear. However, such a promoting effect of novelty was absent for remote memories. In the present study, we replaced the regular extinction training with a retrieval-extinction session which capitalized on a reconsolidation window. When novelty exposure was followed by a retrieval-extinction session, remote fear was distinguished more easily and permanently. We have termed it as a "novelty-retrieval-extinction" paradigm. This paradigm played a greater role in the extinction of remote fear when fear conditioning and retrieval-extinction occurred in two different contexts other than in one identical context. The mechanism underlying the facilitating effect of this paradigm might involve up-regulation of histone acetylation in the hippocampus, which has been reported to increase functional and structural neuroplasticity. The present work proposes an effective, drug-free paradigm for the extinction of remote fear, which could be easily adapted in humans with least side effects.

Tracking Your Mind's Eye during Recollection: Decoding the Long-Term Recall of Short Audiovisual Clips.

Unlike familiarity, recollection involves the ability to reconstruct mentally previous events that results in a strong sense of reliving. According to the reinstatement hypothesis, this specific feature emerges from the reactivation of cortical patterns involved during information exposure. Over time, the retrieval of specific details becomes more difficult, and memories become increasingly supported by familiarity judgments. The multiple trace theory (MTT) explains the gradual loss of episodic details by a transformation in the memory representation, a view that is not shared by the standard consolidation model. In this study, we tested the MTT in light of the reinstatement hypothesis. The temporal dynamics of mental imagery from long-term memory were investigated and tracked over the passage of time. Participant EEG activity was recorded during the recall of short audiovisual clips that had been watched 3 weeks, 1 day, or a few hours beforehand. The recall of the audiovisual clips was assessed using a Remember/Know/New procedure, and snapshots of clips were used as recall cues. The decoding matrices obtained from the multivariate pattern analyses revealed sustained patterns that occurred at long latencies (>500 msec poststimulus onset) that faded away over the retention intervals and that emerged from the same neural processes. Overall, our data provide further evidence toward the MTT and give new insights into the exploration of our "mind's eye."

Self-regulation of brain activity and its effect on cognitive function in patients with multiple sclerosis - First insights from an interventional study using neurofeedback.

OBJECTIVE: To investigate the effects of EEG-based neurofeedback training, in which one can learn to self-regulate one's own brain activity, on cognitive function in patients with multiple sclerosis (pwMS). METHODS: Fourteen pwMS performed ten neurofeedback training sessions within 3-4 weeks at home using a tele-rehabilitation system. The aim of the neurofeedback training was to increase voluntarily the sensorimotor rhythm (SMR, 12-15 Hz) in the EEG over central brain areas by receiving visual real-time feedback thereof. Cognitive function was assessed before and after all neurofeedback training sessions using a comprehensive standardized neuropsychological test battery. RESULTS: Half of the pwMS (N = 7) showed cognitive improvements in long-term memory and executive functions after neurofeedback training. These patients successfully learned to self-regulate their own brain activity by means of neurofeedback training. The other half of pwMS (N = 7) did neither show any cognitive changes when comparing the pre- and post-assessment nor were they able to modulate their own brain activity in the desired direction during neurofeedback training. CONCLUSIONS: Data from this interventional study provide first preliminary evidence that successful self-regulation of one's own brain activity may be associated with cognitive improvements in pwMS. SIGNIFICANCE: These promising results should stimulate further studies. Neurofeedback might be a promising and alternative tool for future cognitive rehabilitation.

Impairments in remote memory caused by the lack of Type 2 IP3 receptors.

The second messenger inositol 1,4,5-trisphosphate (IP3 ) is paramount for signal transduction in biological cells, mediating Ca2+ release from the endoplasmic reticulum. Of the three isoforms of IP3 receptors identified in the nervous system, Type 2 (IP3 R2) is the main isoform expressed by astrocytes. The complete lack of IP3 R2 in transgenic mice was shown to significantly disrupt Ca2+ signaling in astrocytes, while leaving neuronal intracellular pathways virtually unperturbed. Whether and how this predominantly nonneuronal receptor might affect long-term memory function has been a matter of intense debate. In this work, we found that the absence of IP3 R2-mediated signaling did not disrupt normal learning or recent (24-48 h) memory. Contrary to expectations, however, mice lacking IP3 R2 exhibited remote (2-4 weeks) memory deficits. Not only did the lack of IP3 R2 impair remote recognition, fear, and spatial memories, but it also prevented naturally occurring post-encoding memory enhancements consequent to memory consolidation. Consistent with the key role played by the downscaling of synaptic transmission in memory consolidation, we found that NMDAR-dependent long-term depression was abnormal in ex vivo hippocampal slices acutely prepared from IP3 R2-deficient mice, a deficit that could be prevented upon supplementation with D-serine - an NMDA-receptor co-agonist whose synthesis depends upon astrocytes' activity. Our results reveal that IP3 R2 activation, which in the brain is paramount for Ca2+ signaling in astrocytes, but not in neurons, can help shape brain plasticity by enhancing the consolidation of newly acquired information into long-term memories that can guide remote cognitive behaviors.

Neurofeedback helps to reveal a relationship between context reinstatement and memory retrieval.

Theories of mental context and memory posit that successful mental context reinstatement enables better retrieval of memories from the same context, at the expense of memories from other contexts. To test this hypothesis, we had participants study lists of words, interleaved with task-irrelevant images from one category (e.g., scenes). Following encoding, participants were cued to mentally reinstate the context associated with a particular list, by thinking about the images that had appeared between the words. We measured context reinstatement by applying multivariate pattern classifiers to fMRI, and related this to performance on a free recall test that followed immediately afterwards. To increase sensitivity, we used a closed-loop neurofeedback procedure, whereby higher classifier evidence for the cued category elicited increased visibility of the images from the studied context onscreen. Our goal was to create a positive feedback loop that amplified small fluctuations in mental context reinstatement, making it easier to experimentally detect a relationship between context reinstatement and recall. As predicted, we found that greater amounts of classifier evidence were associated with better recall of words from the reinstated context, and worse recall of words from a different context. In a second experiment, we assessed the role of neurofeedback in identifying this brain-behavior relationship by presenting context images again and manipulating whether their visibility depended on classifier evidence. When neurofeedback was removed, the relationship between classifier evidence and memory retrieval disappeared. Together, these findings demonstrate a clear effect of context reinstatement on memory recall and suggest that neurofeedback can be a useful tool for characterizing brain-behavior relationships.

"Looking-at-nothing" during sequential sensorimotor actions: Long-term memory-based eye scanning of remembered target locations.

Before acting humans saccade to a target object to extract relevant visual information. Even when acting on remembered objects, locations previously occupied by relevant objects are fixated during imagery and memory tasks - a phenomenon called "looking-at-nothing". While looking-at-nothing was robustly found in tasks encouraging declarative memory built-up, results are mixed in the case of procedural sensorimotor tasks. Eye-guidance to manual targets in complete darkness was observed in a task practiced for days beforehand, while investigations using only a single session did not find fixations to remembered action targets. Here, it is asked whether looking-at-nothing can be found in a single sensorimotor session and thus independent from sleep consolidation, and how it progresses when visual information is repeatedly unavailable. Eye movements were investigated in a computerized version of the trail making test. Participants clicked on numbered circles in ascending sequence. Fifty trials were performed with the same spatial arrangement of 9 visual targets to enable long-term memory consolidation. During 50 consecutive trials, participants had to click the remembered target sequence on an empty screen. Participants scanned the visual targets and also the empty target locations sequentially with their eyes, however, the latter less precise than the former. Over the course of the memory trials, manual and oculomotor sequential target scanning became more similar to the visual trials. Results argue for robust looking-at-nothing during procedural sensorimotor tasks provided that long-term memory information is sufficient.

Long-term pitch memory for music recordings is related to auditory working memory precision.

Most individuals have reliable long-term memories for the pitch of familiar music recordings. This pitch memory (1) appears to be normally distributed in the population, (2) does not depend on explicit musical training and (3) only seems to be weakly related to differences in listening frequency estimates. The present experiment was designed to assess whether individual differences in auditory working memory could explain variance in long-term pitch memory for music recordings. In Experiment 1, participants first completed a musical note adjustment task that has been previously used to assess working memory of musical pitch. Afterward, participants were asked to judge the pitch of well-known music recordings, which either had or had not been shifted in pitch. We found that performance on the pitch working memory task was significantly related to performance in the pitch memory task using well-known recordings, even when controlling for overall musical experience and familiarity with each recording. In Experiment 2, we replicated these findings in a separate group of participants while additionally controlling for fluid intelligence and non-pitch-based components of auditory working memory. In Experiment 3, we demonstrated that participants could not accurately judge the pitch of unfamiliar recordings, suggesting that our method of pitch shifting did not result in unwanted acoustic cues that could have aided participants in Experiments 1 and 2. These results, taken together, suggest that the ability to maintain pitch information in working memory might lead to more accurate long-term pitch memory.

Formation of Long-Term Locomotor Memories Is Associated with Functional Connectivity Changes in the Cerebellar-Thalamic-Cortical Network.

Although motor adaptation is typically rapid, accumulating evidence shows that it is also associated with long-lasting behavioral and neuronal changes. Two processes were suggested to explain the formation of long-term motor memories: recall, reflecting a retrieval of previous motor actions, and faster relearning, reflecting an increased sensitivity to errors. Although these manifestations of motor memories were initially demonstrated in the context of adaptation experiments in reaching, indications of long-term motor memories were also demonstrated recently in other kinds of adaptation such as in locomotor adaptation. Little is known about the neural processes that underlie these distinct aspects of memory. We hypothesize that recall and faster relearning reflect different learning processes that operate at the same time and depend on different neuronal networks. Seventeen subjects performed a multisession locomotor adaptation experiment in the laboratory, together with resting-state and localizer fMRI scans, after the baseline and the locomotor adaptation sessions. We report a modulation of the cerebellar-thalamic-cortical and cerebellar-basal ganglia networks after locomotor adaptation. Interestingly, whereas thalamic-cortical baseline connectivity was correlated with recall, cerebellar-thalamic baseline connectivity was correlated with faster relearning. Our results suggest that separate neuronal networks underlie error sensitivity and retrieval components. Individual differences in baseline resting-state connectivity can predict idiosyncratic combination of these components. SIGNIFICANCE STATEMENT: The ability to shape our motor behavior rapidly in everyday activity, such as when walking on sand, suggests the existence of long-term motor memories. It was suggested recently that this ability is achieved by the retrieval of previous motor actions and by enhanced relearning capacity. Little is known about the neural mechanisms that underlie these memory processes. We studied the modularity in long-term motor memories in the context of locomotor adaptation using resting-state fMRI. We show that retrieval and relearning effects are associated with separate locomotor control networks and that intersubject variability in learning and in the generation of motor memories could be predicted from baseline resting-state connectivity in locomotor-related networks.

Shifting visual perspective during retrieval shapes autobiographical memories.

The dynamic and flexible nature of memories is evident in our ability to adopt multiple visual perspectives. Although autobiographical memories are typically encoded from the visual perspective of our own eyes they can be retrieved from the perspective of an observer looking at our self. Here, we examined the neural mechanisms of shifting visual perspective during long-term memory retrieval and its influence on online and subsequent memories using functional magnetic resonance imaging (fMRI). Participants generated specific autobiographical memories from the last five years and rated their visual perspective. In a separate fMRI session, they were asked to retrieve the memories across three repetitions while maintaining the same visual perspective as their initial rating or by shifting to an alternative perspective. Visual perspective shifting during autobiographical memory retrieval was supported by a linear decrease in neural recruitment across repetitions in the posterior parietal cortices. Additional analyses revealed that the precuneus, in particular, contributed to both online and subsequent changes in the phenomenology of memories. Our findings show that flexibly shifting egocentric perspective during autobiographical memory retrieval is supported by the precuneus, and suggest that this manipulation of mental imagery during retrieval has consequences for how memories are retrieved and later remembered.

Information Retrieval during Free Listing Is Biased by Memory: Evidence from Medicinal Plants.

Free listing is a methodological tool that is widely used in various scientific disciplines. A typical assumption of this approach is that individual lists reflect a subset of total knowledge and that the first items listed are the most culturally important. However, little is known about how cognitive processes influence free lists. In this study, we assess how recent memory of use, autonoetic and anoetic memory, and long-term associative memory can affect the composition and order of items in free lists and evaluate whether free lists indicate the most important items. Based on a model of local knowledge about medicinal plants and their therapeutic targets, which was collected via individual semi-structured interviews, we classify each item recorded in free lists according to the last time that the item was used by the informant (recently or long ago), the type of relevant memory (autonoetic or anoetic memory) and the existing associations between therapeutic targets (similar or random). We find that individuals have a tendency to recall information about medicinal plants used during the preceding year and that the recalled plants were also the most important plants during this period. However, we find no trend in the recall of plants from long-term associative memory, although this phenomenon is well established in studies on cognitive psychology. We suggest that such evidence should be considered in studies that use lists of medicinal plants because this temporal cognitive limit on the retrieval of knowledge affects data interpretation.

Postischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy.

We reported that fish oil (FO) prevented the loss of spatial memory caused by transient, global cerebral ischemia (TGCI), provided the treatment covered the first days prior to and after ischemia. Continuing these studies, trained rats were subjected to TGCI, and FO was administered for 10days, with a time window of efficacy (TWE) of 4, 8 or 12h post-ischemia. Retrograde memory was assessed up to 43days after TGCI. In another experiment, ischemic rats received FO with a 4- or 12-h TWE, and dendritic density was assessed in the hippocampus and cerebral cortex. The brain lipid profile was evaluated in sham-operated and ischemic rats that were treated with FO or vehicle with a 4-h TWE. Ischemia-induced retrograde amnesia was prevented by FO administration that was initiated with either a 4- or 8-h TWE. Fish oil was ineffective after a 12-h TWE. Independent of the TWE, FO did not prevent ischemic neuronal death. In the hippocampus, but not cerebral cortex, TGCI-induced dendritic loss was prevented by FO with a 4-h TWE but not 12-h TWE. The level of docosahexaenoic acid almost doubled in the hippocampus in ischemic, FO-treated rats (4-h TWE). The data indicate that (i) the anti-amnesic effect of FO can be observed with a TWE of up to 8h, (ii) the stimulation of dendritic neuroplasticity may have contributed to this effect, and (iii) DHA in FO may be the main active constituent in FO that mediates the cognitive and neuroplasticity effects on TGCI.

Retrieving fear memories, as time goes by .

Research in fear conditioning has provided a comprehensive picture of the neuronal circuit underlying the formation of fear memories. In contrast, our understanding of the retrieval of fear memories is much more limited. This disparity may stem from the fact that fear memories are not rigid, but reorganize over time. To bring some clarity and raise awareness about the time-dependent dynamics of retrieval circuits, we review current evidence on the neuronal circuitry participating in fear memory retrieval at both early and late time points following auditory fear conditioning. We focus on the temporal recruitment of the paraventricular nucleus of the thalamus (PVT) for the retrieval and maintenance of fear memories. Finally, we speculate as to why retrieval circuits change with time, and consider the functional strategy of recruiting structures not previously considered as part of the retrieval circuit.