Ameliorative potential of ethanol extract of Calyptrochilum emarginatum leaves on scopolamine-induced amnesia in male swiss mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Calyptrochilum emarginatum (Afzel. Ex Sw.) Schltr. (Orchidaceae) is a traditional medicinal plant known for its antimicrobial properties and efficacy in managing convulsive fever and menstrual disorders and addressing conditions such as malaria, tuberculosis, and cough. AIM OF THE STUDY: The study aims to examine the memory-enhancing and neuroprotective properties of ethanol extract of Calyptrochilum emarginatum leaves (EECEL) in scopolamine-induced amnesia mice model. MATERIALS AND METHODS: Forty-two male mice were divided into six groups (n = 7). Group 1 served as control, administered distilled water (10 mL/kg, p. o), group 2 received scopolamine only (3 mg/kg, i. p.), groups 3 to 6 received pretreatments of EECEL (50, 100, and 200 mg/kg, p. o.) and donepezil (1 mg/kg, p. o.) 30 min before scopolamine (3 mg/kg), for seven days. Following treatments, behavioral (learning and memory) assessments were carried out, while biochemical (acetylcholinesterase activity, oxidative stress markers, inflammatory cytokines markers) and histological evaluations were done after euthanasia. RESULTS: Scopolamine significantly impaired spatial, long term and recognition memory. Nevertheless, administration of EECEL (50, 100, and 200 mg/kg orally) enhanced memory function in mice, as observed in the Y maze [F (5, 30) = 20.23, p < 0.0001], Morris water maze [F (10, 90) = 3.105, p = 0.0019; [F (5, 30) = 21.13, p < 0.0001]], and novel object recognition tasks [F (5, 30) = 37.22, p < 0.0001)]. Scopolamine-treated mice exhibited significant dysfunction in the cholinergic system, as evidenced by elevated AChE activity [0.099 ± 0.005 vs. 0.063 ± 0.004 mol/min/g] with an elevation in oxidative stress. On the other hand, administration of EECEL counteracted these consequences by reducing AChE activity, mitigating oxidative damage, reducing pro-inflammatory cytokines, and preventing degeneration of neurons. CONCLUSION: The results demonstrated that EECEL effectively mitigates scopolamine-induced memory impairment via an oxido-inflammatory mechanism and modulation of the central cholinergic system.

Beyond reconsolidation: The need for a broad theoretical approach in clinical translations of research on retrieval-induced plasticity.

Experimental findings showing that retrieved memories are labile and vulnerable to disruption have led to important theoretical ideas at a basic science level that have been applied to the clinic at a translational level. At a theoretical level, these findings suggest that retrieved memories can be modulated by behavioral or pharmacological treatments as they are reconsolidated and returned to storage. At a clinical level, these findings suggest that treatments that target reconsolidation may help dampen or even erase especially problematic memories, such as those associated with trauma. However, there are many caveats to these effects and issues that need to be considered when thinking broadly about retrieval-induced plasticity and extensions into the clinic. First, performance during a memory test often does not reflect the entirety of the animal's knowledge about a situation; asking questions in different ways may reveal the presence of a memory that was thought to be eliminated. Second, although reconsolidation and extinction are often treated as competing processes, there is abundant evidence that extinction can progress through associative and nonassociative changes in the original memory that are often described in terms of reconsolidation effects. Third, targeting a reconsolidation process as a therapeutic may not be helpful in disorders like posttraumatic stress disorder, in which traumatic experiences induce a cascade of symptoms that are self-perpetuating and may ultimately maintain themselves long after trauma. Underlying all of these challenges is the need for a rich theoretical framework focused on retrieval-induced plasticity that is informed by developments in associative learning theory. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ramping cells in the rodent medial prefrontal cortex encode time to past and future events via real Laplace transform.

In interval reproduction tasks, animals must remember the event starting the interval and anticipate the time of the planned response to terminate the interval. The interval reproduction task thus allows for studying both memory for the past and anticipation of the future. We analyzed previously published recordings from the rodent medial prefrontal cortex [J. Henke et al., eLife10, e71612 (2021)] during an interval reproduction task and identified two cell groups by modeling their temporal receptive fields using hierarchical Bayesian models. The firing in the "past cells" group peaked at the start of the interval and relaxed exponentially back to baseline. The firing in the "future cells" group increased exponentially and peaked right before the planned action at the end of the interval. Contrary to the previous assumption that timing information in the brain has one or two time scales for a given interval, we found strong evidence for a continuous distribution of the exponential rate constants for both past and future cell populations. The real Laplace transformation of time predicts exponential firing with a continuous distribution of rate constants across the population. Therefore, the firing pattern of the past cells can be identified with the Laplace transform of time since the past event while the firing pattern of the future cells can be identified with the Laplace transform of time until the planned future event.

Daidzin enhances memory and the antischizophrenia drug olanzapine's effects, possibly through the 5-HT2A and D2 receptor interaction pathways.

Schizophrenia affects identification and disturbs our thinking and motivational capacity. Long-term use of daidzin (DZN) is evident to enhance attention and memory in experimental animals. This study aimed to investigate the effect of DZN on Swiss mice. To check animals' attention, identification, thinking, and motivational ability, we performed behavioral studies using marble burying, dust removal, and trained swimming protocols. For this, a total of 36 male Swiss albino mice were randomly divided into six groups, consisting of 6 animals in each group, as follows: control (vehicle), DZN-1.25, DZN-2.5, DZN-5 mg/kg, olanzapine (OLN)-2, and a combination of DZN-1.25 with OLN-2. Additionally, in silico studies are also performed to understand the possible molecular mechanisms behind this neurological effect. Findings suggest that DZN dose-dependently and significantly (p < .05) increased marble burying and removed dust while reducing the time to reach the target point. DZN-1.25 was found to enhance OLN's effect significantly (p < .05), possibly via agonizing its activity in animals. In silico findings suggest that DZN has strong binding affinities of -10.1 and -10.4 kcal/mol against human serotonin 2 A (5-HT2A) and dopamine 2 (D2) receptors, respectively. Additionally, DZN exhibits favorable pharmacokinetic and toxicity properties. We suppose that DZN may exert its attention- and memory-enhancing abilities by interacting with 5-HT2A and D2 receptors. It may exert a synergistic antischizophrenia-like effect with the standard drug, OLN. Further studies are required to discover the exact molecular mechanism for this neurological function in animals.

[Effects of simulated gas of thermobaric bomb charge explosion on Tau protein phosphorylation and cognitive function in rats].

Objective: To explore the effect of simulated gas of thermobaric bomb charge explosion on cognitive function and the related mechanism of damage. Methods: In January 2022, thirty-two SPF rats were selected and randomly divided into control group, exposed group 1, 2 and 3 (the exposure time of the simulated gas of the explosion of the thermobaric bomb charge was 5 min, 10 min and 15 min, respectively) according to random number table method, with 8 rats in each group. The simulated gas of the explosion of the thermobaric bomb charge were CO 0.15%, CO(2) 3%, NO 0.1%, O(2) 15%, and the rest were N(2). After 30 days of exposure, water maze was used to detect the learning and memory function of rats. Golgi staining was used to observe the number distribution and morphological structure of hippocampal neurons in rats. Western blot was used to detect the expression of Tau-5, pSer262, pSer396, pThr181 and pThr231 proteins in rats. Repeated measure ANOVA was used to compare the design data of repeated measure, one-way ANOVA was used for multi-group mean comparison, and LSD method was used for pound-wise comparison. Results: There were significant differences in the results of repeated measurement ANOVA of the water maze localization navigation test (F=80.98, P<0.001), and there was an interaction between the group and the training days (F=2.16, P=0.022). There were significant differences in escape latency of rats at the 2nd, 3rd, 4th and 5th days among all groups (P<0.05). The results of spatial exploration showed that the frequency of rats crossing the platform was significantly different among all groups (F=4.49, P=0.011). The frequency of rats crossing the platform in exposed group 2 and exposed group 3 was lower than that in control group, and the frequency of rats crossing the platform in exposed group 3 was lower than that in exposed group 1 (P<0.05). With the increase of exposure time, the number of hippocampal neurons decreased, and the dendrite spine density of neurons in CA1 region decreased (P<0.05). Compared with the control group, there was no significant difference in the relative expression level of Tau-5 protein in all exposed groups (P>0.05), but the expression level of pSer262 protein was significantly increased (P<0.05). Compared with the control group, the protein expressions of pSer396, pThr181 and pThr231 in exposed group 2 and exposed group 3 were significantly increased (P<0.05) . Conclusion: The simulated gas of the explosion of the thermobaric bomb charge may contribute to the development of cognitive dysfunction by damaging hippocampal neurons with aberrant phosphorylation of Tau proteins.

The modulation of temporal predictability on attentional boost effect.

INTRODUCTION: The attentional boost effect, characterized by better memory for background scenes coinciding with a detection target than a nontarget, is believed to stem from a temporary increase in attentional capacity at the time of an acute behavior-related event occurring. Sisk and Jiang's study found that the attentional boost effect also occurs when the target's appearance was predictable. Unfortunately, the duration of the predictive interval in Sisk and Jiang's study was fixed. Since different predictive intervals had different weakening degrees to the acuteness of the target, this fixed duration hindered further investigation into the impact of different levels of predictability on the attentional boost effect. METHOD: Using the encoding-recognition paradigm and the remembering/knowing paradigm, and setting target stimuli with different predictive interval in target detection tasks, the current study aimed to explore the influence of varying the duration of the predictive interval on the attentional boost effect. RESULTS: The attentional boost effect was observed only in the short and medium predictive duration conditions, but not in the long predictive duration condition. Moreover, as the duration of the predictive interval increased, participants' memory performance on target-paired words gradually declined, while their memory performance on distractor-paired and baseline-paired words gradually improved. CONCLUSIONS: Predictability may alter the task demands, allowing participants to more effectively allocate attentional resources to the two tasks at hand.

Neural Dynamic Principles for an Intentional Embodied Agent.

How situated embodied agents may achieve goals using knowledge is the classical question of natural and artificial intelligence. How organisms achieve this with their nervous systems is a central challenge for a neural theory of embodied cognition. To structure this challenge, we borrow terms from Searle's analysis of intentionality in its two directions of fit and six psychological modes (perception, memory, belief, intention-in-action, prior intention, desire). We postulate that intentional states are instantiated by neural activation patterns that are stabilized by neural interaction. Dynamic instabilities provide the neural mechanism for initiating and terminating intentional states and are critical to organizing sequences of intentional states. Beliefs represented by networks of concept nodes are autonomously learned and activated in response to desired outcomes. The neural dynamic principles of an intentional agent are demonstrated in a toy scenario in which a robotic agent explores an environment and paints objects in desired colors based on learned color transformation rules.

Does lecture playback speed not affect memory and concentration in medical students?

Merhavy et al.'s study on the impact of lecture playback speeds on concentration and memory is valuable as it is one of the few studies on how different playback speeds may affect medical students' learning. However, despite the novelty of this study, some limitations concerning its methodological rigor, including statistical analyses, lack of evaluation of confounders, unclear characteristics of participants, and lack of a true control group, need to be considered in the interpretation of findings.

Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia.

The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 × 1011 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia.

Organizing the coactivity structure of the hippocampus from robust to flexible memory.

New memories are integrated into prior knowledge of the world. But what if consecutive memories exert opposing demands on the host brain network? We report that acquiring a robust (food-context) memory constrains the mouse hippocampus within a population activity space of highly correlated spike trains that prevents subsequent computation of a flexible (object-location) memory. This densely correlated firing structure developed over repeated mnemonic experience, gradually coupling neurons in the superficial sublayer of the CA1 stratum pyramidale to whole-population activity. Applying hippocampal theta-driven closed-loop optogenetic suppression to mitigate this neuronal recruitment during (food-context) memory formation relaxed the topological constraint on hippocampal coactivity and restored subsequent flexible (object-location) memory. These findings uncover an organizational principle for the peer-to-peer coactivity structure of the hippocampal cell population to meet memory demands.

Vitamin D Deficiency Does Not Affect Cognition and Neurogenesis in Adult C57Bl/6 Mice.

Vitamin D deficiency is a global problem. Vitamin D, the vitamin D receptor, and its enzymes are found throughout neuronal, ependymal, and glial cells in the brain and are implicated in certain processes and mechanisms in the brain. To investigate the processes affected by vitamin D deficiency in adults, we studied vitamin D deficient, control, and supplemented diets over 6 weeks in male and female C57Bl/6 mice. The effect of the vitamin D diets on proliferation in the neurogenic niches, changes in glial cells, as well as on memory, locomotion, and anxiety-like behavior, was investigated. Six weeks on a deficient diet was adequate time to reach deficiency. However, vitamin D deficiency and supplementation did not affect proliferation, neurogenesis, or astrocyte changes, and this was reflected on behavioral measures. Supplementation only affected microglia in the dentate gyrus of female mice. Indicating that vitamin D deficiency and supplementation do not affect these processes over a 6-week period.

Impact of Peptide Transport and Memory Function in the Brain.

Recent studies have reported the benefits of food-derived peptides for memory dysfunction. Beyond the physiological effects of peptides, their bioavailability to the brain still remains unclear since the blood-brain barrier (BBB) strictly controls the transportation of compounds to the brain. Here, updated transportation studies on BBB transportable peptides are introduced and evaluated using in vitro BBB models, in situ perfusion, and in vivo mouse experiments. Additionally, the mechanisms of action of brain health peptides in relation to the pathogenesis of neurodegenerative diseases, particularly Alzheimer's disease, are discussed. This discussion follows a summary of bioactive peptides with neuroprotective effects that can improve cognitive decline through various mechanisms, including anti-inflammatory, antioxidative, anti-amyloid ß aggregation, and neurotransmitter regulation.

Hunger, Satiety, and Their Vulnerabilities.

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

Transitional gradation and the distinction between episodic and semantic memory.

In this article, we explore various arguments against the traditional distinction between episodic and semantic memory based on the metaphysical phenomenon of transitional gradation. Transitional gradation occurs when two candidate kinds A and B grade into one another along a continuum according to their characteristic properties. We review two kinds of arguments-from the gradual semanticization of episodic memories as they are consolidated, and from the composition of episodic memories during storage and recall from semantic memories-that predict the proliferation of such transitional forms. We further explain why the distinction cannot be saved from the challenges of transitional gradation by appealing to distinct underlying memory structures and applying our perspective to the impasse over research into 'episodic-like' memory in non-human animals. On the whole, we recommend replacing the distinction with a dynamic life cycle of memory in which a variety of transitional forms will proliferate, and illustrate the utility of this perspective by tying together recent trends in animal episodic memory research and recommending productive future directions. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

The constructive nature of memories in insects: bumblebees as a case study.

The view that human memory is constructive implies that recollections are not necessarily an accurate reproduction of past events. An approach to study this constructive nature of memory is by examining memory errors. In this regard, conjunction errors-i.e. incorrect recollection of new stimuli integrated by components from two previously studied stimuli-have attracted important attention in human memory research. Do animals other than humans make conjunction errors? To investigate this issue, a choice task in which training was not involved was used. Bees experienced two to-be-remembered stimuli. At the test, they were presented with four stimuli: one of the original items (i.e. old), an item made by combining two features of the original items (i.e. conjunction), an item containing a previously presented feature and a new one (i.e. feature), and an item integrated solely by new features (i.e. new). Bumblebees remembered the old items. Importantly, when making memory errors, bumblebees selected conjunction and feature lures more often than new items. These results indicate that bumblebees, like humans, spontaneously make memory conjunction errors and suggest that invertebrates' memories might also be constructive in nature. I suggest that focusing on memory errors is a solid avenue to investigate episodic (like) memory in animals.This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Memory representations during slow change blindness.

Classic change blindness is the phenomenon where seemingly obvious changes that coincide with visual disruptions (such as blinks or brief blanks) go unnoticed by an attentive observer. Some early work into the causes of classic change blindness suggested that any pre-change stimulus representation is overwritten by a representation of the altered post-change stimulus, preventing change detection. However, recent work revealed that, even when observers do maintain memory representations of both the pre- and post-change stimulus states, they can still miss the change, suggesting that change blindness can also arise from a failure to compare the stored representations. Here, we studied slow change blindness, a related phenomenon that occurs even in the absence of visual disruptions when the change occurs sufficiently slowly, to determine whether it could be explained by conclusions from classic change blindness. Across three different slow change blindness experiments we found that observers who consistently failed to notice the change had access to at least two memory representations of the changing display. One representation was precise but short lived: a detailed representation of the more recent stimulus states, but fragile. The other representation lasted longer but was fairly general: stable but too coarse to differentiate the various stages of the change. These findings suggest that, although multiple representations are formed, the failure to compare hypotheses might not explain slow change blindness; even if a comparison were made, the representations would be too sparse (longer term stores) or too fragile (short-lived stores) for such comparison to inform about the change.

Memory Load Test - A Concept for Cognitive Reserve Evaluation with Auditory Perception.

<b>Introduction:</b> Auditory scene analysis refers to the system through which the auditory system distinguishes distinct auditory events and sources to create meaningful auditory information. The exact number of directly perceived auditory stimuli is unknown, studies suggest it may range from 3 to 5. This number differs among individuals, and potentially may indirectly indicate the ability to store and process the complex information, related to the memory load, which is combined with human cognitive processes.<b>Aim:</b> This study aims to further identify and quantify the number of sounds that can be perceived simultaneously in a complex auditory environment.<b>Material and methods:</b> Participants were presented with structured acoustic recordings and were asked to identify the exact number of targeted stimuli heard throughout the test. The experiment was designed to assess the auditory load and determine the maximum number of auditory stimuli that a healthy human can perceive at once.<b>Results:</b> Our study showed that on average, participants could identify up to three sounds at once with accuracy of responses declining progressively for four sounds or more.<b>Conclusions:</b> This study aimed to investigate the human capacity to detect and identify multiple sound signals simultaneously in a noisy environment. By understanding this ability, we sought to assess cognitive reserve in individuals. Our objective was to determine if auditory load could serve as a diagnostic tool for cognitive evaluation. We believe that further research will establish the validity of this approach, and we anticipate that it is only a matter of time before it becomes a viable method for assessing cognitive function.

Impaired Hippocampal Long-Term Potentiation and Memory Deficits upon Haploinsufficiency of MDGA1 Can Be Rescued by Acute Administration of D-Cycloserine.

The maintenance of proper brain function relies heavily on the balance of excitatory and inhibitory neural circuits, governed in part by synaptic adhesion molecules. Among these, MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor 1) acts as a suppressor of synapse formation by interfering with Neuroligin-mediated interactions, crucial for maintaining the excitatory-inhibitory (E/I) balance. Mdga1-/- mice exhibit selectively enhanced inhibitory synapse formation in their hippocampal pyramidal neurons, leading to impaired hippocampal long-term potentiation (LTP) and hippocampus-dependent learning and memory function; however, it has not been fully investigated yet if the reduction in MDGA1 protein levels would alter brain function. Here, we examined the behavioral and synaptic consequences of reduced MDGA1 protein levels in Mdga1+/- mice. As observed in Mdga1-/- mice, Mdga1+/- mice exhibited significant deficits in hippocampus-dependent learning and memory tasks, such as the Morris water maze and contextual fear-conditioning tests, along with a significant deficit in the long-term potentiation (LTP) in hippocampal Schaffer collateral CA1 synapses. The acute administration of D-cycloserine, a co-agonist of NMDAR (N-methyl-d-aspartate receptor), significantly ameliorated memory impairments and restored LTP deficits specifically in Mdga1+/- mice, while having no such effect on Mdga1-/- mice. These results highlight the critical role of MDGA1 in regulating inhibitory synapse formation and maintaining the E/I balance for proper cognitive function. These findings may also suggest potential therapeutic strategies targeting the E/I imbalance to alleviate cognitive deficits associated with neuropsychiatric disorders.

Leukocyte telomere length and memory circuitry and cognition in early aging: Impact of sex and menopausal status.

Telomere length (TL) is an important cellular marker of biological aging impacting the brain and heart. However, how it is related to the brain (e.g., cognitive function and neuroanatomic architecture), and how these relationships may vary by sex and reproductive status, is not well established. Here we assessed the association between leukocyte TL and memory circuitry regional brain volumes and memory performance in early midlife, in relation to sex and reproductive status. Participants (N = 198; 95 females, 103 males; ages 45-55) underwent structural MRI and neuropsychological assessments of verbal, associative, and working memory. Overall, shorter TL was associated with smaller white matter volume in the parahippocampal gyrus and dorsolateral prefrontal cortex. In males, shorter TL was associated with worse working memory performance and corresponding smaller white matter volumes in the parahippocampal gyrus, anterior cingulate cortex, and dorsolateral prefrontal cortex. In females, the impact of cellular aging was revealed over the menopausal transition. In postmenopausal females, shorter TL was associated with poor associative memory performance and smaller grey matter volume in the right hippocampus. In contrast, TL was not related to memory performance or grey and white matter volumes in any memory circuitry region in pre/perimenopausal females. Results demonstrated that shorter TL is associated with worse memory function and smaller volume in memory circuitry regions in early midlife, an association that differs by sex and reproductive status. Taken together, TL may serve as an early indicator of sex-dependent brain abnormalities in early midlife.