Behavioural Memory Test Research Articles

Temporal Dynamics of Competition between Statistical Learning and Episodic Memory in Intracranial Recordings of Human Visual Cortex.

The function of long-term memory is not just to reminisce about the past, but also to make predictions that help us behave appropriately and efficiently in the future. This predictive function of memory provides a new perspective on the classic question from memory research of why we remember some things but not others. If prediction is a key outcome of memory, then the extent to which an item generates a prediction signifies that this information already exists in memory and need not be encoded. We tested this principle using human intracranial EEG as a time-resolved method to quantify prediction in visual cortex during a statistical learning task and link the strength of these predictions to subsequent episodic memory behavior. Epilepsy patients of both sexes viewed rapid streams of scenes, some of which contained regularities that allowed the category of the next scene to be predicted. We verified that statistical learning occurred using neural frequency tagging and measured category prediction with multivariate pattern analysis. Although neural prediction was robust overall, this was driven entirely by predictive items that were subsequently forgotten. Such interference provides a mechanism by which prediction can regulate memory formation to prioritize encoding of information that could help learn new predictive relationships.SIGNIFICANCE STATEMENT When faced with a new experience, we are rarely at a loss for what to do. Rather, because many aspects of the world are stable over time, we rely on past experiences to generate expectations that guide behavior. Here we show that these expectations during a new experience come at the expense of memory for that experience. From intracranial recordings of visual cortex, we decoded what humans expected to see next in a series of photographs based on patterns of neural activity. Photographs that generated strong neural expectations were more likely to be forgotten in a later behavioral memory test. Prioritizing the storage of experiences that currently lead to weak expectations could help improve these expectations in future encounters.

Amelioration of Scopolamine-Induced Cognitive Dysfunction in Experimental Mice Using the Medicinal Plant Salvia moorcroftiana.

Salvia moorcroftiana is medicinally used in various parts of the world to treat a number of diseases. In the literature, the antiamnesic activity of this plant has not yet been reported. Therefore, the current study was aimed at evaluating the in vivo antiamnesic (scopolamine-induced) potential of Salvia moorcroftiana. The major phytochemical groups such as total phenolic (TPC), total tannin (TTC), and total flavonoid content (TFC) in methanolic extract (SlMo-Crd) and subsequent fractions of Salvia moorcroftiana were quantified using standard methods. The in vitro anticholinesterase (against butyryl cholinesterase; BChE and acetylcholinesterase; AChE) and antioxidant (against 2,2-diphenyl-1-picrylhydrazyl; DPPH and 2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid); ABTS free radicals) potentials of crude (SIMO-Crd) extract and fractions (hexane; SlMo-Hex, chloroform; SlMo-Chl, ethyl acetate; SlMo-Et) were also determined. The SlMo-Crd at doses of 100 and 200 mg/kg body weight compared to fractions of 75 and 150 mg/kg body weight (which were 1/10th of the highest dose tested in acute toxicity tests) were evaluated for their memory enhancement and learning behavior in normal and scopolamine-induced mental dysfunction in mice using behavioral memory tests such as the Y-maze test and novel object recognition test (NORT). Moreover, the samples were further evaluated for acetylcholine contents and biochemical markers such as MDA (malondialdehyde), SOD (superoxide dismutase), CAT (catalase), and GSH (glutathione peroxidase) levels. The maximum TPC with a value of 114.81 ± 1.15 mg GAE/g, TTC with a value of 106.79 ± 1.07 mg GAE/g, and TFC with a value of 194.29 ± 0.83 mg RE/g were recorded for the SlMo-Chl fraction. Against the DPPH free radical, the methanolic extract exhibited an IC50 value of 95.29 ± 1.06 µg/mL whereas, among the fractions, the best activity was observed for the SlMo-Chl fraction with an IC50 of 75.02 ± 0.91 µg/mL, followed by SlMoS-Et with an IC50 value of 88.71 ± 0.87 µg/mL. Among the extracts, the SlMo-Chl and SlMo-Et fractions inverted the amnesic effects of scopolamine in mice effectively. Additionally, the SlMo-Chl and SIMO-Et fractions considerably enhanced the percent spontaneous alteration performance in the Y-maze test with values of 65.18 ± 2.61/69.51 ± 2.71 and 54.92 ± 2.49/60.41 ± 2.69, respectively, for the tested doses. The discrimination index (DI) in experimental mice was considerably enhanced by the SlMo-Chl in the NORT with values of 59.81 ± 1.21/61.22 ± 1.31% DI correspondingly for the tested doses, as mentioned above, followed by the SlMo-Et extract. The selected plant in the form of extracts ameliorated the effects of amnesia in mice and could, therefore, be used as a therapy for amnesia; however, this is subject to further exploration in other animal models and the isolation of the responsible compounds.

Lacidipine Attenuates Symptoms of Nicotine Withdrawal in Mice.

Nicotine-withdrawal after daily exposure manifests somatic and affective symptom including a range of cognitive deficits. Earlier studies suggested participation of L-type calcium channels (LTCCs) in development of nicotine dependence and expression of withdrawal signs. An upsurge in Ca2+-induced oxidative stress in brain underlies the biochemical events and behavioral signs of nicotine-withdrawal. The present study is aimed to explore the effects of lacidipine (LTCC antagonist) against nicotine-withdrawal. Swiss albino mice were administered ( -)-nicotine hydrogen tartrate (3.35mg/kg, t.i.d.) from days 1 to 7 and alongside lacidipine (0.3, 1, and 3mg/kg, i.p.) given from days 1 to 14. Somatic withdrawal signs were noted 48h after last dose of nicotine. Bay-K8644 (LTCC agonist) was administered in mice subjected to nicotine-withdrawal and lacidipine (3mg/kg) treatments. Behavioral tests of memory, anxiety, and depression were conducted on days 13 and 14 to assess the effects of lacidipine on affective symptoms of nicotine-withdrawal. Biomarkers of oxido-nitrosative were quantified in the whole brain. Nicotine-withdrawal significantly enhanced somatic signs and symptoms of anxiety, depression, and memory impairment in mice. Lacidipine (1 and 3mg/kg) attenuated nicotine-withdrawal induced somatic symptoms and also ameliorated behavioral abnormalities. Nicotine-withdrawal triggered an upsurge in brain lipid peroxidation, total nitrite content, and decline in antioxidants, and these effects were attenuated by lacidipine. Bay-K8644 significantly abolished improvement in somatic and affective symptoms, and antioxidant effects by lacidipine in mice subjected to nicotine-withdrawal. Lacidipine mitigated nicotine-withdrawal triggered somatic and affective symptoms owing to decrease in brain oxido-nitrosative stress.

Differential Involvement of Kinase Activity of Ca2+/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse.

Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) is a key mediator of activity-dependent neuronal modifications and has been implicated in the molecular mechanisms of learning and memory. Indeed, several types of CaMKIIα knock-in (KI) and knock-out (KO) mice revealed impairments in hippocampal synaptic plasticity and behavioral learning. On the other hand, a similar role for CaMKIIα has been implicated in amygdala-dependent memory, but detailed analyses have not much been performed yet. To better understand its involvement in amygdala-dependent memory as compared to hippocampus-dependent memory, here we performed biochemical analyses and behavioral memory tests using the kinase-dead CaMKIIα (K42R)-KI mouse. In the Morris water maze tasks, homozygous mutants performed well in the visible platform trials, while they failed to form spatial memory in the hippocampus-dependent hidden platform trials. In fear conditioning, these mice were impaired but showed a certain level of amygdala-dependent cued fear memory, which lasted four weeks, while they showed virtually no hippocampus-dependent context discrimination. Neither stronger stimulation nor repetitive stimulation compensated for their memory deficits. The differential outcome of hippocampus- and amygdala-dependent memory in the mutant mouse was not due to differential expression of CaMKIIα between the hippocampus and the amygdala, because biochemical analyses revealed that both kinase activity and protein levels of CaMKII were indistinguishable between the two brain regions. These results indicate that kinase activity of CaMKIIα is indispensable for hippocampus-dependent memory, but not necessarily for amygdala-dependent memory. There may be a secondary, CaMKIIα activity-independent pathway, in addition to the CaMKIIα activity-dependent pathway, in the acquisition of amygdala-dependent memory.

Electroacupuncture ameliorates memory impairments by enhancing oligodendrocyte regeneration in a mouse model of prolonged cerebral hypoperfusion

We modeled prolonged cerebral hypoperfusion in mice using bilateral common carotid artery stenosis (BCAS) and electroacupuncture (EA) stimulation was applied at two acupoints, Baihui (GV20) and Dazhui (GV14). In behavioral tests of memory, BCAS produced impairments in spatial and short-term memory in mice that were attenuated by therapeutic EA stimulation. Therapeutic use of EA in BCAS also enhanced oligodendrocyte (OL) differentiation from oligodendrocyte precursor cells (OPCs), in association with white matter improvements in the corpus callosum (CC). In PCR analyses of growth factor gene expression, significant positive changes in 3 genes were observed following EA stimulation in BCAS, and here we highlight alterations in neurotrophin-4/5 (NT4/5). We confirmed EA-mediated positive changes in the expression of NT4/5 and its receptor, tyrosine receptor kinase B (TrkB). Treatment of naïve and BCAS + EA animals with a selective TrkB antagonist, ANA-12, produced losses of myelin and cognitive function that were ameliorated by EA therapy. Moreover, following BCAS we observed an EA-dependent increase in phospho-activated CREB (a downstream mediator of NT4/5-TrkB signaling) in OPCs and OLs of the CC. Our results suggest that EA stimulation promotes the recovery of memory function following white matter injury via a mechanism that promotes oligodendrocyte regeneration and involves NT4/5-TrkB signaling.

Developmental Dyslexia With and Without Language Impairment: ERPs Reveal Qualitative Differences in Morphosyntactic Processing

This study aimed to characterize neuropsychological and linguistic skills in children with Developmental Dyslexia (DD) with and without Language Impairment (LI). Behavioral tests of short-term memory, phonemic awareness, and morphosyntactic processing and electrophysiological responses to agreement violations were administered to 32 DD children (16 with additional LI) and 16 controls. Behavioral data revealed quantitative differences among groups: DD+LI children showed the worst performance, followed by DD-only children and controls. Event-related potential results confirmed atypical morphosyntactic processing in the DD-only group, highlighting qualitative differences between groups. These results support multifactor models of learning disabilities, where different patterns of deficits characterize different subgroups.

Learning and Working Memory In Mice Under Different Lighting Conditions

Objective. This study aimed to investigate the effect of different light/ dark cycles and light intensity during behavioral tests of learning and working memory in Swiss mice. Method. Fifty-seven Swiss mice were kept in a housing room in either a 12:12h light/dark cycle (LD), constant light (LL), or constant darkness (DD). The animals were then tested in Lashley maze and Object recognition task under either 500 or 0 lux illumination, resulting in six treatments (LD-500, LD-0, LL500, LL-0, DD-500, and DD-0). Results. There were no significant differences between the conditions of light/dark, or between tests at 500 and 0 lux. Animals kept in constant darkness and tested at 0 lux (DD-0) had learning and working memory impaired, as demonstrated by slower learning in Lashley III maze, and no object recognition in Object recognition task. Conclusion. Continuous darkness throughout the experiment affected the learning and working memory of Swiss mice.

Learning and Working Memory In Mice Under Different Lighting Conditions

Objective. This study aimed to investigate the effect of different light/ dark cycles and light intensity during behavioral tests of learning and working memory in Swiss mice. Method. Fifty-seven Swiss mice were kept in a housing room in either a 12:12h light/dark cycle (LD), con­stant light (LL), or constant darkness (DD). The animals were then tested in Lashley maze and Object recognition task under either 500 or 0 lux illumination, resulting in six treatments (LD-500, LD-0, LL- 500, LL-0, DD-500, and DD-0). Results. There were no significant differences between the conditions of light/dark, or between tests at 500 and 0 lux. Animals kept in constant darkness and tested at 0 lux (DD-0) had learning and working memory impaired, as demon­strated by slower learning in Lashley III maze, and no object recogni­tion in Object recognition task. Conclusion. Continuous darkness throughout the experiment affected the learning and working mem­ory of Swiss mice.

Behavioral analysis of relaxin-3 deficient mice.

Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus of the pons, projecting axons to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. We generated relaxin-3 gene knockout (KO) mice and examined them using a battery of behavioral tests of sensory/motor functions and emotion-related behaviors. Relaxin-3 KO mice exhibited normal growth and appearance. There was no difference in bodyweight among genotypes in both normal and high fat diet feeding. In addition, there were no significant differences between wild-type and KO mice in social interaction, depression-like behavior, and short memory test. However, in the elevated plus maze test, KO mice exhibited a robust increase in the tendency to enter open arms, although they exhibited normal performance in a light/dark transition test and showed no difference from wild-type mice in the open field test. Taken together, these results indicate that relaxin-3 KO mice exhibit mild anxiolytic characteristics relative to wild-type mice, suggesting that this peptide is involved in anxiety-related behavior.

NF-κB p50 subunit knockout impairs late LTP and alters long term memory in the mouse hippocampus

BackgroundNuclear factor kappa B (NF-κB) is a transcription factor typically expressed with two specific subunits (p50, p65). Investigators have reported that NF-κB is activated during the induction of in vitro long term potentiation (LTP), a paradigm of synaptic plasticity and correlate of memory, suggesting that NF-κB may be necessary for some aspects of memory encoding. Furthermore, NF-κB has been implicated as a potential requirement in behavioral tests of memory. Unfortunately, very little work has been done to explore the effects of deleting specific NF-κB subunits on memory. Studies have shown that NF-κB p50 subunit deletion (p50−/−) leads to memory deficits, however some recent studies suggest the contrary where p50−/− mice show enhanced memory in the Morris water maze (MWM). To more critically explore the role of the NF-κB p50 subunit in synaptic plasticity and memory, we assessed long term spatial memory in vivo using the MWM, and synaptic plasticity in vitro utilizing high frequency stimuli capable of eliciting LTP in slices from the hippocampus of NF-κB p50−/− versus their controls (p50+/+).ResultsWe found that the lack of the NF-κB p50 subunit led to significant decreases in late LTP and in selective but significant alterations in MWM tests (i.e., some improvements during acquisition, but deficits during retention).ConclusionsThese results support the hypothesis that the NF-κ p50 subunit is required in long term spatial memory in the hippocampus.

Evidence for the involvement of calbindin D28k in the presenilin 1 model of Alzheimer's disease

Pathological hallmarks of Alzheimer's disease include memory deficits, accumulation of amyloid beta (Aβ) plaques, the appearance of neurofibrillary tangles, and dysregulation of calcium homeostasis, which has been linked to mutations in the presenilin gene that code for presenilin (PS) proteins. PSs are a family of multi-pass transmembrane proteins where normal presenilins (PS1 and PS2) are highly localized in the endoplasmic reticulum (ER). Several past studies have explored alterations in long-term potentiation (LTP), a proposed molecular correlate of memory, and in behavioral tests of spatial memory in a variety of PS1 models. These reports suggest that calcium plays a role in these alterations, but mechanistic explanations for changes in LTP and in behavioral tests of memory are still lacking. To test the hypothesis that calcium-related mechanisms, such as changes in calcium buffering, are associated with alterations in LTP and memory, we utilized in vitro experimental paradigms of LTP in hippocampal slices obtained from the PS1-M146V transgenic mouse model of Alzheimer's disease (AD). We also used the in vivo Morris water maze (MWM), a test for hippocampal dependent spatial memory. In addition, we used cellular assays to explore molecular mechanisms. We confirm that PS1 mutations (M146V) enhance LTP. We also find increases in some parameters of the MWM, and alterations in other parameters, such as path length indicating impairment in cognitive functioning in PS1-M146V mice. In addition, these findings are observed in association with increased calbindin D28K expression in the CA1 hippocampus of PS1-M146V mice.

An evaluation of the effectiveness of group therapy for memory problems

To investigate the effectiveness of group treatment for memory problems. A cross-over design was employed to compare the memory improvement of subjects while attending a weekly memory therapy session with a waiting period. Outpatients. A variety of memory strategies were taught, and practical advice was provided in the use of external aids. No improvement in memory function was detected on the Behavioural Memory Test or Subjective Memory Questionnaire. There was an increase in the number of memory aids reported as being used after attending the group (p less than 0.05). The number of items reported on the Subjective Memory Questionnaire as 'bothering' the patient decreased in frequency (p less than 0.05) after group treatment. Attendance at a memory group increased the use of memory aids but did not affect memory impairment.