Memory Consolidation In Rodents Research Articles

Hippocampal responses to electrical stimulation of the major input pathways are modulated by dentate spikes.

Dentate gyrus (DG) is important for pattern separation and spatial memory, and it is thought to gate information flow to the downstream hippocampal subregions. Dentate spikes (DSs) are high-amplitude, fast, positive local-field potential events taking place in the DG during immobility and sleep, and they have been connected to memory consolidation in rodents. DSs are a result of signaling from the entorhinal cortex (EC) to the DG, and they suppress firing of pyramidal cells in the CA3 and CA1. To study the effects of DSs to signaling in the hippocampal tri-synaptic loop, we electrically stimulated the afferent fibers of the DG, CA3, and CA1 in adult male Sprague-Dawley rats at different delays from DSs. Responses to stimulation were increased in the EC-DG synapse during DSs, and the effect was amplified after theta-burst stimulation. We concluded that DSs strengthen the excitatory signal from the EC to the DG, which is reinforced by synapse potentiation and increased excitability of granule cells after theta-burst stimulation. This signal boosting may function in enhancing plastic changes in the DG-CA3 synapse. As responses in the CA3 and CA1 remained unaffected by the DS, the DS-contingent silencing of pyramidal cells seems to be a result of a decrease in excitatory input rather than a decrease in the excitability of the pyramidal cells themselves. In addition, we found that the DSs occur asynchronously in the left and right hippocampi, giving novel evidence of lateralization of the rodent hippocampus.

The developmental and experience-dependent expression of IGF-2 in mice visual cortex

The circuitry associated with the visual cortex is particularly sensitive to experiences during the early stages of life, which are collectively known as critical periods. Critical period of ocular dominance plasticity is regulated by both environmental and genetic factors. Previous studies demonstrated that IGF-1 significantly influenced the regulation of visual cortex synaptic plasticity. IGF-2 can reportedly regulate synapse formation, dendritic spine maturation, and memory consolidation in rodents. Association between IGF-2 and the regulation of visual cortex synaptic plasticity remains unclear. Here, we first aimed to elucidate the normal expression patterns of IGF-2 and its laminar expression pattern during the process of visual cortex development in mice. This confirmed that IGF-2 may influence the regulation of ocular dominance plasticity in mice. We further elucidated the role of IGF-2 in the regulation of visual cortex synaptic plasticity by examining the effect of monocular deprivation (MD) on IGF-2 expression in the visual cortex. Interestingly, we observed that MD remarkably reduced IGF-2 expression in the visual cortex. Rodents reared in an enriched environment, with enhanced sensory, motor, and social experiences, were capable of effectively accelerating the development of the visual system and could restore normal visual acuity. Although the enriched environment facilitated the restoration of normal visual acuity in the MD mice, IGF-2 expression levels in the visual cortex remained unchanged. Therefore, we considered the possibility that IGF-2 may have a different role with regard to the modulation of plasticity in the visual cortex of the mice, which we aim to study in the future.

Elucidating the role of protein synthesis in hippocampus‐dependent memory consolidation across the day and night

It is widely acknowledged that de novo protein synthesis is crucial for the formation and consolidation of long‐term memories. While the basal activity of many signaling cascades that modulate protein synthesis fluctuates in a circadian fashion, it is unclear whether the temporal dynamics of protein synthesis‐dependent memory consolidation vary depending on the time of day. More specifically, it is unclear whether protein synthesis inhibition affects hippocampus‐dependent memory consolidation in rodents differentially across the day (i.e., the inactive phase with an abundance of sleep) and night (i.e., the active phase with little sleep). To address this question, male and female C57Bl6/J mice were trained in a contextual fear conditioning task at the beginning or the end of the light phase. Animals received a single systemic injection with the protein synthesis inhibitor anisomycin or vehicle directly, 4, 8 hr, or 11.5 hr following training, and memory was assessed after 24 hr. Here, we show that protein synthesis inhibition impaired the consolidation of context–fear memories selectively when the protein synthesis inhibitor was administered at the first three time points, irrespective of timing of training. Even though the basal activity of signaling pathways regulating de novo protein synthesis may fluctuate across the 24‐hr cycle, these results suggest that the temporal dynamics of protein synthesis‐dependent memory consolidation are similar for day‐time and night‐time learning.

Ground truth construction and parameter tuning for the detection of sleep spindle timing in rodents

BackgroundThe precise detection of cortical sleep spindles is critical to basic research on memory consolidation in rodents. Previous research using automatic spindle detection algorithms often lacks systematic parameter variations and validations. New MethodWe present a method to systematically tune and validate algorithm parameters in automatic spindle detection algorithms using a moderate number of human raters. ResultsComparing a Hilbert transform-based algorithm to a ground truth constructed by six human raters, this method produced a parameter set yielding an F1 score of 0.82 at 10 ms resolution. The algorithm performance fell within the range of human agreement with the ground truth. Both human and algorithm failures arose largely from disagreement in spindle boundaries rather than spindle occurrence. With no additional tuning, the algorithm performed similarly in recordings from different days or rats. Comparison with existing methodsMost spindle detection algorithms do not perform systematic parameter variations and validation using a ground truth. To our knowledge, our study is the first in which rodent spindle data is scored by humans, and in which an automatic spindle detection algorithm is evaluated with respect to this ground truth. The rodent data from this study make it possible to compare our algorithm with others previously tested on human data. ConclusionsWe present a general ground truth based approach for the tuning and validation of spindle extraction algorithms and suggest that algorithms aimed at extracting precise spindle timing in rats should use a systematic approach for parameter tuning.

Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice

The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents.

Closed-loop transcranial alternating current stimulation of slow oscillations

Abstract Transcranial alternating current stimulation (tACS) is an emerging non-invasive tool for modulating brain oscillations. There is evidence that weak oscillatory electrical stimulation during sleep can entrain cortical slow oscillations to improve the memory consolidation in rodents and humans. Using a novel method and a custom built stimulation device, automatic stimulation of slow oscillations in-phase with the endogenous activity in a real-time closed-loop setup is possible. Preliminary data from neuroplasticity experiments show a high detection performance of the proposed method, electrical measurements demonstrate the outstanding quality of the presented stimulation device.

Hippocampal NMDA receptors and the previous experience effect on memory

N-methyl-D-aspartate receptors (NMDAR) are thought to be responsible for switching synaptic activity specific patterns into long-term changes in synaptic function and structure, which would support learning and memory. Hippocampal NMDAR blockade impairs memory consolidation in rodents, while NMDAR stimulation improves it.Adult rats that explored twice an open field (OF) before a weak though overthreshold training in inhibitory avoidance (IA), expressed IA long-term memory in spite of the hippocampal administration of MK-801, which currently leads to amnesia.Those processes would involve different NMDARs. The selective blockade of hippocampal GluN2B-containing NMDAR with ifenprodil after training promoted memory in an IA task when the training was weak, suggesting that this receptor negatively modulates consolidation.In vivo, after 1h of an OF exposure-with habituation to the environment-, there was an increase in GluN1 and GluN2A subunits in the rat hippocampus, without significant changes in GluN2B. Coincidentally, in vitro, in both rat hippocampal slices and neuron cultures there was an increase in GluN2A-NMDARs surface expression at 30min; an increase in GluN1 and GluN2A levels at about 1h after LTP induction was also shown.We hypothesize that those changes in NMDAR composition could be involved in the “anti-amnesic effect” of the previous OF. Along certain time interval, an increase in GluN1 and GluN2A would lead to an increase in synaptic NMDARs, facilitating synaptic plasticity and memory; while then, an increase in GluN2A/GluN2B ratio could protect the synapse and the already established plasticity, perhaps saving the specific trace.

Improved long-term memory via enhancing cGMP-PKG signaling requires cAMP-PKA signaling.

Memory consolidation is defined by the stabilization of a memory trace after acquisition, and consists of numerous molecular cascades that mediate synaptic plasticity. Commonly, a distinction is made between an early and a late consolidation phase, in which early refers to the first hours in which labile synaptic changes occur, whereas late consolidation relates to stable and long-lasting synaptic changes induced by de novo protein synthesis. How these phases are linked at a molecular level is not yet clear. Here we studied the interaction of the cyclic nucleotide-mediated pathways during the different phases of memory consolidation in rodents. In addition, the same pathways were studied in a model of neuronal plasticity, long-term potentiation (LTP). We demonstrated that cGMP/protein kinase G (PKG) signaling mediates early memory consolidation as well as early-phase LTP, whereas cAMP/protein kinase A (PKA) signaling mediates late consolidation and late-phase-like LTP. In addition, we show for the first time that early-phase cGMP/PKG signaling requires late-phase cAMP/PKA-signaling in both LTP and long-term memory formation.

Gender Difference in the Effect of Examination Stress on Brain Oscillations during Memory Tasks

Background: Researches revealed that increased levels of stress hormones lead to enhancement of memory consolidation in rodents. Recently, it became apparent that the brain oscillations reflect cognitive aspects and information processing in the brain. Quantitative electroencephalogram (qEEG) provides an objective assessment of the electrical activity of the brain via many techniques such as power spectral analysis and coherence. Aim: To assess the effect of gender on the qEEG oscillations during the delayed memory retrieval after exposure to acute stress. Subjects and Methods: This prospective (longitudinal) study was applied on 34 healthy undergraduate medical students from both genders (17 males and 17 females) in the Faculty of Medicine, Suez Canal University. The qEEG analysis was done in neurology department, Suez Canal University Hospital using the relative power (RP) during memory tasks. Serum cortisol was analyzed by enzyme linked immunosorbent assay (ELISA) as a measure for stress. Results: The results revealed insignificant effect of gender on the quantitative analysis of EEG oscillations regarding the mean relative power in all frequency bands (delta δ: 2.36±0.72; 2.04±0.46, theta Ɵ: 13.72±3.13; 12.72±3.58, alpha α: 12.72±3.58; 18.50±3.81 and beta β: 33.26±3.23; 32.72±4.47 for males and females respectively during the examination period). Whereas, there was a positive correlation between the serum cortisol level and the mean relative power of delta (r: 0.53, p=0.03), and theta (r: 0.55, p=0.02) and a negative correlation with beta (r: -0.51, p=0.04) bands in males only. Conclusion: There are positive correlations for delta and theta bands and negative correlation for beta band between the quantitative electroencephalographic analysis (RP) with the hormonal measure of the stress in spite of the insignificant changes in the EEG oscillations in the non-stress and stress periods.

Simvastatin treatment highlights a new role for the isoprenoid/cholesterol biosynthetic pathway in the modulation of emotional reactivity and cognitive performance in rats.

The aim of the present work was to shed light on the role played by the isoprenoid/cholesterol biosynthetic pathway in the modulation of emotional reactivity and memory consolidation in rodents through the inhibition of the key and rate-limiting enzyme 3-hydroxy 3-methylglutaryl Coenzyme A reductase (HMGR) both in vivo and in vitro with simvastatin. Three-month-old male Wistar rats treated for 21 days with simvastatin or vehicle were tested in the social interaction, elevated plus-maze, and inhibitory avoidance tasks; after behavioral testing, the amygdala, hippocampus, prefrontal cortex, dorsal, and ventral striatum were dissected out for biochemical assays. In order to delve deeper into the molecular mechanisms underlying the observed effects, primary rat hippocampal neurons were used. Our results show that HMGR inhibition by simvastatin induces anxiogenic-like effects in the social interaction but not in the elevated plus-maze test, and improves memory consolidation in the inhibitory avoidance task. These effects are accompanied by imbalances in the activity of specific prenylated proteins, Rab3 and RhoA, involved in neurotransmitter release, and synaptic plasticity, respectively. Taken together, the present findings indicate that the isoprenoid/cholesterol biosynthetic pathway is critically involved in the physiological modulation of both emotional and cognitive processes in rodents.

Dopamine boosts ageing memories

Dopamine release in the hippocampus has been shown to be essential for memory consolidation in rodents. Similarly, Chowdhury et al. now demonstrate that, in humans, the persistence of episodic memory is enhanced following pharmacological increase in hippocampal dopamine.

Sleep selectively enhances hippocampus-dependent memory in mice.

Sleep has been implicated as playing a critical role in memory consolidation. Emerging evidence suggests that reactivation of memories during sleep may facilitate the transfer of declarative memories from the hippocampus to the neocortex. Previous rodent studies have utilized sleep-deprivation to examine the role of sleep in memory consolidation. The present study uses a novel, naturalistic paradigm to study the effect of a sleep phase on rodent Pavlovian fear conditioning, a task with both hippocampus-dependent and -independent components (contextual vs. cued memories). Mice were trained 1 hour before their sleep/rest phase or awake/active phase and then tested for contextual and cued fear 12 or 24 hr later. The authors found that hippocampus-dependent contextual memory was enhanced if tested after a sleep phase within 24 hr of training. This enhancement was specific to context, not cued, memory. These findings provide direct evidence of a role for sleep in enhancing hippocampus-dependent memory consolidation in rodents and detail a novel paradigm for examining sleep-induced memory effects.