Short-term Memory Formation Research Articles

Long-term memory in <i>Thrips tabaci</i> (Thysanoptera, Thripidae)

Microinsects are capable of associative learning and memory retention despite significant reduction in the number and size of neurons. Previously, the capabilities of Thrips tabaci (Thysanoptera, Thripidae) for associative learning and the formation of short-term memory have been demonstrated. In this study, an additional training session was added, as well as a time interval between them. Increasing the number of training sessions and spacing these out over time allowed us to demonstrate the persistence of memory traces for up to 24 hours. Thus, for the first time, the presence of consolidated forms of memory in the order Thysanoptera has been revealed.

Distinct effects of slow and fast theta tACS in enhancing temporal memory

Abstract Temporal memory plays a crucial role in organizing real-life events into meaningful segments. Previous research suggests that the clustering of temporally related information builds on the neural correlates of associative memory, including theta oscillations. Transcranial alternating current stimulation (tACS) provides a means of modulating theta oscillations within associative memory networks, possibly including hippocampal modulation when targeting parietal cortex. Theta oscillations are not limited to a single frequency range, but instead, exhibit functional specialization, with slow theta (3 Hz) implicated in short-term episodic memory formation and fast theta (8 Hz) involved in spatial navigation. This study aimed to investigate the distinct effects of slow and fast theta stimulation on temporal memory. Participants encoded visual objects paired with frame color while receiving tACS stimulation at 8 Hz, 3 Hz, or sham targeting the left parietal cortex. The frame color would change for every eight objects, establishing a context boundary with each color change. Subsequently, participants performed a timeline task to assess temporal memory performance. Results showed that slow, but not fast, theta stimulation led to an enhancement in temporal accuracy (absolute temporal error) compared to sham tACS, in support of our main hypothesis. Under sham stimulation, participants consistently underestimated the temporal position of items presented further away from boundary, compared to those presented at boundary. This finding resembled temporal compression observed during event segmentation. Interestingly, fast, but not slow, theta stimulation reduced this temporal bias (rated position— actual position). This study represents the first tACS evidence for differential contributions of slow versus fast theta to temporal memory formation in humans. We speculate that parietal theta tACS may modulate the hippocampus and facilitate temporal memory formation.

Erlotinib regulates short-term memory, tau/Aβ pathology, and astrogliosis in mouse models of AD.

Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor that is approved by the FDA to treat non-small cell lung cancer (NSCLC). Several membrane receptors, including EGFR, interact with amyloid β (Aβ), raising the possibility that erlotinib could have therapeutic effects on Alzheimer's disease (AD). However, the effects of erlotinib on Aβ/tau-related pathology and cognitive function in mouse models of AD and its mechanisms of action have not been examined in detail. To investigate the effects of erlotinib on cognitive function and AD pathology, 3 to 6-month-old PS19 mice and 3 to 3.5-month-old 5xFAD mice and WT mice were injected with vehicle (5% DMSO + 10% PEG + 20% Tween80 + 65% D.W.) or erlotinib (20 mg/kg, i.p.) daily for 14 or 21 days. Then, behavioral tests, Golgi staining, immunofluorescence staining, western blotting ELISA, and real-time PCR were conducted. We found that erlotinib significantly enhanced short-term spatial memory and dendritic spine formation in 6-month-old P301S tau transgenic (PS19) mice. Importantly, erlotinib administration reduced tau phosphorylation at Ser202/Thr205 (AT8) and Thr231 (AT180) and further aggregation of tau into paired helical fragments (PHFs) and neurofibrillary tangles (NFTs) in 3-month-old and/or 6-month-old PS19 mice by suppressing the expression of the tau kinase DYRK1A. Moreover, erlotinib treatment decreased astrogliosis in 6-month-old PS19 mice and reduced proinflammatory responses in primary astrocytes (PACs) from PS19 mice. In 3- to 3.5-month-old 5xFAD mice, erlotinib treatment improved short-term spatial memory and hippocampal dendritic spine number and diminished Aβ plaque deposition and tau hyperphosphorylation. Furthermore, erlotinib-treated 5xFAD mice exhibited significant downregulation of astrocyte activation, and treating PACs from 5xFAD mice with erlotinib markedly reduced cxcl10 (reactive astrocyte marker) and gbp2 (A1 astrocyte marker) mRNA levels and proinflammatory cytokine mRNA and protein levels. Taken together, our results suggest that erlotinib regulates tau/Aβ-induced AD pathology, cognitive function, and Aβ/tau-evoked astrogliosis and therefore could be a potent therapeutic drug for ameliorating AD symptoms.

Novel role of NCoR1 in impairing spatial memory through the mediation of a novel interacting protein DEC2

Long-term memory formation requires de novo RNA and protein synthesis. Using differential display PCR, we found that the NCoR1 cDNA fragment is differentially expressed between fast learners and slow learners, with fast learners showing a lower expression level than slow learners in the water maze learning task. Fast learners also show lower NCoR1 mRNA and protein expression levels. In addition, spatial training decreases both NCoR1 mRNA and protein expression, whereas NCoR1 conditional knockout (cKO) mice show enhanced spatial memory. In studying the molecular mechanism, we found that spatial training decreases the association between NCoR1 and DEC2. Both NCoR1 and DEC2 suppress the expression of BDNF, integrin α3 and SGK1 through C/EBPα binding to their DNA promoters, but overexpression of DEC2 in NCoR1 cKO mice rescues the decreased expression of these proteins compared with NCoR1 loxP mice overexpressing DEC2. Further, spatial training decreases DEC2 expression. Spatial training also enhances C/EBPα binding to Bdnf, Itga3 and Sgk1 promoters, an effect also observed in fast learners, and both NCoR1 and DEC2 control C/EBPα activity. Whereas knockdown of BDNF, integrin α3 or SGK1 expression impairs spatial learning and memory, it does not affect Y-maze performance, suggesting that BDNF, integrin α3 and SGK1 are involved in long-term memory formation, but not short-term memory formation. Moreover, NCoR1 expression is regulated by the JNK/c-Jun signaling pathway. Collectively, our findings identify DEC2 as a novel interacting protein of NCoR1 and elucidate the novel roles and mechanisms of NCoR1 and DEC2 in negative regulation of spatial memory formation.

Roles of feedback and feed-forward networks of dopamine subsystems: insights from Drosophila studies.

Across animal species, dopamine-operated memory systems comprise anatomically segregated, functionally diverse subsystems. Although individual subsystems could operate independently to support distinct types of memory, the logical interplay between subsystems is expected to enable more complex memory processing by allowing existing memory to influence future learning. Recent comprehensive ultrastructural analysis of the Drosophila mushroom body revealed intricate networks interconnecting the dopamine subsystems-the mushroom body compartments. Here, we review the functions of some of these connections that are beginning to be understood. Memory consolidation is mediated by two different forms of network: A recurrent feedback loop within a compartment maintains sustained dopamine activity required for consolidation, whereas feed-forward connections across compartments allow short-term memory formation in one compartment to open the gate for long-term memory formation in another compartment. Extinction and reversal of aversive memory rely on a similar feed-forward circuit motif that signals omission of punishment as a reward, which triggers plasticity that counteracts the original aversive memory trace. Finally, indirect feed-forward connections from a long-term memory compartment to short-term memory compartments mediate higher-order conditioning. Collectively, these emerging studies indicate that feedback control and hierarchical connectivity allow the dopamine subsystems to work cooperatively to support diverse and complex forms of learning.

PHYSICAL EUSTRESSORS AS POTENTIAL TOOLS TO IMPROVE CROP STRESS TOLERANCE (REVIEW)

Background. The processes occurring in plants and their seeds under stress, as well as the defense mechanisms used by plants under stress, are poorly understood, which makes it impossible to use them to increase yields.
 Purpose. Review and analysis of scientific publications, devoted to the phenomenon of stress memory acquired by plants as a result of physical stressors on their seeds and possible applications of this phenomenon in plant growing and crop breeding.
 Materials and methods. A selection and systematic review of scientific articles on the research topic for the period 2016-2023 was performed. The study consisted of the following steps: research literature search, evaluation and selection, data synthesis and analysis.
 Results. The use of hormetic effects of physical agents to stimulate seed germination of crops is effective. Responses to abiotic stresses could be 'trained' by priming so that the plant becomes better able to cope with later stress. Evidence of short-term and transgenerational memory formation following plant priming has been obtained. An epigenetic mechanism for the formation of long-term stress memory in plants as a result of a physical eustressor has been identified. The eustressor induces specific epigenetic marks associated with environmental adaptation, forming a new stress-resistant plant phenotype. Physical eustressors have the potential to impart stress tolerance to crops to enhance phenotypic characteristics to prevent yield losses.
 Conclusion. Seed treatment with physical stressors builds plant tolerance and memory to abiotic stresses, but scientific evidence on this issue is incomplete and sketchy. The understanding and application of stress memory for breeding purposes is currently limited, but it has great potential for the development of new crop varieties.

Cofilin overactivation improves hippocampus-dependent short-term memory.

Many living organisms of the animal kingdom have the fundamental ability to form and retrieve memories. Most information is initially stored as short-term memory, which is then converted to a more stable long-term memory through a process called memory consolidation. At the neuronal level, synaptic plasticity is crucial for memory storage. It includes the formation of new spines, as well as the modification of existing spines, thereby tuning and shaping synaptic efficacy. Cofilin critically contributes to memory processes as upon activation, it regulates the shape of dendritic spines by targeting actin filaments. We previously found that prolonged activation of cofilin in hippocampal neurons attenuated the formation of long-term object-location memories. Because the modification of spine shape and structure is also essential for short-term memory formation, we determined whether overactivation of hippocampal cofilin also influences the formation of short-term memories. To this end, mice were either injected with an adeno-associated virus expressing catalytically active cofilin, or an eGFP control, in the hippocampus. We show for the first time that cofilin overactivation improves short-term memory formation in the object-location memory task, without affecting anxiety-like behavior. Surprisingly, we found no effect of cofilin overactivation on AMPA receptor expression levels. Altogether, while cofilin overactivation might negatively impact the formation of long-lasting memories, it may benefit short-term plasticity.

Social memory in female mice is rapidly modulated by 17β-estradiol through ERK and Akt modulation of synapse formation

Social memory is essential to the functioning of a social animal within a group. Estrogens can affect social memory too quickly for classical genomic mechanisms. Previously, 17β-estradiol (E2) rapidly facilitated short-term social memory and increased nascent synapse formation, these synapses being potentiated following neuronal activity. However, what mechanisms underlie and coordinate the rapid facilitation of social memory and synaptogenesis are unclear. Here, the necessity of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) signaling for rapid facilitation of short-term social memory and synaptogenesis was tested. Mice performed a short-term social memory task or were used as task-naïve controls. ERK and PI3K pathway inhibitors were infused intradorsal hippocampally 5 min before E2 infusion. Forty minutes following intrahippocampal E2 or vehicle administration, tissues were collected for quantification of glutamatergic synapse number in the CA1. Dorsal hippocampal E2 rapid facilitation of short-term social memory depended upon ERK and PI3K pathways. E2 increased glutamatergic synapse number (bassoon puncta positive for GluA1) in task-performing mice but decreased synapse number in task-naïve mice. Critically, ERK signaling was required for synapse formation/elimination in task-performing and task-naïve mice, whereas PI3K inhibition blocked synapse formation only in task-performing mice. While ERK and PI3K are both required for E2 facilitation of short-term social memory and synapse formation, only ERK is required for synapse elimination. This demonstrates previously unknown, bidirectional, rapid actions of E2 on brain and behavior and underscores the importance of estrogen signaling in the brain to social behavior.

Impact of Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Escherichia coli Oral Infusions on Cognitive Memory Decline in Mild Cognitive Impairment

Synaptic plasticity is a result of changes in the neuronal circuits which may result in the formation of protein-dependent (long-term memory (LTM) formation) and protein-independent (short-term memory (STM) formation) memories. This STM formation is based on existing proteins, but LTM formation depends on RNA and protein synthesis within the neuronal cells. This RNA and protein synthesis may depend on stimulus exposure like odour, taste, and other environmental stimuli. The present study is aimed to show the impact of oral bacterial infusions on cognitive memory formation through pre and post-infusive behavioural analysis. The results of the study revealed that oral infusions of Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and Escherichia coli result in impaired cognitive learning and memory formation. This impaired cognitive memory formation is shown with the help of two-step (pre and post-infusive) behavioural analysis. Pre-infusive behavioural study shows no decline in cognitive learning and memory formation before oral microbial infusions in a serene habituated environment. After oral microbial infusions, a post-infusive behavioural analysis may reveal a memory decline in the treated group. Comparative two-step behavioural analysis indicates that P. aeruginosa infusions strongly impact cognitive memory decline compared to the other three groups. This cognitive memory decline may happen due to the production of primary/secondary metabolites within the animal gut and their transportation to the CNS through the blood-brain barrier. The outcome of the present study states that poor oral hygiene plays a significant role in cognitive memory decline concerning mild cognitive impairment (MCI).

Glial modulation of the parallel memory formation.

Actions from glial cells could affect the readiness and efficacy of learning and memory. Using a mouse cerebellar-dependent horizontal optokinetic response motor learning paradigm, short-term memory (STM) formation during the online training period and long-term memory (LTM) formation during the offline rest period were studied. A large variability of online and offline learning efficacies was found. The early bloomers with booming STM often had a suppressed LTM formation and late bloomers with no apparent acute training effect often exhibited boosted offline learning performance. Anion channels containing LRRC8A are known to release glutamate. Conditional knockout of LRRC8A specifically in astrocytes including cerebellar Bergmann glia resulted in a complete loss of STM formation while the LTM formation during the rest period remained. Optogenetic manipulation of glial activity by channelrhodopsin-2 or archaerhodopsin-T (ArchT) during the online training resulted in enhancement or suppression of STM formation, respectively. STM and LTM are likely to be triggered simultaneously during online training, but LTM is expressed later during the offline period. STM appears to be volatile and the achievement during the online training is not handed over to LTM. In addition, we found that glial ArchT photoactivation during the rest period resulted in the augmentation of LTM formation. These data suggest that STM formation and LTM formation are parallel separate processes. Strategies to weigh more on the STM or the LTM could depend on the actions of the glial cells.

Turing instability mechanism of short-memory formation in multilayer FitzHugh-Nagumo network.

The study of brain function has been favored by scientists, but the mechanism of short-term memory formation has yet to be precise. Since the formation of short-term memories depends on neuronal activity, we try to explain the mechanism from the neuron level in this paper. Due to the modular structures of the brain, we analyze the pattern properties of the FitzHugh-Nagumo model (FHN) on a multilayer network (coupled by a random network). The conditions of short-term memory formation in the multilayer FHN model are obtained. Then the time delay is introduced to more closely match patterns of brain activity. The properties of periodic solutions are obtained by the central manifold theorem. When the diffusion coeffcient, noise intensity np, and network connection probability p reach a specific range, the brain forms a relatively vague memory. It is found that network and time delay can induce complex cluster dynamics. And the synchrony increases with the increase of p. That is, short-term memory becomes clearer.

Structure of the shaker Kv channel in low K and mechanism of slow C-type inactivation.

Voltage-activated potassium (Kv) channels open upon membrane depolarization and proceed to spontaneously inactivate. Inactivation controls neuronal firing and serves as a form of short-term memory and is implicated in various human neurological disorders. Inactivation can proceed through two distinct mechanisms: a fast ball-and-chain mechanism that blocks the inner pore, and a slower C-type mechanism that disables the ion selectivity filter. In our previous study, we determined the structures of the Shaker Kv channel and the C-type inactivated W434F mutant in 150 mM KCl condition. The Shaker Kv channel exhibits an open internal pore and the selectivity filter within the external pore in a conducting state. By contrast, the W434F mutant exhibits a 4 Å dilation of the external half of the ion selectivity filter and the repositioning of neighboring residues known to be critical for C-type inactivation. To further confirm whether the conformational change in W434F mutant is representative of C-type inactivation in the wild-type Shaker Kv channel, we solved the structure of Shaker in 4 mM KCl, a condition known to favor inactivation. The structure of Shaker in low KCl is higher resolution than structures solved in high KCl, yet otherwise is remarkably similar to the structure of the W434F. We conclude that slow C-type inactivation in the Shaker Kv channels results in localized conformational change that disrupts potassium ion binding sites by dilating the external end of the filter.

Факторный анализ влияния микронутриентного статуса на физическое и когнитивное развитие младших школьников

Introduction. Maintenance of an adequate micronutrient status is one of the components of the children’s health with the formation of normal indicators of the physical and intellectual development. Aim. To evaluate the influence of the microelement and vitamin D adequacy of 7–8-year-old children living in the Khabarovsk Territory on their physical and cognitive development. Materials and methods. An observational, analytical, cross-sectional study was performed with an analysis of the prevalence of micronutrient imbalances among apparently healthy children aged 7–8 years living in the Khabarovsk Territory (n = 60). The physical development of children was assessed by calculating the Z-scores of body weight, height and body mass index (BMI). The assessment of the children’s cognitive abilities was carried out using conventional methods. Quantification of elements (Mg, Zn, Ca, Se, Cu, Fe, Mn, Cr) in the hair and blood serum of children was carried out by inductively coupled plasma mass spectrometry. The iodine adequacy in children was determined by its content in the first-morning urine using the cerium arsenite method. Determination of 25-hydroxyvitamin D (25(OH)D) in the blood serum of children was carried out by the enzyme-linked immunosorbent assay. Results. A slowing down in growth rates was revealed with a decrease in the content of Ca, Cu, Se, Zn, and an increase in the concentration of Fe; a decrease in BMI with deficiency of Ca, Cu, Zn, Cr, and an increase with an I and 25(OH)D intake inadequacy. A decrease in cognitive profile indicators was noted in children with deficiency of Mg, Ca, I, Cu, vitamin D, and an excess of Fe. The factor analysis using the multiple correlation method revealed a combined effect of Ca, Zn, and Fe equally on both indicators of growth and BMI parameters (p < 0.05). The cumulative effect of concentrations of Cu, Ca, I, and vitamin D in the blood serum of younger schoolchildren on the formation of short-term memory was shown (p < 0.01). A relationship was found between the level of development of verbal-logical reasoning and the concentration of Mg and Ca (p < 0.05), as well as Fe and Ca (p < 0.05), while the combination of elements with 25(OH)D in the blood serum increased the significance of correlations (p < 0.01). Conclusion. The study demonstrates the need for an integrated approach to evaluate the microelement and vitamin D adequacy in children, in connection with the presence of comorbidity of deficient and excess conditions, a combined effect on physical and cognitive development in order to prevent the development of nutritional diseases.

Implicit auditory memory in older listeners: From encoding to 6-month retention

Any listening task, from sound recognition to sound-based communication, rests on auditory memory which is known to decline in healthy ageing. However, how this decline maps onto multiple components and stages of auditory memory remains poorly characterised. In an online unsupervised longitudinal study, we tested ageing effects on implicit auditory memory for rapid tone patterns. The test required participants (younger, aged 20–30, and older adults aged 60–70) to quickly respond to rapid regularly repeating patterns emerging from random sequences. Patterns were novel in most trials (REGn), but unbeknownst to the participants, a few distinct patterns reoccurred identically throughout the sessions (REGr). After correcting for processing speed, the response times (RT) to REGn should reflect the information held in echoic and short-term memory before detecting the pattern; long-term memory formation and retention should be reflected by the RT advantage (RTA) to REGr vs REGn which is expected to grow with exposure. Older participants were slower than younger adults in detecting REGn and exhibited a smaller RTA to REGr. Computational simulations using a model of auditory sequence memory indicated that these effects reflect age-related limitations both in early and long-term memory stages. In contrast to ageing-related accelerated forgetting of verbal material, here older adults maintained stable memory traces for REGr patterns up to 6 months after the first exposure. The results demonstrate that ageing is associated with reduced short-term memory and long-term memory formation for tone patterns, but not with forgetting, even over surprisingly long timescales.

Synthesizing network dynamics for short-term memory of impulsive inputs.

Illuminating the mechanisms that the brain uses to manage and coordinate its resources is a core question in neuroscience. In particular, circuits and networks in the brain are able to encode, store and recall large amounts of information, in the service of a wide range of functionality. How do the various dynamical mechanisms within these networks allow for such coordination? We consider the specific problem of how the dynamics of networks can enact a representation of input stimuli that is retained over time, i.e., a form of short-term memory. We utilize modeling and control-theoretic methods to approach these questions, treating the state trajectory of a dynamical system as an abstract memory trace of prior inputs. The inputs impinge on the network via a variable gain, which is to be synthesized by optimization. In order to perpetuate these memory traces of stimuli, we propose that this gain is adapted to optimize: i) the error between a ground truth representation of stimuli and the encoding of them; as well as ii) overwriting of prior information. Optimizing over these central tenets of memory, we obtain a 'policy' for adapting the input gain that is dependent on the state of the network. This derived policy yields a recurrent neural network between the policy and the neural circuits, affirming existing theories that the prefrontal cortex may hold subnetworks dedicated to working memory while actively engaging with other neural subnetworks.

Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience

Psychosis in disorders like schizophrenia is commonly associated with aberrant salience and elevated striatal dopamine. However, the underlying cause(s) of this hyper-dopaminergic state remain elusive. Various lines of evidence point to glutamatergic dysfunction and impairments in synaptic plasticity in the etiology of schizophrenia, including deficits associated with the GluA1 AMPAR subunit. GluA1 knockout (Gria1−/−) mice provide a model of impaired synaptic plasticity in schizophrenia and exhibit a selective deficit in a form of short-term memory which underlies short-term habituation. As such, these mice are unable to reduce attention to recently presented stimuli. In this study we used fast-scan cyclic voltammetry to measure phasic dopamine responses in the nucleus accumbens of Gria1−/− mice to determine whether this behavioral phenotype might be a key driver of a hyper-dopaminergic state. There was no effect of GluA1 deletion on electrically-evoked dopamine responses in anaesthetized mice, demonstrating normal endogenous release properties of dopamine neurons in Gria1−/− mice. Furthermore, dopamine signals were initially similar in Gria1−/− mice compared to controls in response to both sucrose rewards and neutral light stimuli. They were also equally sensitive to changes in the magnitude of delivered rewards. In contrast, however, these stimulus-evoked dopamine signals failed to habituate with repeated presentations in Gria1−/− mice, resulting in a task-relevant, hyper-dopaminergic phenotype. Thus, here we show that GluA1 dysfunction, resulting in impaired short-term habituation, is a key driver of enhanced striatal dopamine responses, which may be an important contributor to aberrant salience and psychosis in psychiatric disorders like schizophrenia.

Central FGF21 production regulates memory but not peripheral metabolism.

SUMMARYFibroblast growth factor 21 (FGF21) is a liver-derived endocrine hormone that functions to regulate energy homeostasis and macronutrient intake. Recently, FGF21 was reported to be produced and secreted from hypothalamic tanycytes, to regulate peripheral lipid metabolism; however, rigorous investigation of FGF21 expression in the brain has yet to be accomplished. Using a mouse model that drives CRE recombinase in FGF21-expressing cells, we demonstrate that FGF21 is not expressed in the hypothalamus, but instead is produced from the retrosplenial cortex (RSC), an essential brain region for spatial learning and memory. Furthermore, we find that central FGF21 produced in the RSC enhances spatial memory but does not regulate energy homeostasis or sugar intake. Finally, our data demonstrate that administration of FGF21 prolongs the duration of long-term potentiation in the hippocampus and enhances activation of hippocampal neurons. Thus, endogenous and pharmacological FGF21 appear to function in the hippocampus to enhance spatial memory.

Aversive Associative Learning and Memory Formation by Pairing Two Chemicals in <em>Caenorhabditis elegans</em>

The nematode Caenorhabditis elegans is an attractive model organism to study learning and memory at molecular and cellular levels because of the simplicity of its nervous system, whose chemical and electrical wiring diagrams were completely reconstructed from serial electron micrographs of thin sections. Here, we describe detailed protocols for the conditioning of C. elegans by massed and spaced training for the formation of short-term memory (STM) and long-term memory (LTM), respectively. By pairing 1-propanol and hydrochloric acid as conditioned and unconditioned stimuli, respectively, C. elegans was successfully trained to form aversive associative STM and LTM. While naïve animals were attracted to 1-propanol, the trained animals were no longer or very weakly attracted to 1-propanol. Like in other organisms such as Aplysia and Drosophila, "learning and memory genes" play essential roles in memory formation. Particularly, NMDA-type glutamate receptors, expressed in only six pairs of interneurons in C. elegans, are required for the formation of both STM and LTM, possibly as a coincidence factor. Therefore, the memory trace may reside among the interneurons.

Aversive Associative Learning and Memory Formation by Pairing Two Chemicals in Caenorhabditis elegans.

The nematode Caenorhabditis elegans is an attractive model organism to study learning and memory at molecular and cellular levels because of the simplicity of its nervous system, whose chemical and electrical wiring diagrams were completely reconstructed from serial electron micrographs of thin sections. Here, we describe detailed protocols for the conditioning of C. elegans by massed and spaced training for the formation of short-term memory (STM) and long-term memory (LTM), respectively. By pairing 1-propanol and hydrochloric acid as conditioned and unconditioned stimuli, respectively, C. elegans was successfully trained to form aversive associative STM and LTM. While naïve animals were attracted to 1-propanol, the trained animals were no longer or very weakly attracted to 1-propanol. Like in other organisms such as Aplysia and Drosophila, "learning and memory genes" play essential roles in memory formation. Particularly, NMDA-type glutamate receptors, expressed in only six pairs of interneurons in C. elegans, are required for the formation of both STM and LTM, possibly as a coincidence factor. Therefore, the memory trace may reside among the interneurons.

Structure of the Shaker Kv channel and mechanism of slow C-type inactivation.

Voltage-activated potassium (Kv) channels open upon membrane depolarization and proceed to spontaneously inactivate. Inactivation controls neuronal firing rates and serves as a form of short-term memory and is implicated in various human neurological disorders. Here, we use high-resolution cryo–electron microscopy and computer simulations to determine one of the molecular mechanisms underlying this physiologically crucial process. Structures of the activated Shaker Kv channel and of its W434F mutant in lipid bilayers demonstrate that C-type inactivation entails the dilation of the ion selectivity filter and the repositioning of neighboring residues known to be functionally critical. Microsecond-scale molecular dynamics trajectories confirm that these changes inhibit rapid ion permeation through the channel. This long-sought breakthrough establishes how eukaryotic K+ channels self-regulate their functional state through the plasticity of their selectivity filters.