Relating Neurochemical Changes Associated with THC Use to Learning and Memory in Adolescent Rats

Mapping Intimacies ◽

10.26686/wgtn.16993084 ◽

2021 ◽

Author(s):

◽

Ryan William Johnstone Steel

Keyword(s):

Learning And Memory ◽

Short Term Memory ◽

Learning Task ◽

Cannabis Use ◽

Synaptic Activity ◽

Rate Of Learning ◽

Adolescent Rats ◽

Neurochemical Changes ◽

Newborn Neurons ◽

Neurochemical Correlates

<p>Cannabis is the most widely used illicit drug. Adolescents may be especially vulnerable to the effects of cannabis, and alarmingly, adolescence is also a period of heavy cannabis use. However, few studies have investigated the cognitive effects of cannabis use in adolescents specifically. Furthermore, the neurochemical correlates of cognitive impairment associated with cannabis use at any age have received very little experimental attention. This research project sought to address these shortcomings in the literature using THC, the major psychoactive component of cannabis, and a rat model of adolescence. The rate of learning was slower in THC-treated animals, and this was attributable to deficits in the cognitive function of 'chunking', a process by which the information capacity of short-term memory is enlarged. Impairment of chunking by cannabinoids has not been previously reported. Behavioural impairment by THC was associated with impaired hippocampal plasticity, including changes in synaptic activity and architecture, as well as changes in neurogenesis. The attenuation of structural and functional plasticity in the hippocampus in response to training in a learning task was more pronounced than the subtle effects of THC-treatment on the survival and early development of newborn neurons. Importantly, no effects of THC were seen in animals not trained in the maze. Thus, plasticity is more sensitive to the effects of THC during times of learning, and this greater sensitivity likely accounts for the behavioural impairment associated with cannabis use. The data presented in this thesis add significantly to the existing literature by identifying novel behavioural and neurochemical processes by which cannabis use may impair learning and memory. Whether these impairments represent a greater sensitivity of adolescents to THC remains to be determined.</p>

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Relating Neurochemical Changes Associated with THC Use to Learning and Memory in Adolescent Rats

10.26686/wgtn.16993084.v1 ◽

2021 ◽

Author(s):

◽

Ryan William Johnstone Steel

Keyword(s):

Learning And Memory ◽

Short Term Memory ◽

Learning Task ◽

Cannabis Use ◽

Synaptic Activity ◽

Rate Of Learning ◽

Adolescent Rats ◽

Neurochemical Changes ◽

Newborn Neurons ◽

Neurochemical Correlates

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Role of MicroRNA Genes miR-1000 and miR-375 in Forming Olfactory Conditional Memory in Drosophila melanogaster

MicroRNA ◽

10.2174/2211536609666200204113403 ◽

2020 ◽

Vol 09 ◽

Author(s):

Sadniman Rahman ◽

Chaity Modak ◽

Mousumi Akter ◽

Mohammad Shamimul Alam

Keyword(s):

Learning And Memory ◽

Short Term Memory ◽

Memory Loss ◽

Memory Formation ◽

Neural Integration ◽

Significant Difference ◽

Locomotion Speed ◽

Microrna Genes ◽

With Memory

Background: Learning and memory is basic aspects in neurogenetics as most of the neurological disorders start with dementia or memory loss. Several genes associated with memory formation have been discovered. MicroRNA genes miR-1000 and miR-375 were reported to be associated with neural integration and glucose homeostasis in some insects and vertebrates. However, neuronal function of these genes is yet to be established in D. melanogaster. Objective: Possible role of miR-1000 and miR-375 in learning and memory formation in this fly has been explored in the present study. Methods: Both appetitive and aversive olfactory conditional learning were tested in the miR-1000 and miR-375 knockout (KO) strains and compared with wild one. Five days old third instar larvae were trained by allowing them to be associated with an odor with reward (fructose) or punishment (salt). Then, the larvae were tested to calculate their preferences to the odor trained with. Learning index (LI) values and larval locomotion speed were calculated for all strains. Results: No significant difference was observed for larval locomotion speed in mutant strains. Knockout strain of miR-1000 showed significant deficiency in both appetitive and aversive memory formation whereas miR-375 KO strain showed a significantly lower response only in appetitive one. Conclusion: The results of the present study indicate important role played by these two genes in forming short-term memory in D. melanogaster.

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23.2 ALCOHOL USE DISORDER VS CANNABIS USE DISORDER SYMPTOMATOLOGY IN ADOLESCENTS IS DIFFERENTIALLY ASSOCIATED WITH DYSFUNCTIONS IN NEURAL REPRESENTATIONS OF PREDICTION ERROR FOLLOWING EXPLORATION OF NOVEL STIMULI IN AN INSTRUMENTAL LEARNING TASK

Journal of the American Academy of Child & Adolescent Psychiatry ◽

10.1016/j.jaac.2020.08.226 ◽

2020 ◽

Vol 59 (10) ◽

pp. S197

Author(s):

Joseph Aloi ◽

Kathleen I. Crum ◽

Karina S. Blair ◽

James Blair

Keyword(s):

Alcohol Use ◽

Prediction Error ◽

Alcohol Use Disorder ◽

Instrumental Learning ◽

Learning Task ◽

Cannabis Use ◽

Cannabis Use Disorder ◽

Neural Representations

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The Making of Long-Lasting Memories: A Fruit Fly Perspective

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.662129 ◽

2021 ◽

Vol 15 ◽

Author(s):

Camilla Roselli ◽

Mani Ramaswami ◽

Tamara Boto ◽

Isaac Cervantes-Sandoval

Keyword(s):

Learning And Memory ◽

Neural Activity ◽

Molecular Mechanisms ◽

De Novo ◽

Fruit Fly ◽

Memory Formation ◽

Synaptic Activity ◽

Model Organisms ◽

Transient Wave ◽

Control Of Gene Expression

Understanding the nature of the molecular mechanisms underlying memory formation, consolidation, and forgetting are some of the fascinating questions in modern neuroscience. The encoding, stabilization and elimination of memories, rely on the structural reorganization of synapses. These changes will enable the facilitation or depression of neural activity in response to the acquisition of new information. In other words, these changes affect the weight of specific nodes within a neural network. We know that these plastic reorganizations require de novo protein synthesis in the context of Long-term memory (LTM). This process depends on neural activity triggered by the learned experience. The use of model organisms like Drosophila melanogaster has been proven essential for advancing our knowledge in the field of neuroscience. Flies offer an optimal combination of a more straightforward nervous system, composed of a limited number of cells, and while still displaying complex behaviors. Studies in Drosophila neuroscience, which expanded over several decades, have been critical for understanding the cellular and molecular mechanisms leading to the synaptic and behavioral plasticity occurring in the context of learning and memory. This is possible thanks to sophisticated technical approaches that enable precise control of gene expression in the fruit fly as well as neural manipulation, like chemogenetics, thermogenetics, or optogenetics. The search for the identity of genes expressed as a result of memory acquisition has been an active interest since the origins of behavioral genetics. From screenings of more or less specific candidates to broader studies based on transcriptome analysis, our understanding of the genetic control behind LTM has expanded exponentially in the past years. Here we review recent literature regarding how the formation of memories induces a rapid, extensive and, in many cases, transient wave of transcriptional activity. After a consolidation period, transcriptome changes seem more stable and likely represent the synthesis of new proteins. The complexity of the circuitry involved in memory formation and consolidation is such that there are localized changes in neural activity, both regarding temporal dynamics and the nature of neurons and subcellular locations affected, hence inducing specific temporal and localized changes in protein expression. Different types of neurons are recruited at different times into memory traces. In LTM, the synthesis of new proteins is required in specific subsets of cells. This de novo translation can take place in the somatic cytoplasm and/or locally in distinct zones of compartmentalized synaptic activity, depending on the nature of the proteins and the plasticity-inducing processes that occur. We will also review recent advances in understanding how localized changes are confined to the relevant synapse. These recent studies have led to exciting discoveries regarding proteins that were not previously involved in learning and memory processes. This invaluable information will lead to future functional studies on the roles that hundreds of new molecular actors play in modulating neural activity.

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Thrombopoietin Receptor Agonist Eltrombopag Prevents Insulin Resistance and Synaptic Pathology via HIF1α/COX2/Sirt1 Signaling Pathway

10.21203/rs.3.rs-308317/v1 ◽

2021 ◽

Author(s):

he yu ◽

xuebao wang ◽

leping liu ◽

baihui chen ◽

shuya feng ◽

...

Keyword(s):

Insulin Resistance ◽

Learning And Memory ◽

Receptor Agonist ◽

Synaptic Activity ◽

Sirtuin 1 ◽

High Dose ◽

Thrombopoietin Receptor ◽

Thrombopoietin Receptor Agonist ◽

Synaptic Formation

Abstract Background: Insulin resistance has been reported to be closely correlated with the pathogenesis of MHE. The mechanism underlying the effects of thrombopoietin receptor agonist eltrombopag (ELT) on synaptic activity and formation involved in MHE pathogenesis remains unclear. Methods: The effect of ELT on neurodegeneration and insulin resistance was examined in the primary rat neurons and an MHE rat model. Results: We found that the level of thrombopoietin receptor c-MPL (MPL) expression was decreased in MHE brains, and ELT administration improved insulin resistance, alleviated the destruction of synaptic formation and enhanced learning and memory in the MHE rats, indicating the relationship between dowregulated ELT and insulin resistance. Then in vitro, ELT treatment ameliorated the impairment of glucose uptake, indicating the reduction of insulin resistance. High dose of glucose inhibited insulin-stimulated downregulation of Hypoxia-inducible factor-1α (HIF1α) expression, the inhibition of inflammatory response and upregulation of sirtuin-1 (Sirt1), destruction of synaptic formation and activity, which were all reversed by ELT treatment in insulin resistant neurons.Conclusions: These results indicate that ELT is a promising potential therapeutic agent for insulin resistance and defect in learning and memory.

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Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior

10.1101/2021.09.12.21263466 ◽

2021 ◽

Author(s):

Margaret L. Westwater ◽

Alexander G. Murley ◽

Kelly M.J. Diederen ◽

T. Adrian Carpenter ◽

Hisham Ziauddeen ◽

...

Keyword(s):

Eating Disorders ◽

Bulimia Nervosa ◽

Binge Eating ◽

Instrumental Learning ◽

Learning Task ◽

Resonance Spectroscopy ◽

Binge Eating Disorders ◽

Habitual Behavior ◽

Neurochemical Changes ◽

The Right

AbstractBackgroundAnorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered brain structure and function, as well as increased habitual behavior. This neurobehavioral profile may implicate neurochemical changes in the pathogenesis of these illnesses. Altered glutamate, myo-inositol and N-acetyl aspartate (NAA) concentrations are reported in restrictive AN, yet whether these extend to binge-eating disorders, or relate to habitual traits in affected individuals, remains unknown.MethodsUsing single-voxel proton magnetic resonance spectroscopy, we measured glutamate, myo-inositol and NAA in 85 women [n=22 AN (binge-eating/purging subtype; AN-BP), n=33 BN, n=30 controls]. Spectra were acquired from the right inferior lateral prefrontal cortex and the right occipital cortex. To index habitual behavior, participants performed an instrumental learning task and completed the Creature of Habit Scale. Exploratory analyses examined associations between metabolites and habitual behavior.ResultsWomen with AN-BP, but not BN, had reduced myo-inositol and NAA concentrations relative to controls in both voxels. Patient groups had intact performance on the instrumental learning task; however, both groups reported increased routine behaviors compared to controls. Women with BN also reported greater automatic behaviors, and automaticity was related to reduced prefrontal glutamate and NAA in the AN-BP group.DiscussionFindings extend previous reports of reduced myo-inositol and NAA levels in AN to AN-BP, which may reflect disrupted axonal-glial signaling. Although we found inconsistent support for increased habitual behavior in AN-BP and BN, we identified preliminary associations between prefrontal metabolites and automaticity in AN-BP. These results provide further evidence of unique neurobiological profiles across binge-eating disorders.

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AMPA receptors in the synapse turnover by monomer diffusion

Nature Communications ◽

10.1038/s41467-019-13229-8 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Jyoji Morise ◽

Kenichi G. N. Suzuki ◽

Ayaka Kitagawa ◽

Yoshihiko Wakazono ◽

Kogo Takamiya ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Plasma Membrane ◽

Synaptic Plasticity ◽

Learning And Memory ◽

Ampa Receptors ◽

Single Molecules ◽

Lateral Diffusion ◽

Synaptic Function ◽

Synaptic Activity ◽

Monomer Diffusion

AbstractThe number and subunit compositions of AMPA receptors (AMPARs), hetero- or homotetramers composed of four subunits GluA1–4, in the synapse is carefully tuned to sustain basic synaptic activity. This enables stimulation-induced synaptic plasticity, which is central to learning and memory. The AMPAR tetramers have been widely believed to be stable from their formation in the endoplasmic reticulum until their proteolytic decomposition. However, by observing GluA1 and GluA2 at the level of single molecules, we find that the homo- and heterotetramers are metastable, instantaneously falling apart into monomers, dimers, or trimers (in 100 and 200 ms, respectively), which readily form tetramers again. In the dendritic plasma membrane, GluA1 and GluA2 monomers and dimers are far more mobile than tetramers and enter and exit from the synaptic regions. We conclude that AMPAR turnover by lateral diffusion, essential for sustaining synaptic function, is largely done by monomers of AMPAR subunits, rather than preformed tetramers.

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Short-Term Memory Deficits in the SLEEP Inbred Panel

Clocks & Sleep ◽

10.3390/clockssleep1040036 ◽

2019 ◽

Vol 1 (4) ◽

pp. 471-488 ◽

Cited By ~ 1

Author(s):

Shailesh Kumar ◽

Kirklin R. Smith ◽

Yazmin L. Serrano Negron ◽

Susan T. Harbison

Keyword(s):

Learning And Memory ◽

Sleep Duration ◽

Genetic Architecture ◽

Short Term Memory ◽

Morphological Changes ◽

Brain Structures ◽

Social Conditions ◽

Short Term ◽

The Relationship ◽

The Brain

Although sleep is heritable and conserved across species, sleep duration varies from individual to individual. A shared genetic architecture between sleep duration and other evolutionarily important traits could explain this variability. Learning and memory are critical traits sharing a genetic architecture with sleep. We wanted to know whether learning and memory would be altered in extreme long or short sleepers. We therefore assessed the short-term learning and memory ability of flies from the Sleep Inbred Panel (SIP), a collection of 39 extreme long- and short-sleeping inbred lines of Drosophila. Neither long nor short sleepers had appreciable learning, in contrast to a moderate-sleeping control. We also examined the response of long and short sleepers to enriched social conditions, a paradigm previously shown to induce morphological changes in the brain. While moderate-sleeping control flies had increased daytime sleep and quantifiable increases in brain structures under enriched social conditions, flies of the Sleep Inbred Panel did not display these changes. The SIP thus emerges as an important model for the relationship between sleep and learning and memory.

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Selective memory and behavioral alterations after ambient ultrafine particulate matter exposure in aged 3xTgAD Alzheimer’s disease mice

Particle and Fibre Toxicology ◽

10.1186/s12989-019-0323-3 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 6

Author(s):

Katrina Jew ◽

Denise Herr ◽

Candace Wong ◽

Andrea Kennell ◽

Keith Morris-Schaffer ◽

...

Keyword(s):

Locomotor Activity ◽

Learning And Memory ◽

Spatial Learning ◽

Short Term Memory ◽

Memory Deficits ◽

Olfactory Discrimination ◽

Spatial Learning And Memory ◽

Short Term ◽

Term Memory ◽

Appetitive Motivation

Abstract Background A growing body of epidemiological literature indicates that particulate matter (PM) air pollution exposure is associated with elevated Alzheimer’s disease (AD) risk and may exacerbate AD-related cognitive decline. Of concern is exposure to the ultrafine PM (UFP) fraction (≤100 nm), which deposits efficiently throughout the respiratory tract, has higher rates of translocation to secondary organs, like brain, and may induce inflammatory changes. We, therefore, hypothesize that exposure to UFPs will exacerbate cognitive deficits in a mouse model of AD. The present study assessed alterations in learning and memory behaviors in aged (12.5 months) male 3xTgAD and non-transgenic mice following a 2-week exposure (4-h/day, 4 days/week) to concentrated ambient UFPs using the Harvard ultrafine concentrated ambient particle system (HUCAPS) or filtered air. Beginning one month following exposure, locomotor activity, spatial learning and memory, short-term recognition memory, appetitive motivation, and olfactory discrimination were assessed. Results No effects on locomotor activity were found following HUCAPS exposure (number concentration, 1 × 104–4.7 × 105 particles/cm3; mass concentration, 29–132 μg/m3). HUCAPS-exposed mice, independent of AD background, showed a significantly decreased spatial learning, mediated through reference memory deficits, as well as short-term memory deficits in novel object recognition testing. AD mice displayed diminished spatial working memory, potentially a result of olfactory deficits, and short-term memory. AD background modulated HUCAPS-induced changes on appetitive motivation and olfactory discrimination, specifically enhancing olfactory discrimination in NTg mice. Modeling variation in appetitive motivation as a covariate in spatial learning and memory, however, did not support the conclusion that differences in motivation significantly underlie changes in spatial learning and memory. Conclusions A short-term inhalation exposure of aged mice to ambient UFPs at human-relevant concentrations resulted in protracted (testing spanning 1–6.5 months post-exposure) adverse effects on multiple memory domains (reference and short-term memory) independent of AD background. Impairments in learning and memory were present when accounting for potential covariates like motivational changes and locomotor activity. These results highlight the need for further research into the potential mechanisms underlying the cognitive effects of UFP exposure in adulthood.

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