Multiple Trial Inhibitory Avoidance Task Research Articles

Hippocampal microRNA-mRNA regulatory network is affected by physical exercise

BackgroundIt is widely known that physical activity positively affects the overall health and brain function. Recently, microRNAs (miRNAs) have emerged as potential regulators of numerous biological processes within the brain. These molecules modulate gene expression post-transcriptionally by inducing mRNA degradation and inhibiting the translation of target mRNAs. MethodsTo verify whether the procognitive effects of physical exercise are accompanied by changes in the activity of miRNA-mRNA network in the brain, differential expression analysis was performed in the hippocampus of control (CTL) and exercised (Ex) rats subjected to 4 weeks of treadmill exercise. Cognition was evaluated by a multiple trial inhibitory avoidance (MTIA) task and Illumina next-generation sequencing (NGS) was used for miRNA and mRNA profiling. ResultsExercise improved memory retention but not acquisition in the MTIA task. It was observed that 4 miRNAs and 54 mRNAs were significantly altered in the hippocampus of Ex2 (euthanized 2 h after the last exercise bout) group when compared to CTL group. Bioinformatic analysis showed an inverse correlation between 3 miRNAs and 6 target mRNAs. The miRNAs miR-129-1-3p and miR-144-5p were inversely correlated to the Igfbp5 and Itm2a, respectively, and the miR-708-5p presented an inverse correlation with Cdkn1a, Per2, Rt1-a2. ConclusionThe exercise-induced memory improvements are accompanied by changes in hippocampal miRNA-mRNA regulatory network. General significancePhysical exercise can affect brain function through modulation of epigenetics mechanisms involving miRNA regulation.

Lithium Prevents REM Sleep Deprivation-Induced Impairments on Memory Consolidation

Pre-training rapid eye movement sleep (REMS) deprivation affects memory acquisition and/or consolidation. It also produces major REMS rebound at the cost of waking and slow wave sleep (SWS). Given that both SWS and REMS appear to be important for memory processes, REMS rebound after training may disrupt the organization of sleep cycles, i.e., excessive amount of REMS and/or little SWS after training could be harmful for memory formation. To examine whether lithium, a drug known to increase SWS and reduce REMS, could prevent the memory impairment induced by pre-training sleep deprivation. Animals were divided in 2 groups: cage control (CC) and REMS-deprived (REMSDep), and then subdivided into 4 subgroups, treated either with vehicle or 1 of 3 doses of lithium (50, 100, and 150 mg/kg) 2 h before training on the multiple trial inhibitory avoidance task. Animals were tested 48 h later to make sure that the drug had been already metabolized and eliminated. Another set of animals was implanted with electrodes and submitted to the same experimental protocol for assessment of drug-induced sleep-wake changes. Wistar male rats weighing 300-400 g. Sleep deprived rats required more trials to learn the task and still showed a performance deficit during test, except from those treated with 150 mg/kg of lithium, which also reduced the time spent in REM sleep during sleep recovery. Lithium reduced rapid eye movement sleep and prevented memory impairment induced by sleep deprivation. These results indicate that these phenomena may be related, but cause-effect relationship cannot be ascertained.

Effects of an SSRI on sleep architecture and memory in an animal model of depression

Event Abstract Back to Event Effects of an SSRI on sleep architecture and memory in an animal model of depression Paula A. Tiba1*, Vanessa Conttato-Rossi1, Ricardo Borges-Machado1, Karin-di Monteiro-Moreira1, Maria-Gabriela Menezes-Oliveira1, Sergio Tufik1 and Deborah Suchecki1 1 UNIFESP, Brazil Although several studies have demonstrated the relationship between sleep and memory, one of the strongest arguments to refute this hypothesis is based on the demonstration that antidepressant drugs markedly inhibit or suppress REM sleep in depressive subjects with no consequent detrimental effects on cognition. It is important to note, however, that depressive patients spend more time in REM sleep; nonetheless, memory impairment is often reported. The medication could, therefore, normalize REM sleep and, at the same time, improve memory performance. No work has investigated the effects of SSRI treatment on both sleep and memory, comparing normal and depressive patients. The aim of the present study was to compare the effects of citalopram on sleep and memory between a spontaneous animal model of depression (Wistar-Kyoto rats) and normal controls. Sleep was recorded at baseline condition and the animals were allocated into one of four groups: Kyoto+Citalopram (KC); Kyoto+Vehicle (KV); Wistar+Citalopram (WC) or Wistar+Vehicle (WV). Treatment lasted 21 days, after which the training in the Multiple Trial Inhibitory Avoidance task occurred. Test was performed on the next day. Sleep recordings were carried out after the first and last days of treatment, as well as after training and testing. As reported previously, KV animals presented more REM sleep than Wistar rats, and acute SSRI treatment reduced this parameter to Wistar levels. Interestingly, strain- or treatment-dependent sleep alterations were only observed when a challenge was present, such as the first day of treatment, and after training. The treatment had no effect on normal Wistar rats. Although memory acquisition was impaired in KC rats, sleep alterations did not support a causal relationship between sleep amount and memory, since REM sleep was the same in Kyoto and Wistar animals, whereas memory performance was impaired in the former. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Tiba PA, Conttato-Rossi V, Borges-Machado R, Monteiro-Moreira K, Menezes-Oliveira M, Tufik S and Suchecki D (2009). Effects of an SSRI on sleep architecture and memory in an animal model of depression. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.321 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Jun 2009; Published Online: 15 Jun 2009. * Correspondence: Paula A Tiba, UNIFESP, São Paulo, Brazil, paula.tiba@ufabc.edu.br Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Paula A Tiba Vanessa Conttato-Rossi Ricardo Borges-Machado Karin-di Monteiro-Moreira Maria-Gabriela Menezes-Oliveira Sergio Tufik Deborah Suchecki Google Paula A Tiba Vanessa Conttato-Rossi Ricardo Borges-Machado Karin-di Monteiro-Moreira Maria-Gabriela Menezes-Oliveira Sergio Tufik Deborah Suchecki Google Scholar Paula A Tiba Vanessa Conttato-Rossi Ricardo Borges-Machado Karin-di Monteiro-Moreira Maria-Gabriela Menezes-Oliveira Sergio Tufik Deborah Suchecki PubMed Paula A Tiba Vanessa Conttato-Rossi Ricardo Borges-Machado Karin-di Monteiro-Moreira Maria-Gabriela Menezes-Oliveira Sergio Tufik Deborah Suchecki Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Hippocampal infusions of pyruvate reverse the memory-impairing effects of septal muscimol infusions

Hippocampal infusions of glucose reverse memory deficits in spontaneous alternation and in a continuous multiple trial inhibitory avoidance task. The current experiments tested whether glucose metabolism may participate in these effects of glucose. Specifically, these experiments determined whether the glycolytic metabolite pyruvate would mimic these effects of glucose. Male Sprague–Dawley rats were given septal infusions of vehicle or the gamma-aminobutyric acid (GABA) receptor agonist muscimol (0.15 nmol for spontaneous alternation or 5 nmol for continuous multiple trial inhibitory avoidance) combined with hippocampal infusions of vehicle or pyruvate (200 nmol) 15 min prior to assessing spontaneous alternation or training in a continuous multiple trial inhibitory avoidance task. The infusions of muscimol decreased percent alternation scores and continuous multiple trial inhibitory avoidance retention latencies tested 48 h after training. More importantly, hippocampal infusions of pyruvate reversed the deficits produced by septal infusions of muscimol on both tasks. These findings show for the first time that hippocampal infusions of pyruvate influence memory and suggest that glucose may affect memory via glycolytic metabolism.

Infusions of physostigmine into the hippocampus or the entorhinal cortex attenuate avoidance retention deficits produced by intra-septal infusions of the GABA agonist muscimol

Septal γ-aminobutyric acid (GABA) receptor activation is known to disrupt memory formation, although the mechanisms underlying this impairment remain unclear. The present study explored the possibility that high levels of septal GABA receptor activity might impair memory by down-regulating acetylcholine (ACh) function in archicortex and entorhinal cortex. To test this possibility, rats were trained on an avoidance task 15 min after receiving intra-septal infusions of vehicle or muscimol (5 nmol/0.5 μl) combined with unilateral intra-hippocampal (10 μl/1 μl) or intra-entorhinal cortex (1.875 μg/0.25 μl) infusions of vehicle or the acetylcholinesterase inhibitor physostigmine. We demonstrate that these infusions do not alter acquisition performance on a continuous multiple trial inhibitory avoidance task. However, intra-septal infusions of muscimol dramatically impair retention performance 48 h later. More importantly, infusions of physostigmine into the hippocampus or the entorhinal cortex, at doses that do not influence acquisition or retention performance when infused alone, attenuate the impairing effects of the muscimol infusions on retention. We suggest that high levels of septal GABA receptor activity might impair memory by down-regulating ACh levels in the hippocampal region, and that such memory impairments can be ameliorated by increasing ACh levels in the hippocampus or entorhinal cortex.

Bicuculline administered into the amygdala after training blocks benzodiazepine-induced amnesia

Male Sprague-Dawley rats were injected (i.p.) with either midazolam (MDZ 2.0 mg/kg) or vehiele (1.0 ml/kg) 10 min before they were trained on a multiple-trial inhibitory avoidance task. Immediately following the training, bicuculline methiodide (BMI: 2.0, 5.6, 56.0 or 197.0 pmol/0.5 μl) or vehicle (0.5 μl) was infused bilaterally into the amygdala. On a 48 h retention test the performance of the MDZ-treated animals was significantly poorer than that of controls. The retention of MDZ-treated animals given intra-amygdala injections of the lowest dose of BMI (2.0 pmol) was comparable to that of controls, whereas higher doses of BMI impaired retention. The present results are consistent with other findings indicating that the amygdala mediates the amnestic effects of benzodiazepines on aversive learning. Furthermore, these data suggest that benzodiazepines impair memory by disrupting post-training processes underlying memory consilidation.

Infusion of the GABAergic antagonist bicuculline into the medial septal area does not block the impairing effects of systemically administered midazolam on inhibitory avoidance retention

This experiment investigated the effect of intraseptal administration of the GABAergic antagonist bicuculline methiodide on benzodiazepine-induced amnesia. Male Sprague-Dawley rats were implanted with cannula aimed at the medial septal area and allowed to recover for 1 week. Ten minutes prior to training in a continuous multiple trial inhibitory avoidance task, buffer solution or bicuculline methiodide (56 or 100 pmol/0.5 microliter) was injected into the medial septal area. This infusion was immediately followed by systemic (ip) administration of saline or midazolam (1.5 or 3.0 mg/kg). In comparison with saline controls, animals given the higher dose of midazolam (3.0 mg/kg), required more trials to reach acquisition criterion (remaining in the starting chamber for 100 s). This midazolam-induced acquisition deficit was blocked by an intraseptal infusion of bicuculline methiodide (100 pmol). On a 48-h retention test the performance of animals given either dose of midazolam was significantly impaired relative to vehicle controls. Furthermore, although intraseptal infusion of bicuculline methiodide prior to systemic injection of midazolam blocked the midazolam-induced acquisition impairment, bicuculline did not block the midazolam-induced retention impairment. These results suggest that although the medial septal area may be involved in midazolam-induced acquisition deficits, this area is not a critical site of action for benzodiazepine-induced effects on inhibitory avoidance retention.

Memory of rats with amygdala lesions induced 30 days after footshock-motivated escape training reflects degree of original training.

This experiment was conducted to determine whether the amount of preoperative training influences the effects, on retention, of amygdala lesions induced 30 days after escape training. Rats received 1 or 10 footshock-motivated escape training trials; 30 days later, sham or neurotoxic amygdala lesions were induced. Results of an inhibitory avoidance test performed 4 days after surgery indicated that amygdala lesions impaired retention performance; however, increased preoperative training partially attenuated the retention deficit. Increased preoperative training also attenuated the impairing effects of the lesions on retention assessed in a continuous multiple-trial inhibitory avoidance task given 36 days after the original escape training. The finding that amygdala-lesioned rats remembered the escape training suggests that the amygdala is not a critical locus of the changes underlying the long-term retention of footshock-motivated escape training.

Bicuculline administered into the amygdala blocks benzodiazepine-induced amnesia

This experiment investigated the effect of intra-amygdala administration of the GABAergic antagonist bicuculline methiodide on benzodiazepine-induced amnesia. Male Sprague-Dawley rats were implanted bilaterally with cannulae aimed at the amygdala and allowed to recover for 1 week. Ten minutes before training in a continuous multiple trial inhibitory avoidance task a buffer solution or bicuculline methiodide (56 pmol/0.5 microliters) was injected bilaterally into the amygdala and this injection was immediately followed by a systemic injection of saline or midazolam (1.0 mg/kg). In comparison with saline controls, midazolam-treated animals required more trials to reach the acquisition criterion of remaining in the starting chamber for 100 s. The midazolam effect on acquisition was not attenuated by intra-amygdala infusion of bicuculline methiodide, suggesting that the midazolam-induced changes in acquisition behavior do not involve the amygdaloid GABAergic system. On a 48-h retention test the performance of the midazolam-treated animals was significantly poorer than that of the controls. However, the retention performance of animals given intra-amygdala injections of bicuculline methiodide prior to the systemic injection of midazolam was comparable to that of the saline controls. These results suggest that the amygdaloid GABAergic system mediates the impairing effects of midazolam on retention of inhibitory avoidance training.