Trial Inhibitory Avoidance Research Articles

Inhibitors of cellular stress overcome acute effects of ethanol on hippocampal plasticity and learning

Ethanol intoxication can produce marked changes in cognitive function including states in which the ability to learn and remember new information is completely disrupted. These defects likely reflect changes in the synaptic plasticity thought to underlie memory formation. We have studied mechanisms contributing to the adverse effects of ethanol on hippocampal long-term potentiation (LTP) and provided evidence that ethanol-mediated LTP inhibition involves a form of metaplasticity resulting from local metabolism of ethanol to acetaldehyde and untimely activation of N-methyl-d-aspartate receptors (NMDARs), both of which are neuronal stressors. In the present studies, we sought to understand the role of cellular stress in LTP defects, and demonstrate that ethanol's effects on LTP in the CA1 hippocampal region are overcome by agents that inhibit cellular stress responses, including ISRIB, a specific inhibitor of integrated stress responses, and GW3965, an agonist that acts at liver X receptors (LXRs) and dampens cellular stress. The agents that alter LTP inhibition also prevent the adverse effects of acute ethanol on one trial inhibitory avoidance learning. Unexpectedly, we found that the LXR agonist but not ISRIB overcomes effects of ethanol on synaptic responses mediated by N-methyl-d-aspartate receptors (NMDARs). These results have implications for understanding the adverse effects of ethanol and possibly for identifying novel paths to treatments that can prevent or overcome ethanol-induced cognitive dysfunction.

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.

A1 adenosine receptors in the striatum play a role in the memory impairment caused by sleep deprivation through downregulation of the PKA pathway.

Sleep deprivation is known to affect memory formation, but how it interacts with different memory systems is not completely understood. Adenosine, a homeostatic regulator of sleep that has an increased extracellular concentration during sleep deprivation, is one of the neuromodulators that may be involved in this interaction. The A1 adenosine receptor is involved in both sleep regulation and memory formation. Among other pathways, the A1 receptor decreases cAMP levels in the cytosol and thus also regulates protein kinase A (PKA) and exchange protein activated by cAMP (EPAC) activity. To verify the role of the A1 receptor in the memory impairment caused by sleep deprivation, we tested the effect of 96 h of sleep deprivation (SD) and the administration of DPCPX, an A1 receptor antagonist on male Wistar rats prior to the training sessions for two memory tasks that relies on the hippocampal function: the multiple trial inhibitory avoidance (MTIA) task, which also requires the striatum, and the contextual fear conditioning (CFC) task, which does not. We also evaluated the effect of SD, DPCPX and the MTIA training session on the protein expression levels of the A1 receptor, PKA phosphorylation and EPAC activity in both the hippocampus and the striatum. Sleep deprivation impaired the performance in the test sessions of both tasks; DPCPX was able to prevent the impairment in the MTIA test but not in the CFC test. SD increased A1 receptor protein expression levels in the striatum but not in the hippocampus and also decreased PKA phosphorylation in both structures; DPCPX prevented this decrease in the striatum, but not in the hippocampus. Finally, SD had no effect on EPAC activity in either of the structures. These results indicate that the A1 adenosine receptors play a role in the memory impairment caused by sleep deprivation in tasks that involve the striatum through modulation of the cAMP/PKA pathway.

Multiple trial inhibitory avoidance acquisition and retrieval are resistant to chronic stress

Chronic mild stress (CMS) is a widely accepted animal model relevant to depression that among other consequences, is chiefly known to induce anhedonia, often assessed as decreased preference for sucrose solution. CMS is also known to affect cognition, particularly memory tasks. In this study we have employed the multiple-trial inhibitory avoidance memory task (MTIA) to assess CMS effects on memory acquisition and retrieval. MTIA consists of repeated exposures to the unconditioned stimulus until a learning criterion is reached. Wistar rats underwent CMS for 5 weeks, and sucrose consumption was assessed once a week. At the end of CMS, animals were evaluated in the MTIA task. Overall decreased sucrose solution preference was highly variable. Further analyses showed that a subset of animals expressed resilience while another subset was sensitive to stress. CMS did not affect the number of acquisition sessions before reaching criterion or retrieval latency of MTIA task in neither sensitive nor resilient groups. Although tasks that assess learning ability in animal models relevant to depression indicate cognitive deficits, the ability to learn the association between compartment crossing and the aversive electric foot shock, which is strongly dependent on emotional aspects, was intact.

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.

Learning‐dependent plasticity of hippocampal CA1 pyramidal neuron postburst afterhyperpolarizations and increased excitability after inhibitory avoidance learning depend upon basolateral amygdala inputs

Hippocampal pyramidal neurons in vitro exhibit transient learning-dependent reductions in the amplitude and duration of calcium-dependent postburst afterhyperpolarizations (AHPs), accompanied by other increases in excitability (i.e., increased firing rate, or reduced spike-frequency accommodation) after trace eyeblink conditioning or spatial learning, with a time-course appropriate to support consolidation of the learned tasks. Both these tasks require multiple days of training for acquisition. The hippocampus also plays a role in acquisition of single trial inhibitory avoidance learning. The current study assessed AHP plasticity in this single-trial learning task using in vitro tissue slices prepared at varying intervals posttrial using intracellular current-clamp recordings. Reduced AHPs and reduced accommodation were seen in ventral CA1 pyramidal neurons within 1 h posttraining, plasticity which persisted 24 h but was extinguished >72 h posttrial. There was also a reduction in ventral CA1 AHPs and accommodation 1 h following simple exposure to the IA apparatus (a novel context) but this change was extinguished by 24 h postexposure. Reductions in AHPs and accommodation were also seen in dorsal CA1 pyramidal neurons, but were delayed until 24 h posttrial and extinguished at >72 h posttrial. Finally, transient inactivation of the basolateral complex of the amygdala (with the local anesthetics lidocaine or bupivacaine) either immediately before or immediately posttrial blocked both learning and learning-dependent changes in excitability in the hippocampus assessed 24 h posttrial. CA3 pyramidal neurons showed no reductions in AHP peak amplitude or accommodation following IA training or context exposure.

Effects of propofol on cyclic AMP response element binding protein phosphorylation and cyclic AMP response element binding protein mRNA expression in hippocampus of rats

Objective to investigate the effects of propofol on cyclic AMP response element binding protein (CREB) phosphorylation and CREB mRNA expression in hippocampus of rats. Methods Sixty -four male Sprague -Dawley (SD) rats weighting 250 g-280 g were randomly divided into 2 groups (n=32) with Randomization Adviser 1.0 software: normal saline treated (Group S) and propofol treated (Group P). Animals of both groups underwent a continuous multiple -trial inhibitory avoidance training. The times of trial needed for each animal to attain the learning criterion( 100 seconds) were recorded. Each animal was given intraperitoneal propofol 9 mg/kg or normal saline 2 ml/kg at 15 min before training. The memory retention was tested at 1, 3 and 24 h( n=8, at each time point) after the training session and the memory latency was recorded. Animals were sacrificed at 15 min after reagent administration (T0) and after the memory testing (T1～3). Hippocampus was obtained to determine the phosphorylation of CRKB (pCREB) and CREB mRNA expression. Results The times of trials required for the rats to learn the task in Group S and Group P is 1 (0.25) and 3 (1.25), respectively. Learning ability was significantly impaired in rats of Group P(P<0.01 ). Rats of Group S had a median retention latency more than 300 s at each memory testing. The median retention latency of rats in Group P at T1, T2and T3 was 319( 144) s, 131( 114) s and 56(30) s, respectively. Compared with group S, there was a decrease of CREB phosphorylation expression at T0-3 in Group P (P<0.01). The CREB mRNA expression in Group P was decreased at T3 (P<0.01). Conclusion Propofol can inhibit CREB phosphorylation, and downregulate CREB mRNA expression in hippocampus of rats. Key words: Propofol; DNA-binding protein, cyclic AMP-responsive; Hippocampus

The effect of acute restraint stress and dexamethasone on retrieval of long-term memory in rats: an interaction with opiate system

This study investigated whether application of acute restraint stress or dexamethasone, as a glucocorticoid receptor agonist, impaired retrieval of long-term memory and if pretreatment with opiate antagonist naloxone blocked their effects on memory retrieval. Young adult male rats were trained in one trial inhibitory avoidance task (1 mA, 1.5 s foot shock). On retention test given 48 hr after training, the latency to re-enter dark compartment of the apparatus was recorded. Thirty min before retention test, the rats were exposed to 10 min of restraint stress in a Plexiglas tube or were injected with dexamethasone (1 mg/kg) with or without prior treatment of naloxone (1 or 2 mg/kg). The results showed that both acute restraint stress and dexamethasone impaired retention performance, and their effects were blocked by naloxone pretreatment. The applied stress increased circulating corticosterone levels as assessed immediately after the retention test, indicating that stress–induced impairment of memory retrieval mediates, in part, by increasing plasma levels of glucocorticoid. These findings further indicate that acute restraint stress and glucocorticoids impair retrieval of long-term memory, and provide evidence for the existence of an interaction between glucocorticoids and opiate system on this process.

Verapamil enhances acute stress or glucocorticoid-induced deficits in retrieval of long-term memory in rats

This study was designed to investigate an interaction between acute restraint stress and corticosterone with verapamil, a blocker of L-type voltage-dependent calcium (VDC) channels on retrieval of long-term memory. Young adult male rats were trained in one trial inhibitory avoidance task (0.5mA, 3s footshock). On retention test given 48h after training, the latency to re-enter dark compartment of the apparatus was recorded. In Experiment 1, verapamil pretreatment (5, 10, or 20mg/kg) enhanced the impairing effects of acute stress (which was applied for 10min in a Plexiglass tube 30min before the retention test) on memory retrieval. The applied stress increased circulating corticosterone levels as assessed immediately after the retention test, indicating that stress-induced impairment of memory retrieval is mediated, in part, by increased plasma levels of glucocorticoids. Verapamil did not change this response. In Experiment 2, pretreatment of an intermediate dose of verapamil also enhanced corticosterone-induced impairment of memory retrieval. In Experiments 3 and 4, acute stress or corticosterone did not change motor activity with or without prior treatment of verapamil, suggesting that stress or glucocorticoid-induced impairment of memory retrieval is not due to any gross disturbances in motor performance of animals. These findings indicate that blockade of L-type VDC channels enhances stress or glucocorticoid-induced impairment of memory retrieval, and provide evidence for the existence of an interaction between glucocorticoids and L-type VDC channels on memory retrieval.

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.

Synaptic Remodeling in Hippocampal CA1 Region of Aged Rats Correlates with Better Memory Performance in Passive Avoidance Test

Aging is associated with deficits in long-term declarative memory formation, and wide differences in performance can be observed among aged individuals. The cellular substrates of these deficits and the reasons for such marked individual differences are not yet fully understood. In the present study, morphologic parameters of synapses and synaptic mitochondria in stratum molecolare of CA1 hippocampal region were investigated in aged (26- to 27-month-old) female rats after a single trial inhibitory avoidance task. In this memory protocol animals learn to avoid a dark compartment in which they received a mild, inescapable foot shock. Rats were tested 3 and 6 or 9 hours after the training, divided into good and bad responders according to their performance (retention times above or below 100 seconds, respectively) and immediately sacrificed. The number of synapses and synaptic mitochondria per cubic micrometer of tissue (numeric density), the average area of synapses and volume of synaptic mitochondria, the total area of synapses per cubic micrometer of tissue, the percentage of perforated synapses and the overall volume of mitochondria per cubic micrometer of tissue were evaluated. In the good responder group, the numeric density of synapses and mitochondria was significantly higher and the average mitochondrial volume was significantly smaller 9 hours versus 6 hours after the training. No significant differences were observed among bad responders. Thus, better performances in passive avoidance memory task are correlated with more efficient plastic remodeling of synaptic contacts and mitochondria in hippocampal CA1. Present findings indicate that maintenance of synaptic plastic reactivity during aging is a critical requirement for preserving long-term memory consolidation.

The memory-impairing effects of septal GABA receptor activation involve GABAergic septo-hippocampal projection neurons

Septal infusions of the gamma-aminobutyric acid (GABA)(A) agonist muscimol impair memory, and the effect likely involves the hippocampus. GABA(A) receptors are present on the perikarya of cholinergic and GABAergic septo-hippocampal (SH) projections. The current experiments determined whether GABAergic SH projections are involved in the memory-impairing effects of septal GABA(A) receptor activation. Experiment 1 tested whether combining septal co-infusions of subeffective doses of muscimol with scopolamine, a drug that selectively influences GABA SH projections, would produce memory deficits. Experiment 2 tested whether hippocampal infusions of a GABA(A) receptor antagonist would block the effects of septal muscimol infusions. Fifteen minutes prior to assessing spontaneous alternation (SA) or training in a multiple trial inhibitory avoidance (CMIA) task, male Sprague-Dawley rats were given septal infusions of vehicle, muscimol, scopolamine, or co-infusions of muscimol with scopolamine, or septal infusions of vehicle or muscimol combined with hippocampal infusions of vehicle or bicuculline. Septal co-infusions of muscimol with scopolamine significantly impaired SA and CMIA. Hippocampal bicuculline infusions blocked deficits produced by septal muscimol infusions in SA and attenuated deficits produced in CMIA. Combined, these findings suggest that GABAergic SH projections are involved in the memory-impairing effects of septal GABA receptor activation.

Hippocampal infusions of glucose reverse memory deficits produced by co-infusions of a GABA receptor agonist

Although septal infusions of glucose typically have positive effects on memory, we have shown repeatedly that this treatment exacerbates memory deficits produced by co-infusions of γ-aminobutyric acid (GABA) receptor agonists. The present experiments tested whether this negative interaction between glucose and GABA in the medial septum would be observed in the hippocampus, a brain region where glucose typically has positive effects on memory. Specifically, we determined whether hippocampal infusions of glucose would reverse or exacerbate memory deficits produced by hippocampal co-infusions of the GABA receptor agonist muscimol. Fifteen minutes prior to either assessing spontaneous alternation (SA) or continuous multiple trial inhibitory avoidance (CMIA) training, male Sprague–Dawley-derived rats were given bilateral hippocampal infusions of vehicle (phosphate-buffered saline [PBS], 1 μl/2 min), glucose (33 or 50 nmol), muscimol (0.3 or 0.4 μg, SA or 3 μg, CMIA) or muscimol and glucose combined in one solution. The results indicated that hippocampal infusions of muscimol alone decreased SA scores and CMIA retention latencies. More importantly, hippocampal infusions of glucose, at doses that had no effect when infused alone, attenuated (33 nmol) or reversed (50 nmol) the muscimol-induced memory deficits. Thus, although co-infusions of glucose with muscimol into the medial septum impair memory, the present findings show that an opposite effect is observed in the hippocampus. Collectively, these findings suggest that the memory-impairing interaction between glucose and GABA in the medial septum is not a general property of the brain, but rather is brain region-dependent.

Microinjections of the dopamine D2 receptor antagonist sulpiride into the medial prefrontal cortex attenuate glucocorticoid-induced impairment of long-term memory retrieval in rats

We recently reported that blockade of dopamine (DA) D2 receptors attenuated deficits in long-term memory retrieval induced by a systemic injection of corticosterone, but the anatomical sites of such interaction were not known. In this study, we investigated whether the DA D2 receptors located in the medial prefrontal cortex (mPFC) may play a role in the impairing effects of glucocorticoids on the memory retrieval process. Young adult male rats were trained in a one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On the retention test given 48 h after training, the latency to re-enter the dark compartment and the time spent in light compartment of the apparatus were recorded. Systemically administered corticosterone (1 mg/kg) given to rats 30 min before retention testing impaired their memory retrieval. Bilateral microinjections of the DA D2 receptor antagonist sulpiride (10 or 100 ng/0.5 μl per side) into the mPFC 30 min before corticosterone administration attenuated the glucocorticoid-induced impairment of memory retrieval. Furthermore, applied doses of sulpiride alone were ineffective in modulating memory retrieval. These findings indicate that D2 receptors located in the mPFC play an important role in mediating the impairing effects of glucocorticoids on memory retrieval.

Glucocorticoid-induced impairment of long-term memory retrieval in rats: An interaction with dopamine D2 receptors

This study investigated glucocorticoid–dopaminergic interactions in modulating retrieval of long-term memory in an inhibitory avoidance task. Young adult male rats were trained in one trial inhibitory avoidance task (0.5 mA, 3 s footshock). On the retention test given 48 h after training, the latency to re-enter the dark compartment of the apparatus was recorded. Systemically administered corticosterone (1 or 3 mg/kg) given to rats 30 min before retention testing impaired their memory retrieval, but the lower dose was more effective than the higher one. Administration of the dopamine (DA) D2 receptor antagonist sulpiride (6 or 20 mg/kg) 30 min before corticosterone attenuated the impairing effects of corticosterone (1 mg/kg) on memory retrieval. Administration of the DA D1 receptor antagonist SCH23390 (25 or 50 μg/kg) had no effect on corticosterone-induced impairment of memory retrieval. Further, applied doses of sulpiride or SCH23390 alone were ineffective in modulating memory retrieval. These findings provide evidence for the existence of an interaction between glucocorticoids and DA D2 receptor on memory retrieval process.

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.

Learning twice is different from learning once and from learning more

The rat hippocampus plays a crucial role in the consolidation of a variety of memories, including that for a one trial inhibitory avoidance learning task in which stepping down from a platform is associated with a footshock. Here we show that this is the case regardless of the intensity of the footshock used and hence, of the strength of the learned response. However, additional learning produced by a second training session in this task does not involve the hippocampus but, instead, the striatum. Memory consolidation of the second trial requires glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionate, N-methyl- d-aspartate and metabotropic receptors, activation of signaling pathways, gene expression and protein synthesis in the striatum, as are required in the hippocampus during memory consolidation of the first trial.

The enhancing effects of hippocampal infusions of glucose are not restricted to spatial working memory

Extensive evidence shows that hippocampal infusions of glucose enhance spontaneous alternation (SA) performance or reverse deficits in this task. The current experiments determined whether the enhancing effects of hippocampal infusions of glucose are restricted to spatial working memory. Specifically we tested whether hippocampal infusions of glucose would reverse deficits in an emotional reference memory task (continuous multiple trial inhibitory avoidance [CMIA]) produced by septal infusions of the γ-aminobutyric acid agonist muscimol. Male Sprague–Dawley rats were given septal infusions of vehicle or muscimol (0.15 nmol: SA; 5 nmol: CMIA) combined with hippocampal infusions of vehicle or glucose (50 nmol) 15 min prior to assessing SA or CMIA training. CMIA retention was tested 48 h later. Muscimol infusions decreased percent alternation scores and avoidance retention latencies. Importantly, hippocampal infusions of glucose reversed the deficits produced by the septal muscimol infusions on both tasks. These findings show for the first time that hippocampal glucose infusions also influence emotional memory, indicating that the enhancing effects of glucose generalize to memory tasks that vary in motivational and cognitive demand.

Inhibition of PKC in basolateral amygdala and posterior parietal cortex impairs consolidation of inhibitory avoidance memory

Hippocampal α- and βI/βII protein kinase C (PKC) are crucial for the formation of different types of memory in several species, including that for a one trial inhibitory avoidance (IA) task in rats. Many studies, however, have shown that other brain structures besides the hippocampus, notably the basolateral amygdala (BLA) and posterior parietal cortex (PC) are also necessary for memory consolidation. Here, we examine the role of α- and βI/βII PKC in the BLA and PC on the consolidation of the memory for IA in rats. The selective inhibitor of α- and βI/βII-PKC Gö 6976 and the nonselective PKC inhibitor Gö 7874 were administered into these structures at different times after training at concentrations known to inhibit PKC and to produce retrograde amnesia when given into the hippocampus. Gö 7874 blocked consolidation of IA memory when infused into BLA immediately and 30 min or into PC 180 to 360 min posttraining. Gö 6976 caused amnesia when given into the BLA also immediately or 30 min posttraining but in the PC hindered memory retention only when infused 270 and 360 min after the training session. Our data indicate that α- and βI/βII-PKC are critical for consolidation of IA memory shortly after training in BLA and that, first other isoforms and subsequently the α- and βI/βII PKC are required 3 or more hours after training in the PC. The findings on BLA are similar to those previously reported in the hippocampus, but those on PC suggest an entirely different molecular dynamics for memory formation in that area.

Participation of hippocampal nicotinic receptors in acquisition, consolidation and retrieval of memory for one trial inhibitory avoidance in rats

Participation of hippocampal nicotinic receptors in acquisition, consolidation and retrieval of memory for one trial inhibitory avoidance in rats