Corticosteroids

Glucocorticoid hormones, released from the adrenal glands, easily access the brain where they can affect neural structure and function through the binding to two types of intracellular receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Secretion of these steroids is activated by exposure to stressful situations, and growing evidence indicates that they can interact with the neurobiological mechanisms subserving memory formation. After a brief description of...

Conclusion

We have reviewed strong evidence that K+ channel modulation influences neuronal spiking and or synaptic transmission and appears to contribute to memory formation (and maybe even retrieval). Considering the results from different model organisms, continuities and changes among them are apparent. Conditioning in two species of mollusc leads to prolonged action potentials. The affected K+ currents are not identical in each case, perhaps a matter of different circuits. In both species,...

Ligand Gated Ion Channel

The 5-HT3 receptor is the only ligand-gated ion channel among the 5-HT receptors. Inactivation of 5-HT3 receptors has been found to increase the frequency of the hippocam-pal theta rhythm and the magnitude and duration of long-term potentiation (LTP) in the CA1 of the hippocampus of freely moving rats.121 These neurophysiological effects have been correlated with improved retention in both spatial and olfactory memory tasks, behaviors which require the integrity of the hippocampus.121 Systemic...

Abbreviations

acid acid 11-HSD 11beta-Hydroxysteroid dehydrogenase acid acid ibuprofen acid ACE angiotensin converting enzyme acid ACTH adrenocorticotropic hormone acid acid receptor AP5 2-amino-5-phosphonovaleric acid Arc activity-regulated cytoskeleton associated protein BDNF brain-derived neurotrophic factor BLA basolateral nucleus of the amygdala BOC tert-butoxycarbonyloxiimino protective group CaMk calmodulin-calcium dependent kinase protein kinase CaMK-II calcium-calmodulin dependent kinase-type II...

Adenosine and Purines

Nikbakht and E. Martin O'Kane Abstract Adenosine can act on four subtypes of receptor, of which the Ai and A2A subtypes have received the most attention experimentally. The Ai receptors are primarily inhibitory by depressing transmitter release or causing hyperpolarisation, while the A2A receptors often cause overall excitation by direct depolarisation or the facilitation of transmitter release. Activation of these receptors can also modulate neuronal sensitivity to...

Adenylyl Cyclases

Nicole Mons and Jean-Louis Guillou Abstract Although a number of signal transduction pathways have been implicated in short- and long-term adaptative changes in neuronal plasticity and memory formation, there is increasing evidence that cross-talk between the cAMP- and Ca2+-regulatory pathways may play a pivotal role in learning and memory processes. The fact that adenylyl cyclases (AC), in both invertebrates and mammals, are potentially subject to a wide range of influences has given rise to...

Alzheimers Disease

Abnormal Ca2+ homeostasis characterizes pathophysiology ofAlzheimer's disease (AD). For instance, in AD fibroblasts, bombesin- and bradykinin-induced Ca2+ release (through IP3Rs) is greatly enhanced, compared with those from control groups.55'61 The Ca2+-mediated acetylcholine release from rat hippocampal slice is potently and acutely inhibited by low concentration (10-8 M) of P-amyloid.64 P-Amyloid (AP) causes the death of cortical neurons at micromolar concentrations38 and can directly form...

Anatomy of Brain Cholinergic Pathways

Muscarinic acetylcholine receptors (mAChRs) are the targets of ACh released from the cholinergic nerve endings and in some cases, are located on cholinergic neurons and nerve endings (autoreceptors). For this reason, a short description of the brain cholinergic system is deemed useful.The central cholinergic system was characterized in the eighties using an anti-choline acetyltransferase (ChAT) antibody99 and it was divided into 10 relatively well defined populations of cholinergic neurons...

Animal and Human Amnesia

The Cholinergic Hypothesis Revisited Robert Jaffard and Aline Marighetto Identifying Memory Dysfunction The net effect of an experimentally-induced or naturally occurring alteration in learning and memory is generally determined by the type of neurological dysfunction (from focal lesions to gene expression) and or the nature of the learning task. Accordingly, memory systems are defined as distinct, but interactive, psychological and biological entities that still need specification. Within this...

Ca2 Influx

The ultimate Ca2+ source for neurons exits outside the neurons. Entry of Ca2+ across the plasma membrane is known to be important in generating neuronal Ca2+ signals, resulting in membrane depolarization and an increased Ca2+ c. Ca2+ channel expression at the cell surface is regulated by intracellular signaling molecules.13 The latter leads to activation of Ca2+-dependent intracellular signal cascades. There is a large gradient of Ca2+ concentration across the plasma membrane extracellular Ca2+...

CaMKII Synaptic Plasticity and Memory Processing

Over the last decades a multidisciplinary effort has been made in the search of the molecular and cellular mechanisms responsible for learning and memory. Most of these studies have utilised as a working hypothesis that postulated by Donald Hebb in 1949 which proposes that a given synapse would be strengthened when the pre and postsynaptic neurons were coinciden-tally activated. Today it is an almost universally accepted hypothesis that the storage of new information under the form of long term...

CaMkiv A New and Important Player in the Plasticity Team

Translocation of CaMKII into the nucleus is thought to be regulated by the phosphorylation of a Ser residue adjacent to the NLS sequence in the nuclear-targeted isoforms. The finding that both CaMKI and CaMKIV are able to phosphorylate that site and hinder the accessibility of CaMKII to the nucleus shows the existence of complicated interrelation mechanisms among the different members of the Ca2+ CaM-dependent kinases family.36 As it happens with CaMKII, both CaMKI and CaMKIV are able to bind...

Cannabinoid Receptor Ligands

Endogenous cannabinoid receptor ligands (endocannabinoids) such as anandamide and 2-arachidonoyl glycerol have been isolated20,70 and are able to bind and activate the cloned cannabinoid receptors. A common property of these endocannabinoids, sometimes referred to as eicosanoids, is that they are chemical derivatives of the polyunsaturated fatty acid, arachi-donic acid. They serve as neurotransmitters neuromodulators, are not stored in vesicles but instead are synthesised on demand and released...

Cannabinoid Receptors Modulate Memory Formation

Most of the animal research summarised below has been guided by work on human subjects, for which disruption of short-term memory is a widely acknowledged effect of marijuana or A9THC.11-13'24,29'72,95 Direct effects on memory storage, however, have not been found.3'24 Interestingly, marijuana increased cerebral blood flow predominantly in paralimbic regions of the frontal lobes and the cerebellum, but reduced blood flow in the temporal lobe. 2 Such hypoactivity may be the neural basis of...

Cell Adhesion Molecules

The molecular cascade of events associated with hippocampal processing of information for long-term storage is a time-limited event. Learning sets in motion neural processes that continue to evolve after training, a phenomenon known as consolidation. The consolidation process has been proposed to involve the translation of neural activity into enduring synaptic change by a cascade of sequential molecular steps involving gene induction, increased protein synthesis and synaptic growth mediated,...

CNS Distribution of the Muscarinic Receptors

While a great diversity of behavioral, physiological and biochemical effects is mediated by mAChRs, the identities of the molecular subtypes responsible for any given neuronal function remain elusive. The complex pharmacology of the mAChR subtypes, together with the lack of drugs with high selectivity has made it difficult to determine the individual roles of m1-m5 receptors in the brain. Identification of the mAChR subtypes in the brain has been accomplished using in situ hybridization to...

Cognitive Alteration Induced by Lesions in the Cholinergic Pathways

The prerequisite of lesion studies is the selectivity of the lesion. In order to investigate their role in learning and memory, the lesions must damage only the cholinergic neurons, a condition which is not easily obtained. The first difficulty is represented by the anatomy of the cholin-ergic system since the basal forebrain cholinergic neurons are not clustered together in a well localized nucleus that can be lesioned easily.22 For many years the second difficulty was the tool for making the...

Cognitive Alterations Induced by the Blockade of Muscarinic Receptors

The nonselective muscarinic antagonist scopolamine has been extensively used to study the cognitive alterations induced by the blockade of muscarinic receptors.112 The interpretation of the pharmacological data is not straightforward, as scopolamine blocks postsynaptic receptors as well as presynaptic autoreceptors, this latter effect being responsible for an increase in ACh.197 Scopolamine administered to human subjects impairs rapid information processing209 and encoding of new memories in...

Cognitive Processes Associated with Changes in Cholinergic Activity

The development of the in vivo microdialysis technique191 coupled to sensitive analytical systems for the quantification of ACh levels in the nanomolar range has made it feasible to correlate changes in ACh extracellular levels in the brain with cognitive processes in the animal. Using this approach, it has been possible to study the behaviorally-induced activation of the cholinergic system ascending from the NB to the cortex, from the septum to the hippocampus or in other structures, during...

Conclusions

In summary, the aforementioned behavioural data seem to provide strong evidence for a role of cannabinoids in learning and formation of different forms of memory. However, it could be argued that because systemic infusion of A9THC or other synthetic cannabinoid receptor agonists has numerous unspecific effects, hard proof is difficult to obtain and many studies may be flawed by the overshadowing effects of CB1 activation-induced changes in activity or reward rather than learning. While this may...

Contents

Preface Ca2+ Neurotransmitter Modulation of Channel Signal Transduction Cascades Jeffrey Vernon and Karl Peter Giese How Can K+ Channels Contribute to Learning and Memory 22 Section 2. Principle Neurotransmitters 2.1. Glutamate Gernot Riedel, Jacques Micheau and Bettina Platt Glutamate Receptor Function in Learning and Memory 2.2. y-Amino-Butyric Acid Claudio Castellano, Vincenzo Cestari and Alessandro Ciamei GABAergic Drugs and Memory Formation Peripheral GABAergic Drugs and Memory...

Creb

Josselyn Abstract The cAMP Responsive Element Binding Protein (CREB) is an activity regulated transcription factor that modulates the transcription of genes with cAMP responsive elements (CRE) located in their promoter regions. A variety of signaling pathways converge to phosphorylate CREB at Ser133 and induce transcription. Here, we review the key features of CREB-dependent transcription and evaluate evidence suggesting that CREB plays a key role in different...

DA Receptors and Cognition

When discussing DA receptors and locomotor activity we already pointed at the role of DA receptors in cognitive performance. This subject has been intensively studied by Goldman-Rakic, Arnsten, and co-workers in the nineties, using both monkeys and rats as experimental subjects. In a study with rhesus monkeys, Arnsten et al5 have provided compelling evidence that cognitive performance depends on DA D1 receptor mechanisms. In this study both young and aged monkeys were used. In aged primates...

DA Receptors and Eating and Drinking

Besides their effects on locomotor activity and reward-related processes, dopaminergic drugs are also known to affect eating and drinking. One of the first studies was conducted by Zigmond et al68 An increased DA release (achieved by d-amphetamine) reduced food intake. This effect was attenuated by DA receptor antagonists (haloperidol or spiroperidol). However at higher doses such DA receptor antagonists also reduced food intake. The interesting conclusion of the authors is that there is an...

Dopaminergic Depletions and Cognitive Impairments

Ever since the availability of drugs that specifically destroy dopaminergic cells and fibres, the technique of local DA depletion has been a powerful tool in examining the contribution of dopaminergic systems in behavioural performance. The most widely used drug in such studies is 6-OHDA (6-hydroxy-dopamine) that will destroy dopaminergic cells and fibres, while leaving postsynaptic terminals intact. Unfortunately, 6-OHDA is not specific for dopamine but will also damage noradrenergic cells and...

Epilogue

In this review we have considered the role of DA receptors in cognitive processes. There are different dopaminergic systems in the mammalian brain and different subtypes of DA receptors. It is especially the mesocortical dopaminergic system innervating the PFC and other cortical areas which is involved in cognitive processes. The actions of DA on these processes are prominently modulated by D1 receptors. Findings from different sources have led to the inverted U-shape model (Desimone23). There...

Functional Studies Using a Central Approach

Studies using systemic administration of dopaminergic drugs and examining concomitant behavioural alterations do not directly reveal which brain areas are important for the performance of tasks under investigation. However, sometimes deductions can be made. When the task is sensitive for damage of a particular brain area, and when performance is affected by selective dopaminergic drugs, it can be assumed that the drugs exert their effect in that brain area. This can be exemplified by the study...

GABAergic Drugs and Memory Formation Administrations into Brain Structures

The possibility that GABAergic agonists and antagonists exert their effects on memory as a consequence of specific actions on central GABAergic receptors has been examined by a number of studies. The first brain structure considered has been the amygdala. It is known that retention can be modulated by posttraining intra-amygdala injections of drugs affecting several neurotrans- Figure 3. Effect of immediately posttraining intra-amygdala administrations of baclofen on retention of a one-trial...

GABAergic Drugs and Memory Genotype Dependent Effects

Studies carried out with the inbred strains of mice C57BL 6 (C57) and DBA 2 (DBA) have shown that the genetic makeup plays an important role in modulating responses to drug administration. As concerns memory processes, strain-dependent effects have been observed, in C57 and DBA mice, following posttraining injections of a number of drugs, such as opioid agonists and antagonists, corticosterone, nicotine and dopaminergic agents. For a review see reference 20. Experiments have recently been...

Hippocampal Involvement in Learning

In the early 1950s, numerous patients with intractable epileptic seizures underwent experimental surgeries involving removal of one or both temporal lobes. The surgeries appeared at first glance to be successful, as removal had the desired beneficial effect of ameliorating the seizures. However, in patients who had unknown temporal lesions in the opposite brain hemisphere or who underwent bilateral temporal ablations, the surgery had tragic results. One such patient, H.M., displayed severe...

HT Receptors and Linkage to Second Messenger Signaling Pathways

Among the fourteen different 5-HT receptor types or subtypes, only 5-HT3 is a transmitter-gated cation channel, all other 5-HT receptors are linked to guanine nucleotide-binding proteins (G proteins) and members of the seven transmembrane (7TM) domain receptors. 5 The class of 5-HT1 receptor is coupled to Gi o, the 5-HT2 to Gq 11, the 5-HT4 6 7 to Gs (Fig. 2 for reviews see Hoyer and Martin,64 Barnes and Sharp11). The Gi o and Gs linkages decrease and increase adenylyl cyclase (AC) activity,...

Intracerebral Infusion of Dopaminergic Drugs and Cognitive Processes

An important progress in the search for dopaminergic involvement in cognitive processes has been the development of the technique of chronic intracerebral cannulae providing the possibility of infusing dopaminergic drugs into small, well-defined areas of the brain. The areas targeted in this manner have been especially the striatal and prefrontal cortical areas. We will focus on the prefrontal cortical areas. We will first review studies using local administration of dopaminergic drugs...

Introduction

It has been known for centuries that the berries, roots and leaves of Atropa belladonna and other plants of the Solanaceous family cause disturbances in memory and orientation and, increasing the doses, cause hallucination and delirium.71 For a long time, the latter effects attracted more attention that the subtle effects on memory.113 However, the retrograde amnesia following atropine intoxication was noted and reported also in the past. According to Muccioli,13 patients poisoned with atropine...

Jan PC de Bruin Abstract

Since the discovery that dopamine occurs in the cerebral cortex and functions as a transmitter a large number of studies has been conducted to examine its precise functions. It was found that administering dopaminergic drugs, either stimulating or inhibiting dopamine receptors, affected various modes of behaviour, including locomotor activity, eating and drinking, reward-related processes, and cognition. This chapter is especially concerned with the role of dopamine receptors in cognitive...

Joyce Besheer and Rick A Bevins Abstract

The nicotinic cholinergic system has been widely implicated in mediating learning and or memory processes in human and nonhuman animals. This chapter highlights various areas of basic research in which stimulation or blockade of nicotinic acetylcholine receptors (nAChRs) has been shown to affect an animal's performance in a variety of tasks thought to measure learning and memory. For example, under certain conditions, stimulation of nAChRs by nicotine (or other nAChRs agonists) can enhance...

Kinases and Phosphatases in Chick Memory Formation

For the past three decades Ng, Gibbs, and their colleagues have investigated memory formation in groups of day-old-chicks trained using a single-trial PAL task in which chicks learn to avoid a red coloured bead which has been coated during a single, ten second training trial, with an aversive chemical, methylanthranilate (reviewed in ref. 144). By testing groups of chicks at precise times relative to learning, it has been possible to document the temporal characteristics of the memory trace...

Learning Induced Synaptogenesis and Structural Synaptic Remodeling

Berry and Olga T. Ganeshina Abstract This chapter analyzes the results of quantitative electron microscopic studies of the vertebrate brain aimed at the elucidation of changes in synaptic unltrastructure that may underlie learning and memory. It has been reported that behavioral learning promotes new synapse formation, including both a net synaptogenesis, which causes a net gain in synapse number, and a specific synaptogenesis. The latter either accompanies a...

Memory Studies with Adrenoceptor Agonists and Antagonists in Chicks

We have systematically investigated the roles of adrenoceptors in the action of noradrena-line in a one trial learning task (discriminated avoidance learning) in the young chick, where the chick discriminates between red and blue beads. The chick at one to two days of age has a number of distinct advantages over rodents in the study of memory, including limited development of the blood brain barrier, the ability to learn about coloured beads in one short trial without any prior knowledge of...

Nitric Oxide

Ltp And Ltd Nmda

Kiyofumi Yamada and Toshitaka Nabeshima Abstract Among three isoforms of nitric oxide (NO) synthase, both neuronal and endothelial NO synthases may play an important role in learning and memory. NO production in the brain increases, in an activity-dependent manner, following an increase in intracellular Ca2+ levels. Electrophysiological studies revealed that the NO cGMP pathway plays an important role as an intercellular messenger in the long-term potentiation and long-term depression, which is...

Phospholipases and Oxidases

Memory formation is dependent on a series of biochemical cascades that alter synaptic transmission and neuronal activity. Phospholipases are key enzymes in these cascades that produce second messengers, which interact with a host of target systems, such as transmitter uptake systems, transmitter release, and intracellular calcium stores. One of the main second messengers is arachidonic acid, which also acts as a substrate for lipoxygenases and cyclooxygenases. These enzymes metabolise...

Posterior Pituitary Peptides Vasopressin Oxytocin

Vasopressin exerts a long-term facilitating effect on learning and memory processes, which can be clearly demonstrated in aversive-conditioning. The influence of vasopressin is time-dependent, i.e., the effectiveness of neuropeptide treatment depends on the time interval between the learning or retention trial and the treatment. Vasopressin and related peptides facilitate consolidation as well as retrieval processes. These neuropeptides also prevent and reverse retrograde amnesia induced by...

Protein Kinase A

Vianna and Ivan Izquierdo Abstract Memories are believed to rely upon enduring morphologic and functional changes at synapses activated by learning events. Experiments carried out in the past two decades have indicated that several cellular mechanisms need to be activated in order for the synaptic changes to take place. Among these general cellular mechanisms, enzymatic cascades including the cAMP-dependent protein kinase (protein kinase A, PKA) signaling pathway in CA1 region of...

Protein Phosphatases in Rodent Learning and Memory

Pharmacological studies examining phosphatase involvement in memory formation in rodents have emerged only recently. One of these found that rats infused with OA for several weeks developed learning difficulties.4 The rats also demonstrated gross morphological changes, however, making it difficult to determine whether phosphatase inhibition was responsible for the learning deficits or whether these deficits may have reflected a secondary problem.136 In another study, microinjection of OA into...

Protein Phosphorylation What Is It and Why Is It Significant

The cells that make up biological organisms comprise numerous components. Many are proteins, the sequence of which is encoded genetically. Proteins carry small, localized, electrostatic charges that force each molecule to adopt a three-dimensional configuration specific for that protein. This configuration determines its function. Several mechanisms have evolved by which the configuration and function of proteins can be altered. Some are irreversible, resulting in permanent structural and...

Protein Synthesis I Pharmacology

Oliver Stork and Hans Welz Abstract The formation of long-lasting memory traces depends on the de novo synthesis of proteins. For more than 30 years substantial experimental evidence has been collected in species ranging from insects to mammals, in support of this hypothesis. A pharmacological approach to investigate the dependence of long-term memory formation on de novo protein synthesis is to administer drugs that prevent protein synthesis on the transcriptional or translational level. When...

Protein Synthesis II New Proteins

The role of protein synthesis in long-term memory formation is still an area of intense scientific interest, which encompasses the study of mechanisms involved in gene expression and molecular mechanisms underlying synaptic plasticity. A number of low molecular weight compounds have been used to inhibit or enhance this fundamental cellular process. The pivotal role of protein synthesis in long-term memory formation suggest yet again that an understanding of how protein synthesis can be...

Receptors that Stimulate Adenylyl Cyclase

The 5-HT4 receptor is present in the frontal cortex and the hippocampus (Fig. 3). 5-HT4 receptor agonists stimulate adenylyl cyclase, thereby increasing cAMP levels and producing a decreased after-hyperpolarization that may increase neuronal excitability and neurotransmitter release.41 Stimulation of 5-HT4 receptors by specific agonists selectively facilitates basal ACh release in the frontal cortex of rats, but not in the striatum,41 and increases the extracellular level of 5-HT in the...

Receptors that Stimulate Phospholipase C

The 5-HT2A and 5-HT2C receptors both stimulate phospholipase C and show a close structural homology. So far, there are no ligands truly selective for each of these receptor subtypes, and few studies are available on the effects of 5-HT2 receptors in learning and memory. They are present in high concentrations in cortical areas and are thought to mediate more attentional than memory processes.24 Activation of 5-HT2A 2C receptors induces a facilita-tory effect on cholinergic release in the rat...

References

Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory. Cell 1997 88 615-626. 2. Abeliovich A, Chen C, Goda Y et al. Modified hippocampal long-term potentiation in PKCg-mutant mice. Cell 1993 75 1253-1262. 3. Abeliovich A, Paylor R, Chen C et al. PKCg mutant mice exhibit mild deficits in spatial and contextual learning. Cell 1993 75 1263-1271. 4. Adams JP, Anderson AE, Varga AW et al. The A-type potassium...

Role of 5HT in Memory Global Strategies

Metabolism Neurotransmitter

Serotonergic projections from the raphe nuclei, where cell bodies are concentrated, are widespread and terminate in brain structures thought to underly memory processes such as the hippocampus, the prefrontal cortex, cortical associative areas, basal ganglia, or thalamus. The projections to the frontal cortex predominantly originate in the dorsal raphe nucleus (DRN), whereas the projections to the hippocampus arise from the median raphe nucleus (MRN). The DRN regulates the excitability of...

Signal Transduction Cascades

One critical role of Ca2+ in neuronal signaling is to couple electrical excitation to the activation of intracellular enzymes, such as various tyrosine protein kinases,128'130 and signal trans-duction cascades (Fig. 1). Ca2+ regulates a wide variety of biological functions through binding to proteins, so to confine it neatly to one predominant role in mediating effects of signal transduction on synaptic plasticity may be unrealistic. Most Ca2+-binding proteins can be grouped into families with...

Signal Transduction Pathways of PAdrenoceptors

P-ARs are coupled by Gs to adenylate cyclase and produce alterations in cellular activity by raising intracellular levels of cyclic AMP (Fig. 3). Pharmacologically, the classical P-ARs have been defined as receptors at which (-)-isoprenaline acts as an agonist and (-)-propranolol as an antagonist. In addition to the classical P1- and P2-ARs there is a third subtype, the P3-AR, Figure 1. Signal transduction pathways for aj-adrenocceptors. Gq jj couples aj-adrenenoceptor to PIP2 (phosphatidyl...

Spatial Learning

Many thoughtfully developed spatial testing procedures are available to date and the most popular ones are the water maze, the 8-arm radial maze and T- or Y-mazes. These paradigms allow for spatial reference and or working memory to be assessed and there are also some Table 2. Effects of glutamate receptor blockade on spatial learning and memory formation i.c.v. (minipump), i.HC, i.IC, s.c., i.p. (postnatal d8- d19), i.v. N AP5,CPP, MK801, ketamine 7Cl-kynurenate 5,11,53,68,76, 76,78,83,125,...

Spatial Learning Water Maze

Training in an open water-filled tank containing a submerged platform is a popular learning paradigm tackling spatial and thus hippocampal-dependent memory.75 Animals learn to find the submerged platform in the opaque water in relation to distal cues and reduce their latency to swim and climb onto it over days. Despite its long tradition as a behavioural test, reports on the effects of cannabinoids are relatively recent. The initial report by Ferrari and colleagues28 revealed evidence for...

T

MR antagonist altered pecking pattern diminished avoidance GR antagonist no effect diminished avoidance Figure 3. Schematic representation of the one-trial passive avoidance task in the day-old chick and the effects of the administration of mineralocorticoid (MR) and glucocorticoid (GR) receptor antagonists on memory for this task. On the training session, due to their innate tendency to peak salient objects in their environment, chicks peck at a bright bead which has been coated in an aversive...

T t

Basolateral nucleus Inhibition of glucocortrcoid-induced Figure 5. Role of amygdala nuclei in the memory-facilitating effect of glucocorticoids. Cartoon showing neural circuits involved in the communication among different amygdala nuclei. When the central nucleus is lesioned in rats before being exposed to a training session in the passive avoidance task, the enhancement ofmemory induced by a posttraining glucocorticoid injection is preserved. However, when it is the basolateral nucleus which...

Taskadmin doseAcquisition Learning Consolidation Retrieval Observations

Repeated acquisition procedure with light-related keypressing i.c.v. intracerebroventricularly i.p. intraperitoneally p.o. per orally s.c. subcutaneous working memory version of the task, and were also insensitive to A9THC, WIN55,212-2 or methanandamide treatment, which disrupted working memory in wild-type littermates in a SRl4l716A-sensitive manner.

Why Phosphorylation Might Be Critical for Memory Formation

The demonstrated involvement of phosphorylative regulation in almost every facet of cell functioning provides justification for examining the contributions made by this process to memory formation. One of the difficulties inherent with research in this area, however, lies in distinguishing brain processes that play a direct role in retaining information from those that play a less direct, but equally critical, role, perhaps being necessary for general cell functioning, without which memory...

Immediate Early Genes

Immediate Early Genes Iegs

Jeffrey Greenwood, Pauline Curtis, Barbara Logan, Wickliffe Abraham and Mike Dragunow How long-term memories are formed in the brain is one of the principal targets of contemporary neuroscience research. This work is important from a fundamental perspective, because memory is a vital component of virtually all cognitive activity. It is also important from a clinical perspective since the early and most dramatic symptoms of Alzheimer's disease (AD) are an impairment of memory formation. Diseases...

Muscarinic Receptors in Aging and Alzheimers Disease

Whether or not the mild cognitive deficits associated with aging or the severe memory loss in AD depend, at least partly, on the loss of muscarinic receptors or change in their function is a controversial topic. Age-related loss of muscarinic receptors in rat neocortex and hippocampus is still a matter of debate, with the majority of the studies reporting no changes, and a few reporting a decrease or even an increase in binding sites.44,196 In a recent PET study using N- 11C methyl-4-piperidyl...

Table 3 Effects of opioid receptor ligands on the various learning and memory tasks

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Olfactory and Gustatory Memory Paradigms

There are various behavioural models to assess olfactory memory, for example using a social recognition task. Adult animals meet a juvenile conspecific and explore him her via anogenital sniffing for say 5 mins. Reexposure to the same (familiar) juvenile after minutes to1 hour will lead to reduced anogenital sniffing reflecting recognition memory. If exposed to a different juvenile, however, anogenital sniffing will be high. Social recognition memory is affected by the CB1 receptor agonist...

Downstream Effectors of the CaMKII Cascade

What are the consequences of CaMKII translocation How does the activation of this kinase contribute to the establishment of LTP and in which way is this contribution related to the formation of new memories CaMKII phosphorylates several PSD-associated proteins, including PSD-95, a and P tubulin, the GTPase dynamin, the type IV intermediate filament protein a-internexin and cAMP phosphodiesterase,120 although the functional consequences of most of these phosphorylations are not known. Despite...

Brain Gut Peptides CCK Neuropeptide Y Galanin

Cholecystokinin (CCK) is a peptide originally discovered in the gastorintestinal tract but also found in high density in the mammalian brain. The C-terminal sulphated octapeptide fragment of cholecystokinin (CCK-8) constitutes one of the major neuropeptides in the brain CCK-8 has been shown to be involved in numerous physiological functions such as feeding behavior, central respiratory control and cardiovascular tonus, vigilance states, memory processes, nociception, emotional and motivational...

Receptors that Inhibit Adenylyl Cyclase

The 5-HT1A receptor is characterized by its high concentration in the hippocampus (Fig. 3), as well as in the raphe, where autoreceptors are also likely to exert an indirect influence on cognitive functions. This receptor subtype interacts with other neurotransmitter systems, such as the cholinergic, glutamatergic, GABAergic ones.52 8-OH-DPAT, a specific 5-HT1A agonist, dose-dependently impairs the retention of a well-learned maze, as well as acquisition of a novel configuration of the maze.67...

How Can K Channels Contribute to Learning and Memory

It is generally accepted that synaptic inputs trigger L& M mechanisms. Synaptic receptors activate signalling pathways resulting in the phosphorylation of proteins such as ion channels, modulating their properties. Phosphorylation is a recognised mechanism of channel modula-tion74 and the data discussed in this paper show that kinases are implicated in L& M in both invertebrates and vertebrates. K+ channels may contribute to L& M in three ways, as shown by Figure 2. (1) Modulation of...

Pp2a

Initial studies employed the drugs Okadaic Acid (OA) and Calyculin A (CalA), agents widely acknowledged to be specific and selective phosphatase inhibitors.54 Both drugs disrupted retention from two different time points depending on the concentration of drug administered and the time relative to training at which administration took place.17,224 At concentrations of OA that might be expected to selectively inhibit PP2A (0.5 nM per hemisphere), bilateral intracranial administration of either...

Eph Receptors and Their Ephrin Ligands in Neural Plasticity

Spontaneous Alternation Maze

Eph receptor tyrosine kinases are largely known for their involvement in brain development. But, as these receptors are also expressed in the adult, their possible role in the mature nervous system has begun to be explored. Emerging evidence for the involvement of Eph receptors in synaptic plasticity, learning and memory is discussed in this chapter. It is forecast that the actions of Eph receptors in the adult brain will attract significant attention, and research into their roles will have...