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Muscarinic acetylcholine receptors in the hippocampus, neocortex and amygdala: a review of immunocytochemical localization in relation to learning and memory.

Immunocytochemical mapping studies employing the extensively used monoclonal anti-muscarinic acetylcholine receptor (mAChR) antibody M35 are reviewed. We focus on three neuronal muscarinic cholinoceptive substrates, which are target regions of the cholinergic basal forebrain system intimately involved in cognitive functions: the hippocampus; neocortex; and amygdala. The distribution and neurochemistry of mAChR-immunoreactive cells as well as behaviorally induced alterations in mAChR-immunoreactivity (ir) are described in detail. M35+ neurons are viewed as cells actively engaged in neuronal functions in which the cholinergic system is typically involved. Phosphorylation and subsequent internalization of muscarinic receptors determine the immunocytochemical outcome, and hence M35 as a tool to visualize muscarinic receptors is less suitable for detection of the entire pool of mAChRs in the central nervous system (CNS). Instead, M35 is sensitive to and capable of detecting alterations in the physiological condition of muscarinic receptors. Therefore, M35 is an excellent tool to localize alterations in cellular cholinoceptivity in the CNS. M35-ir is not only determined by acetylcholine (ACh), but by any substance that changes the phosphorylation/internalization state of the mAChR. An important consequence of this proposition is that other neurotransmitters than ACh (especially glutamate) can regulate M35-ir and the cholinoceptive state of a neuron, and hence the functional properties of a neuron. One of the primary objectives of this review is to provide a synthesis of our data and literature data on mAChR-ir. We propose a hypothesis for the role of muscarinic receptors in learning and memory in terms of modulation between learning and recall states of brain areas at the postsynaptic level as studied by way of immunocytochemistry employing the monoclonal antibody M35.

Age Factors↗

Behavioral differences between male and female rats: effects of gonadal hormones on learning and memory.

The organizational, activational and reorganizational effects of gonadal hormones have been extensively investigated with respect to sexual, aggressive and maternal behavior. It has thus been established that manipulations of gonadal hormones during critical periods in development functionally affect reproductive behavior. The effects of gonadal hormones on nonreproductive behavior are not immediately obvious because of the fact that the behavioral effects of gonadal hormones on learning and memory have been investigated in a large number of unrelated experimental procedures. The present paper provides an organized overview of these different experimental procedures, summarizes the most important findings and discusses some of the variables which determine the effects of manipulations in gonadal hormones on learning and memory in male and female rats.

Animals↗

Learning and memory in adolescent psychiatric inpatients with major depression: a normative study of the California Verbal Learning Test.

Depressed adults have deficits in memory functions, especially on demanding tasks, but few studies of depressed adolescents have been published. In order to examine the extent of memory impairment and its diagnostic specificity, adolescent inpatients with DSM-III-R diagnoses of Major Depression (n = 56), Conduct Disorder (n = 42), or mixed Depression and Conduct Disorder (n = 22) were tested on the California Verbal Learning Test (CVLT) and compared to each other, to CVLT norms, and to previously published CVLT norms for adults with Major Depression. Adolescents with Major Depression performed below normative standards on all aspects of the CVLT, but did not have a specific profile of memory impairments that was different from the two comparison samples. Relative to norms for adult patients with Major Depression, adolescent females under performed across all CVLT measures, but males did not differ from adults Depression in adolescence is not associated with specific memory impairments, but adolescent females with depression may have more severe deficits than depressed adults.

Journal Article↗

Prenatal morphine exposure differentially alters learning and memory in male and female rats.

The present study tested the hypothesis that exposure to morphine on prenatal days 11-18 impairs performance on tasks requiring learning and memory in adult male and female rats. In Experiment 1, a symmetrical maze was used to measure learning. In Experiment 2, an eight-arm radial maze was used to assess working spatial memory. The results of Experiment 1 demonstrated that prenatal morphine exposure reduces the time needed to complete the trials, but does not affect the accuracy of performance in male rats. In contrast, prenatal drug treatment had no effects on either the time or the accuracy of performance in female rats. In Experiment 2, both male and female morphine-exposed rats needed more time to complete regular trials (no delay) than controls; however, morphine exposure in male rats did not affect performance on tasks requiring memory, measured with delay trials, but hindered it in ovariohysterectomized (OVX) female rats. In OVX females, replacement injections of both estrogen and progesterone restored the impairment of performance on delay trials produced by prenatal morphine exposure. Thus, the present study demonstrates that prenatal morphine exposure differentially alters performance of adult male and female rats on tasks requiring learning and spatial memory.

Animals↗

D-cycloserine attenuates scopolamine-induced learning and memory deficits in rats.

The muscarinic antagonist scopolamine (SCOP; 1.0 mg/kg, ip) impaired both the acquisition of a learning task in the Morris water maze (MWM) and choice accuracy in the T-maze reinforced alternation procedure in rats. Acetylcholinesterase inhibitors (AChEIs) have been shown to attenuate these deficits. D-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex, was investigated for its effects on SCOP-induced dementia in the MWM and T-maze paradigms. Combined administration of SCOP and DCS (3.0, 10.0, or 30.0 mg/kg, ip; 30 min pretreat) significantly reversed SCOP-induced deficits in the T-maze as measured by percentage correct choices. In addition, DCS (3.0 or 10.0 mg/kg, ip) significantly attenuated SCOP-induced deficits in the MWM as measured by latency to find the submerged platform. For comparison, the long-acting acetylcholinesterase inhibitor galanthamine (GAL) was tested in the T-maze (1.25, 2.5, or 5.0 mg/kg, ip) and the MWM (2.5 or 5.0 mg/kg, ip). GAL attenuated SCOP-induced deficits in both learning and memory models similar to DCS. These data suggest that the strychnine-insensitive partial glycine agonist, D-cycloserine, may be efficacious in disease states of central cholinergic hypofunction such as Alzheimer's disease.

Animals↗

Impairments in spatial learning and memory: ethanol, allopregnanolone, and the hippocampus.

Acute ethanol administration impairs performance in many cognitive tasks that are dependent on hippocampal function. For example, acute ethanol administration produces dose-dependent impairments in spatial learning. Ethanol also decreases the spatial specificity of hippocampal place cells. Such findings raise the possibility that ethanol affects learning and memory by altering, either directly or indirectly, neuronal activity in the hippocampus and related structures. Acute ethanol administration induces a dose- and time-dependent increase in brain concentration of the neuroactive steroid allopregnanolone. Allopregnanolone is a potent GABAA receptor agonist and produces effects similar to the effects produced by ethanol. Blockade of de novo biosynthesis of allopregnanolone alters many of ethanol's effects including ethanol-induced suppression of spontaneous activity in medial septum/diagonal band of Broca neurons and hippocampal pyramidal neurons. These findings suggest that ethanol-induced increases in allopregnanolone levels might play a central role in the effects of acute ethanol on cognitive processing and hippocampal function. The impact of ethanol on spatial cognitive processing and hippocampal function will be reviewed. In addition, the possibility that ethanol-induced changes in neuroactive steroid levels contribute to the impact of ethanol on spatial learning and hippocampal function will be explored.

Animals↗

Excitatory amino acid antagonists and memory: effect of drugs acting at N-methyl-D-aspartate receptors in learning and memory tasks.

The role of N-methyl-D-aspartate (NMDA) receptors in memory processes was examined using a Y-shaped maze and a step-through passive avoidance task in mice. In the Y-maze, the total number of arm entries, which represents locomotor activity and alternation behaviour, thought to reflect working memory, were measured. Competitive NMDA antagonists, CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylate) and CPP (3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphate), impaired spontaneous alternation at doses which reduced locomotion of mice. N-Methyl-D-aspartate prevented the impairment of alternation and decrease of locomotor activity produced by CGS 19755 and CPP. These results suggest that NMDA-dependent processes are involved in the mechanisms of working memory. In contrast, the non-competitive NMDA antagonist, MK 801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate) dramatically enhanced the total number of arm entries, while reducing alternation behaviour, N-Methyl-D-aspartate had no effect on MK 801-induced enhancement of locomotor activity and impairment of alternation. In the passive avoidance task, mice were trained to avoid entry into the dark compartment. At doses which impaired working memory in the alternation task, CPP, CGS 19755 and MK-801 reduced acquisition, when administered before training. N-Methyl-D-aspartate antagonized the effect of CPP, CGS 19755 and MK-801. Neither CPP nor MK-801 affected retention, when administered immediately after training or before testing retention. N-Methyl-D-aspartate had no effect on retention with high-intensity shock, but facilitated retention with low-intensity shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of Curcuma phaeocaulis on learning and memory and lipid peroxide in mice].

Nine months mice were inoculated and the method of water maze test and lipid peroxide determination to study the effects of extract of Curcuma phaeocaulis Valeton on learning and memory ability and retarding of senescence. Results showed that in water maze test the time for the group with Curcuma phaeocaulis Valeton needed from initial position to the end was significantly shortened compared with old control. The error numbers for the group of Curcuma phaeocaulis Valeton were significantly decreased compared with old control after starting experiment for 18 days and 24 days and for 35 days no significance difference was showed between groups. The levels of brain, liver and red blood cells lipid peroxide in the group with Curcuma phaeocaulis Valeton were considerably lower than old control, hemoglobin content was considerably increased than old control.

Aging↗

Characterization of learning and memory deficits in C57BL/6 mice infected with LP-BM5, a murine model of AIDS.

Mice infected with an immunosuppressive murine leukemia virus mixture, LP-BM5 show a profound immunosuppression described as murine acquired immune deficiency syndrome (AIDS). In the present study, we characterized learning and memory deficits in C57BL/6 mice infected with LP-BM5. Spontaneous alternation behavior in a Y-maze and latent learning (spatial attention) in a water-finding test, as well as spatial reference and reversal learning in a water maze test, were significantly impaired in the mice infected with LP-BM5. These deficits appeared in the absence of any motoric and visual impairment as assessed by open-field, rotarod and visual water maze tests. These results suggest that cognitive functions are impaired in the mice infected with LP-BM5. Furthermore, LP-BM5-infected mice may be useful as a model for the AIDS dementia complex.

AIDS Dementia Complex↗

Learning and memory functions of the Basal Ganglia.

Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.

Animals↗

The brain decade in debate: I. Neurobiology of learning and memory.

This article is a transcription of an electronic symposium in which some active researchers were invited by the Brazilian Society for Neuroscience and Behavior (SBNeC) to discuss the last decade's advances in neurobiology of learning and memory. The way different parts of the brain are recruited during the storage of different kinds of memory (e.g., short-term vs long-term memory, declarative vs procedural memory) and even the property of these divisions were discussed. It was pointed out that the brain does not really store memories, but stores traces of information that are later used to create memories, not always expressing a completely veridical picture of the past experienced reality. To perform this process different parts of the brain act as important nodes of the neural network that encode, store and retrieve the information that will be used to create memories. Some of the brain regions are recognizably active during the activation of short-term working memory (e.g., prefrontal cortex), or the storage of information retrieved as long-term explicit memories (e.g., hippocampus and related cortical areas) or the modulation of the storage of memories related to emotional events (e.g., amygdala). This does not mean that there is a separate neural structure completely supporting the storage of each kind of memory but means that these memories critically depend on the functioning of these neural structures. The current view is that there is no sense in talking about hippocampus-based or amygdala-based memory since this implies that there is a one-to-one correspondence. The present question to be solved is how systems interact in memory. The pertinence of attributing a critical role to cellular processes like synaptic tagging and protein kinase A activation to explain the memory storage processes at the cellular level was also discussed.

Amygdala↗

A critique of the neuroecology of learning and memory.

Recent years have seen the emergence of neuroecology, the study of the neural mechanisms of behaviour guided by functional and evolutionary principles. This research has been of enormous value for our understanding of the evolution of brain- and species-specific behaviour. However, we question the validity of the neuroecological approach when applied to the analysis of learning and memory, given its arbitrary assumption that different 'problems' engage different memory mechanisms. Differences in memory-based performance in 'natural' tasks do not prove differences in memory capacity; similarly, differences in the use of memory in the natural environment do not provide a sound basis for expecting differences in anatomical structures that subserve learning and memory. This critique is illustrated with examples taken from the study of the neurobiology of food storing and song learning in birds.

Journal Article↗

[Serotonin excess in the brain modifies the effect of beta-endorphin and dalargin on the processes of learning and memory].

In experiments on outbred female rats the influence was studied and compared of two representatives of endogenous opioids beta-endorphine and the analogue of leu-enkephalin dalargin on the processes of learning and memory in normal conditions and at the change of functional state of serotoninergic system of the brain. Parallel, the influence was studied of neuropeptides on the content of serotonin (5-OT) and its metabolite--5-oxyindolacetic acid in various areas of the brain in control and at the 5-OT redundancy. Conditioned reflexes (CRs) were used of two-way avoidance and defensive CRs. It has been established that administration of neuropeptides to intact animals influences in different directions the elaboration of the CR of two-way avoidance and maze defensive CR, but also worsens their preservation. Redundancy of 5-OT in the brain modifies behavioural effects of beta-endorphine and dalargin manifested in appearance of new effect and elimination and change of direction of the effects observed in the intact animals. Redundancy of 5-OT in the brain changes metabolic effects of beta-endorphine and particularly of dalargin. The obtained data testify to a dependence of the effects of beta-endorphine and dalargin on the functional state of 5-OT-ergic system.

Animals↗

Learning and memory in nucleus basalis magnocellularis-lesioned rats after transplantation of fetal frontal cortex.

The effect of fetal frontal cortex transplantation on behaviour performance was examined in adult male Wistar rats with lesions of the nucleus basalis magnocellularis (NBM). Compared to intact and sham-operated controls, the rats tested ten or twenty days after bilateral electrolytic lesions of NBM exhibited the significant learning and memory impairments (acquisition and performance of two-way active avoidance) whereas spontaneous motor activity was not significantly altered. The animals which received allotransplants of fetal frontal cortex (from 18-day gestational rat fetuses) into NBM, two ("early" transplantation-NBM-ET) or ten ("delayed" transplantation-NBM-DT) days after lesioning, respectively, manifested the complete amelioration of noticed impairments when tested ten days after transplantation procedure. Corresponding sham-transplants groups (NBM-SET and NBM-SDT) showed only slightly improvement of acquisition but not performance of two-way active avoidance. The ability of the transplants to restore learning and memory in the NBM lesioned rats suggests that graft of fetal frontal cortex can functionally influence neuronal activity of the lesioned host brain.

Animals↗

Ionic mechanism of acupuncture on improvement of learning and memory in aged mammals.

Memory impairment is one of the most frustrating problems for older people. Several acupoints were used for the treatment of memory loss in old rats, and the elemental mechanism of acupuncture therapy was studied with Inductively Coupled Plasma Spectroscopy. The result indicates that acupuncture improves learning and memory ability significantly in aged animals when compared with controls. This study demonstrated that elevations of eight essential elements (B, Ca, Cu, Fe, K, Mg, Na, and P) in the brain are the ionic basis for the therapeutic effect of acupuncture. A hypothetical model of the mechanism of acupuncture therapy is described.

Acupuncture Therapy↗

The octopus: a model for a comparative analysis of the evolution of learning and memory mechanisms.

Comparative analysis of brain function in invertebrates with sophisticated behaviors, such as the octopus, may advance our understanding of the evolution of the neural processes that mediate complex behaviors. Until the last few years, this approach was infeasible due to the lack of neurophysiological tools for testing the neural circuits mediating learning and memory in the brains of octopus and other cephalopods. Now, for the first time, the adaptation of modern neurophysiological methods to the study of the central nervous system of the octopus allows this avenue of research. The emerging results suggest that a convergent evolutionary process has led to the selection of vertebrate-like neural organization and activity-dependent long-term synaptic plasticity. As octopuses and vertebrates are very remote phylogenetically, this convergence suggests the importance of the shared properties for the mediation of learning and memory.

Action Potentials↗

[Improving effect of rhizoma Gastrodiae on learning and memory of senile rats].

After giving Rhizoma Gastrodiae to aging rats continuously for 3 months, the process of their learning and memory was observed through step-down test and the content of lipid peroxides (LPO) was determined. It has been found out that Rhizoma Gastrodiae can effectively improve the ability of learning and memmory of these rats and reduce the content of LPO. The result may indicate that it is by clearing away the free-radicals that Rhizoma Gastrodiae improves the brain function.

Aging↗