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The biochemistry of learning and memory.

An overview of some of the biochemical and molecular events involved in the process of learning and memory are presented in a short review. Two invertebrate models of learning are considered: the gill-withdrawal reflex of Aplysia and avoidance learning in Drosophila melanogaster. Particular attention is paid to the biochemical mechanisms underlying both the development of long-term potentiation (LTP) and passive avoidance learning (PAL) in the young chick. The role of several biological molecules in learning and memory are considered, for example, protein kinase C (PKC), Ca(++)-Calmodulin kinase II (CaMKII), GAP-43, and glutamate receptors.

Adenylyl Cyclases↗

Contributions of cingulate cortex to two forms of spatial learning and memory.

The contribution of anterior and posterior cingulate cortical areas to spatial learning and memory was examined in 4 experiments using the place-navigation task. Rats with complete bilateral cingulate cortex aspiration or aspiration of posterior cingulate cortex (area 29) alone could not swim directly to a hidden platform located in a fixed place. When animals with these lesions were tested for 40 d in a place-alternation task in which they received 16 daily trials with the platform placed in a new location each day, they did not show reliable improvement in place navigation. The inability to swim to changing locations or to a single location was not overcome by preoperative training in these tasks. Rats with anterior cingulate cortex aspirations showed a less severe impairment in both tasks and, with more training than is necessary for control rats, they acquired near-normal place-navigation accuracy. Rats with complete cingulate cortex aspiration were almost as accurate as control rats in learning to swim to a visible platform. The results imply that posterior cingulate areas play an essential role in the use of topographical information, probably by transmitting and elaborating information passing between the hippocampal system and neocortical association areas.

Animals↗

Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studies.

Nicotine alleviates cognitive impairment associated with a variety of health conditions. We examined the effect of chronic nicotine treatment on adult-onset hypothyroidism-induced impairment of learning and memory in rats. Hypothyroidism was induced by surgical removal of thyroid glands (thyroidectomy). One month later, chronic nicotine treatment (1 mg/kg sc, twice/day) was instituted for 4-6 weeks. Test of hippocampus-dependent spatial learning and memory in the radial arm water maze showed that hypothyroidism impaired learning as well as short-term and long-term memory retention. Chronic nicotine treatment reversed the hypothyroidism-induced learning and memory impairment. In normal rats, chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anesthetized hypothyroid rats showed severe reduction of both early-phase and late-phase long-term potentiation (LTP) magnitude, which was reversed in nicotine-treated hypothyroid rats. These results show that chronic nicotine treatment prevents hypothyroidism-induced impairment of spatial cognition and LTP.

Action Potentials↗

Selecting a model system for neurobiological studies of learning and memory.

This article discusses the logic underlying the use of invertebrate model systems for investigating the neurobiological basis of learning and memory, the kinds of questions which can be asked of these systems as well as their limitations. A model system selected to answer specific questions about learning and memory is most useful if its selection is based on strategy rather than chance.

Animals↗

Effects of insulin-dependent diabetes on learning and memory efficiency in adults.

Previous work with elderly adults with maturity-onset non-insulin-dependent diabetes has demonstrated the presence of significant learning and memory deficits which are correlated with the degree of chronic hyperglycemia. This study was conducted to examine learning and memory processes in a group of 82 younger adults (mean age = 33.4 years) with a long history (mean duration = 26.2 years) of childhood-onset insulin-dependent diabetes. Contrary to expectation, diabetic subjects performed as well as a group of 82 age- and SES-matched nondiabetic control subjects on all measures of learning and memory. On the other hand, they performed significantly worse on measures of psychomotor efficiency, with degree of chronic hyperglycemia being the best predictor of psychomotor slowing. These findings, together with earlier studies of elderly diabetic patients, suggest that specific neural systems within the aging brain may be differentially sensitive to the "toxic" effects of chronic hyperglycemia.

Adult↗

[Effects of calcium on ability of learning and memory in rats exposed to low level lead before and after birth].

OBJECTIVE: To investigate the effects of calcium on learning and memory ability of rats exposed to low level lead before and after birth. METHODS: Wistar dam rats were randomly divided into normal group, lead-contaminated group and lead with Ca group. Corresponding food and water were given to pregnant rats from d 15 of gestation and to young rats till 7 w after birth. The weight of brain and hippocampus, blood lead content, serum calcium content, learning and memory ability of young rats were tested. RESULT: The blood lead concentrations: lead-contaminated group was the highest, lead with Ca group the second and normal group the lowest. Serum calcium concentrations: normal group and lead with Ca group were both higher than lead contaminated group. Ability of learning and memory: lead with Ca group was better than lead-contaminated group, but poorer than normal group. No differences were found upon the weight of brain and hippocampus in all groups. CONCLUSION: A minilaparotomy approach for curative resection of rectal cancer may be an ideal alternative approach to conventional laparotomy.

Animals↗

The olfactory tubing maze: a new apparatus for studying learning and memory processes in mice.

In order to have an ethologically relevant behavioral task, we developed the olfactory tubing maze to study learning and memory processes in mice. Mice have to make two olfactory-reward associations across three training sessions. The maze is made up of four identical testing chambers connected to each other by semicircular cylinders. After having chosen one of two odors presented on each side of a testing chamber, the mice have to run to the next testing chamber. From one testing chamber to the next, the side for presentating each odor is randomly assigned. The mouse must run through the entire circular maze to make a response at the four testing chambers. A complete session consists of 20 trials made by running five times clockwise through the maze with 4 trials per run. The training and data recording are fully automated by a custom-made software program. Three different experiments were performed. The results indicated that mice can easily make the olfactory discriminative associations in this new apparatus. Analysis of the data suggests that it would be possible using this olfactory tubing maze to study sub-categories of memory similar in some respects to those observed in humans. Consequently, possible effects on learning and memory of classical treatments (i.e. pharmacological or lesions) or genetic modifications in transgenic or gene-targeting mice could be tested.

Animals↗

Long-term potentiation in the amygdala: a mechanism for emotional learning and memory.

In the mammalian brain, LTP is an enduring form of synaptic plasticity that is posited to have a role in learning and memory. Compelling new evidence for this view derives from studies of LTP in the amygdala, a brain structure that is essential for simple forms of emotional learning and memory, such as Pavlovian fear conditioning in rats. More specifically, antagonists of the NMDA receptor block both amygdaloid LTP induction and fear conditioning, fear conditioning induces increases in amygdaloid synaptic transmission that resemble LTP, and genetic modifications that disrupt amygdaloid LTP eliminate fear conditioning. Collectively, these results provide the most-convincing evidence to date that LTP mediates learning and memory in mammals.

Amygdala↗

Complementary molecular models of learning and memory.

The functional capabilities of the brain are formally characterizable interms of a finite system along with a memory space which it can manipulate. Two types of learning are possible: (1) modification-based learning, associated with alternate realizations of the finite system; (2) memory-based learning, associated with the assimilation, manipulation, and retrieval of memories. Constructive models which fulfill these conditions and which at the same time operate on the basis of molecular information processing principles have certain general features. We describe these features in terms of two interfaced submodels, the first for the finite system and the second for the memory space. The finite system may be realized by networks of neurons in which the specificity of enzyme molecules controls the nerve impulse. Such a realization is amenable to modification-based learning mediated by processes analogous to those of natural evolution and selective theories of antibody synthesis. The memory space is realizable by networks of neurons in which the conformation of dendritic receptor molecules controls the nerve impulse. In this case certain neurons firing in response to an external input undergo sensitization at the dendrites and in such a way that they are loadable and later callable by reference neurons, thereby allowing for reconstruction of manipulation of the firing pattern associated with this input. The overall construction makes a large number of biochemical, anatomical, physiological, and psychological predictions which are either testable or in good agreement with fact.

Brain↗

Effects of timosaponins on learning and memory abilities of rats with dementia induced by lateral cerebral ventricular injection of amyloid beta- peptide.

OBJECTIVE: To investigate the effects of timosaponins, one group of the two major components of Anemarrhean asphodeloides Bge, on the learning and memory capacities of rats with dementia induced by amyloid beta-peptide (25-35) [Abeta (25-35)]. METHODS: Sixty SD rats were randomized into 6 groups (n=10) and except for those in the control group, all other rats were subjected to lateral cerebral ventriclar injection of aggregated Abeta (25-35) to prepare rat models of dementia. Twenty- four hours after the injection, the rats received intragastric administration of timosaponins at 3 different doses (treatment group) or Ginkgo biloba extract EGB761 on a daily basis for 14 consecutive days. From postoperative days 8 to 14 after Abeta (25-35) injection, Morris water maze test was performed to evaluate the effects of Abeta (25-35) and the therapeutic agents timosaponins on the learning and memory capacity of the rats. On day 14, the level of malonaldehyde (MDA), superoxide dismutase (SOD) activity and total antioxidation capacity in the brain tissue of the rats were measured. RESULTS: Abeta (25-35) induced significant learning and memory impairment in the rats, which had lowered SOD activity and total antioxidation capacity (P<0.01) with elevated MDA level (P<0.05). Compared with the rats in dementia model group, those receiving timosaponin treatment at different doses all manifested alleviation of learning and memory impairment (P<0.05), with enhanced SOD activity (P<0.05) and total antioxidation capacity (P<0.01) and reduced MDA level (P<0.05) in the brain tissue. CONCLUSION: Timosaponins can remarkably enhance the learning and memory capacities in rats with Abeta (25-35)-induced dementia, presumably in relation to their actions to promote the scavenging of the free radicals.

Alzheimer Disease↗

[Distribution of substance P and its receptor in the marginal division of rat striatum and its association with the function of learning and memory].

OBJECTIVE: To investigate the distribution of the substance P (SP) and its receptor in the marginal division (MrD) of rat striatum and to understand the relationship between SP and the learning and memory function of rats. METHODS: Using immunohistochemistry and in situ hybridization techniques, the distribution of SP and its receptor in the MrD was studied, and the relationship between the SP and learning and memory of the MrD was observed by means of SP receptor gene knockout in combination with Y-maze test. RESULTS: Numerous SP immunopositive fibers and large quantities of SP receptor protein and NK1 mRNA were identified in the MrD of rat striatum. After knockout of the SP receptor gene in the MrD, the ability of learning and memory of the rats was obviously decreased. CONCLUSION: SP and its receptor in the MrD may play important roles in the learning and memory function of rat, possibly through the regulation of the neurotransmitters as 5-HT by SP via NK1 receptor.

Analysis of Variance↗

[Participation of the genetic apparatus in memory and learning phenomena].

The first series of experiments showed that inhibition of the proteins synthesis followed by memory disorders, was reflected in decrease of the synaptosomal proteins fraction which was identified as the cholinoreceptor protein. Another series of experiments: training of rats to use unpreferred paw, showed the system acetylcholine-acetylcholinesterase to be directly connected with memory phenomena, and the synthesis of this enzyme to be induced by genetic apparatus. The third series of experiments showed that feeding of rats with small doses of aminoacids for a long time leads to regular shifts in distribution of both the aminoacids and the monoamines. The aminoacids increasing the brain activity were found to activate the production of cycle-adenyl acid. Those aminoacids which inhibit the brain activity, decrease the production of cyclic-AMP. Tranquilizers which decrease the level of monoamines and inhibit the brain activity, also decrease the production of cyclic-AMP. Antidepressants inhibiting MAO and increasing the level of monoamines in the brain, activate the production of cyclic-AMP. As the monoamines act via cyclic-AMP and the latter participates in suppression of DNA, the mechanism of involvement of the genetic apparatus in regulation of memory phenomena and learning, becomes more apparent.

Acetylcholine↗

Molecular mechanisms underlying emotional learning and memory in the lateral amygdala.

Fear conditioning is a valuable behavioral paradigm for studying the neural basis of emotional learning and memory. The lateral nucleus of the amygdala (LA) is a crucial site of neural changes that occur during fear conditioning. Pharmacological manipulations of the LA, strategically timed with respect to training and testing, have shed light on the molecular events that mediate the acquisition of fear associations and the formation and maintenance of long-term memories of those associations. Similar mechanisms have been found to underlie long-term potentiation (LTP) in LA, an artificial means of inducing synaptic plasticity and a physiological model of learning and memory. Thus, LTP-like changes in synaptic plasticity may underlie fear conditioning. Given that the neural circuit underlying fear conditioning has been implicated in emotional disorders in humans, the molecular mechanisms of fear conditioning are potential targets for psychotherapeutic drug development.

Amygdala↗

Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory.

The effect of alcohol-aqueous extract (1:1) from Rhodiola rosea L. roots on the processes of learning and memory is studied on rats. Several methods of active avoidance with negative and positive reinforcements are used, as well as of passive avoidance. Using the maze-method with negative (punitive) reinforcement, it has been found that Rhodiola extract in a single dose of 0.10 ml per rat essentially improves learning and retention after 24 hours. Significant improvement of the long-term memory is also established in memory tests after 10-day treatment with the same dose of the extract. In the other two doses tested (0.02 and 1.0 ml per rat) the extract has no substantial effect on learning and memory. In a dose of 0.10 ml per rat the Rhodiola extract had a favourable effect on the training process using the "staircase" method with positive (food) reinforcement as well. With the other methods used (active avoidance method with negative reinforcement "shuttle-box" and passive avoidance methods "step down" and "step through") Rhodiola extract in the dose used (0.10 ml per rat) had no substantial effect on learning and memory (a certain deterioration of the training process was even observed using the "shuttle-box" method, while the "step-down" method resulted in deterioration of the memory). The great significance of the method used for studying the effects of the pharmacological agents on learning and memory for the results obtained is evident.

Administration, Oral↗

Attentional functions of cortical cholinergic inputs: what does it mean for learning and memory?

The hypothesis that cortical cholinergic inputs mediate attentional functions and capacities has been extensively substantiated by experiments assessing the attentional effects of specific cholinotoxic lesions of cortical cholinergic inputs, attentional performance-associated cortical acetylcholine release, and the effects of pharmacological manipulations of the excitability of basal forebrain corticopetal cholinergic projections on attentional performance. At the same time, numerous animal experiments have suggested that the integrity of cortical cholinergic inputs is not necessary for learning and memory, and a dissociation between the role of the cortical cholinergic input system in attentional functions and in learning and memory has been proposed. We speculate that this dissociation is due, at least in part, to the use of standard animal behavioral tests for the assessment of learning and memory which do not sufficiently tax defined attentional functions. Attentional processes and the allocation of attentional capacities would be expected to influence the efficacy of the acquisition and recall of declarative information and therefore, persistent abnormalities in the regulation of the cortical cholinergic input system may yield escalating impairments in learning and memory. Furthermore, the cognitive effects of loss of cortical cholinergic inputs are augmented by the disruption of the top-down regulation of attentional functions that normally acts to optimize information processing in posterior cortical areas. Because cortical cholinergic inputs play an integral role in the mediation of attentional processing, the activity of cortical cholinergic inputs is hypothesized to also determine the efficacy of learning and memory.

Attention↗