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If the engram of long-term memory is encoded by structural changes of neuronal circuits, they are expected to be present at distant time points after learning, to be specific of circuits activated by learning, and sensitive to behavioral contingencies. In this review we present new concepts that emerged from in vivo imaging studies that tracked the structural bases of the memory trace. A fine balance of spine formation and spine elimination needed for behavioral adaptation to new experience is regulated by glucocorticoids, which are secreted in synchrony with circadian rhythms and in response to stress. Disruption of glucocorticoid oscillations frequently observed in psychiatric disorders like depression and post-traumatic stress produces spine turnover defects and learning disabilities. These new findings provide a new framework for explaining the potent but complex mnemonic effects of glucocorticoids., (© 2015 médecine/sciences – Inserm.)

The steroids dehydroepiandrosterone sulfate (DHEA-S) and pregnenolone sulfate (Preg-S) are naturally synthetized in the brain. They improve short term and long term memory performances in a variety of learning tasks and models of amnesia in rodents. DHEA-S and Preg-S modulate GABAergic and glutamatergic synaptic transmission through direct interactions with GABA-A, NMDA and/or sigma 1 membrane receptors. In addition, these two neurosteroids facilitate the release of acetylcholine and modulate synaptic plasticity phenomena in cerebral structures, such as the hippocampus, known to play a role in learning and memory processes. The possible links between these actions and the promnestic effects of DHEA-S and Preg-S are discussed in the present review.

Most of the current theories assume that there are multiple forms of memory that are supported by separate brain systems and have different characteristics. Animals studies on the various dual-memory theories have been carried out mainly on the basis of hippocampal system function. Specifically, they have focused on aspects of learning and memory that are impaired (vs. spared) by lesions of the hippocampal formation. However, there are several instances in the animal literature showing that hippocampal lesions actually produced enhanced learning and memory function. Moreover, the acquisition of tasks that are facilitated by hippocampal lesions (or dysfunction) is nevertheless associated, in intact subjects, with specific neurobiological alterations in the hippocampus. This problem has been analysed using two different tasks in mice: a bar-press conditioning and a spatial discrimination task. Results showed that, depending on the task considered, the same pharmacological treatment produced either a facilitation or an impairment of acquisition. Moreover, each task induced significant alterations in hippocampal adenylate cyclase activity but in opposite directions. Together with previous findings, these results suggest that the hippocampus is involved in both the so-called "hippocampal-dependent" and "hippocampal-independent" forms of memory. It is postulated that some of the observed training-induced neurobiological alterations might reflect the interaction between two (or more) competing memory systems at the hippocampal level. Thus, in addition to its proposed specific information processing functions (i.e., relational), the hippocampus would play a role in addressing information to the brain memory system that, in a given situation, has the best adaptive value.(ABSTRACT TRUNCATED AT 250 WORDS)

The Morris water-maze has been designed to test spatial orientation ability, learning and memory processes. In order to improve the analyse of the organization of the trajectory of rats, during the training phase, a computer program was elaborated. The study of the effect of a benzodiazepine, diazepam, was chosen to illustrate and validate this methodological approach. Results showed that rats pre-treated with diazepam (2 mg/kg) presented an impairment of spatial learning associated with the occurrence of a stereotyped circular swimming behaviour.

Tianeptine, a molecule with antidepressant properties, was found to affect certain learning and memory impairments induced by chronic alcoholism and aging in the mouse. Impairment in spontaneous alternation induced by chronic (12 months) alcohol intake and accelerated loss of spatial learning skills related to aging disappeared totally after administration of tianeptine (10 mg.kg-1). In certain situations (discrimination acquisitions), tianeptine was uneffective in older animals at this dosage, but had a facilitating effect in young animals. The effects of tianeptine on serotonin mediated transmission and the probable implication of hypofunctioning central cholinergic systems in the observed impairments are discussed. Tianeptine might reduce the inhibiting action of serotonin terminaisons on acetylcholine release and might thus permit normal cholinergic transmission.

Convergent data demonstrate that excitatory amino acid systems (glutamate and aspartate) participate in synaptic plasticity of the central nervous system. Their action is mediated by at least three subclasses of receptors which have been characterized on the basis of their selective affinity to N-methyl-D-aspartate (NMDA), quisqualate and kainate. NMDA receptors appear to be directly involved in the induction of long-term potentiation (LTP) at the hippocampal level, and quisqualate/kainate receptors in the expression of LTP. This suggests that excitatory amino acid systems may have an important role in learning and memory. However, how these systems interfere with memory processes remains largely unknown. We have isolated a pseudopeptide, gamma-L-glutamyl-L-aspartate (gamma-LGLA) (Ungerer et al., 1988), which has the pharmacological properties of a competitive antagonist at NMDA receptors as evidenced by biochemical studies and by the fact that gamma-LGLA selectively blocks the clonico-tonic seizures induced by NMDA, while having no significant action against seizures induced by kainate or quisqualate. Elsewhere, gamma-LGLA is devoid of toxicity at the doses used. Behavioral effects of gamma-LGLA were first studied in a Y-maze avoidance learning task. Animals had to leave the start alley within 5 sec. (temporal component) and to choose the left alley of the maze (spatial component) to avoid footshock. They underwent one trial every minute and were trained to a criterion of 7 correct out of 8 consecutive trials. Retention was tested either 1 h, 3 h, 6h, 24 h, 7 days or 21 days after acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)

Rats were trained in 4 consecutive trials to obtain a liquid reward in a labyrinth system. Drugs were given s.c. 2-4 hours before each trial, and starting time (ST), running time (RT) and number of errors (NE) were recorded on the fourth trial. Hydergine reduced NE independently of its effect on ST and RT. Dihydroergocristine and dihydroergocornine prolonged ST, dihydro-alpha-ergokryptine reduced NE whilst dihydro-beta-ergokryptine did not induce any significant effect on the three parameters. These results demonstrated that none of the Hydergine components exerts a similar effect to that of Hydergine in this model. It is also known that Hydergine influences neurotransmitters like serotonin, dopamine, noradrenaline and acetylcholine in vivo and in vitro. Therefore, the effects of Hydergine on cognitive functions in rats appear to be the consequence of its different actions on the cerebral transmission.

Chronic treatment of monkeys with Cannabis reduce the speed of acquisition of learned behavior, yet, learning is nevertheless possible. After acquisition, Cannabis administration disturb the responses in the learning test. In this two experimental procedures, tolerance occurs to the effects of Cannabis.

In the present work, a study of the number of functional receptors has been made with 3HQNB given to resting awaken animals during a learning process. Ageing leads to a decrease in the ability of learning associated with an increase in the number of large movements. The number of cholinergic receptors is also reducel if we compare 22 month old animals with 4 month old animals maintained under usual conditions. Learning conditioning leads to a stimulation of the cholinergic system with a release of acetylcholine. The mediator takes the 3HQNB out of its fixation areas which causes an apparent decrease in the number of receptors. This result is more significant in young animals than in aged ones because of the possibility of activation in the cholinergic system. The treatment by dihydroergotoxine partially re-establishes the learning abilities in animals and, at the same time, increases the number of cholinergic receptors This effect could explain the actions of this drug on the memory process in ageing persons.

Milacemide (2-n-pentylaminoacetamide . HCl) is an anti-epileptic which improves the mood, vigilance and sociability of treated patients. By metabolic charting with radioactive deoxyglucose it is possible to estimate local consumption of glucose in the various regions of the brain in rats treated with milacemide in comparison with rats treated with a placebo. It would seem that milacemide exerts an appreciable activating effect principally on pathways with sensory functions. The activation of the metabolism of cerebral energy in these regions may explain the behavioural improvements observed in the rat and in the first clinical trials in man.

Immediate posttrial halothane anaesthesia accelerates the extinction of two previously acquired operant tasks--barpress learning or modified K-maze learning. This acceleration is not due to any motor impairment. These results are not consistent with the hypothesis of amnestic effects of halothane anaesthesia; they are interpreted in terms of aversive effects.

The behaviour of rats exposed to various levels of lead acetate (0.5 ; 1 ; 2 and 4% in dam's diet) before weaning was recorded between 2 and 6 months of age. Higher locomotor and exploratory activities as well as better scores in active avoidance conditioning were observed in the 4% lead-treated rats. For lower doses, no behavioural alterations were recorded despite both detarded growth and increased mortality.

The adrenocorticotropic hormone (ACTH) is produced within the cell body of hypothalamic neurons by proteolytic cleavage of its large precursor molecule, pro-opiomelanocortin. These neurons distribute ACTH-containing nerve endings throughout the central nervous system. ACTH is able to evoke motor and behavioural responses and to modify neuronal metabolism. Since ACTH has been shown to regulate glucose uptake and utilization, its implication in the adaptative response to stress situations, such as cerebral hypoxia, deserves further investigations.

Alpha-melanocyte stimulating hormone (alpha-MSH) is a tridecapeptide secreted by intermediate lobe cells and synthesized in the brain as well. As a hormonal peptide, the physiological function of alpha-MSH consists mainly in the control of pigment movements within dermal melanophores. At the pituitary level, alpha-MSH secretion is under multifactorial control: it is inhibited by dopamine and GABA and stimulated by corticoliberin (CRF), thyroliberin (TRH), beta-adrenergic agonists and (or) serotonin. Identification of alpha-MSH containing neurons in the hypothalamus and other brain regions (septum, thalamus, mid-brain, striatum, hippocampus, cerebral cortex and spinal cord) has been carried out by means of immunological and biochemical techniques combined with bioassays. In the central nervous system (CNS) as in the hypophysis, alpha-MSH is synthesized from a high molecular weight precursor, pro-opiomelanocortin (POMC). Maturation of this protein yield similar end products in the hypothalamus and the intermediate lobe. Several peptides chemically related to alpha-MSH are generated including the desacetyl and monoacetyl (authentic alpha-MSH) forms; the latter has the greatest behavioral activity. The demonstration that alpha-MSH has numerous central nervous system effects has raised the possibility that this neuropeptide acts as a neuromodulator or a neurotransmitter. In the rat, intra-cerebroventricular administration of ACTH/MSH peptides induces the stretching-yawning syndrome (SYS) which is frequently preceded by excessive grooming. This excessive grooming is blocked by neuroleptics indicating that the central dopaminergic neurons are implicated in this behavioral effect of the peptide. alpha-MSH is involved in memory, arousal and attention; in hypophysectomized animals, the learning ability is restored after administration of MSH or related peptides. Injection of alpha-MSH delays also extinction of passive avoidance behavior and affects performances motivated by hunger as well as aggressive behavior. Recent studies concerning the role of alpha-MSH have been undertaken in human beings. The effects of MSH-related peptides favour a role of these peptides in arousal: they maintain a high level of vigilance and improve visual discrimination. These behavioral changes were accompanied by marked changes in CNS electrophysiology. Current studies, which aim at establishing a neurotransmitter function for alpha-MSH, concern the distribution and characterization of alpha-MSH receptors in the central nervous system and the mechanism controlling the release of neuronal alpha-MSH.

Eight patients with Alzheimer's disease presenting whith memory difficulties and no significant intellectual deterioration were treated with 9 grams daily. Choline base orally for 3 weeks. Quantitative testing, which evaluate memory capabilities such as learning and recall after delays of 1 hour and 24 hours, were used before and after the administration of Choline. The results of a global statistical analysis did not show any significant difference in the performances obtained before and after choline. However, in two patients, recall performance improvement was confirmed clinically. Most likely, these two patients were suffering from an mild foorm of Alzheimer's disease.