[Synaptic tagging and memory trace]. / La 'marca sinaptica' y la huella de la memoria.

AIM: To present a panorama of the main features and possible identity of the synaptic tag, such as to discuss some of its functional implications. DEVELOPMENT: Long-term potentiation (LTP) constitutes a very attractive synaptic/cellular memory model. LTP, like memory, can manifest itself early (essentially depending on the modification of pre-existing proteins at synapse) and late (depending on new protein synthesis). As LTP is a highly specific phenomenon, a dilemma arises: how can the proteins, required to plastic change stabilization, that are synthesized at the soma of a neuron containing thousands of synaptic contacts--all depending of the same nucleus--go to the appropriate synapses? In this review, we present some of the models that intend to explain this question, making emphasis on synaptic tagging hypothesis. Some of the main findings that have contributed to tagging hypothesis are exposed. The local protein synthesis and the activation of protein kinases are analyzed as candidates to be the synaptic tag. Additionally, some of the functional implications of synaptic tagging are discussed. CONCLUSIONS: The synaptic tagging hypothesis offers a very flexible and reasonable solution to the specificity of long-lasting synaptic changes. Although some of the tagging features are known, the synaptic tag identity has not yet been elucidated. It seems that there is not a unique synaptic tag, but there are rather multiple molecular synaptic tags involved. Each of them might function as a synaptic tag under particular circumstances. Each might be differentially recruited by specific stimuli and mediate plasticity over different time domains.

La ‘marca sináptica’ y la huella de la memoriar / Synaptic tagging and memory trace

Presentar una visión de las principales características y posible identidad de la marca sináptica, así comodiscutir algunas de sus implicaciones funcionales. Desarrollo. La potenciación sináptica a largo plazo, dadas sus características, se ha impuesto como un modelo sinapticocelular de memoria muy atractivo. De modo similar a la memoria, puede manifestarse como temprana (dependiente fundamentalmente de la modificación de proteínas preexistentes en la sinapsis) otardía (dependiente de la síntesis de nuevas proteínas). Debido a que la potenciación sináptica a largo plazo es un fenómeno altamente específico, surge un dilema: ¿cómo llegan a las sinapsis apropiadas las proteínas requeridas para la estabilizacióndel cambio plástico en una neurona que normalmente posee miles de contactos sinápticos, todos dependientes del mismo núcleo? En este trabajo se presentan algunos de los modelos que aportan posibles soluciones a este interrogante, haciendo énfasisen la hipótesis del marcaje sináptico. Se exponen los principales hallazgos que han ido conformando esta hipótesis y se analiza la síntesis local y la activación de proteincinasas como posibles candidatos de ser la marca sináptica. Adicionalmente, sediscuten algunas implicaciones funcionales del marcaje sináptico. Conclusiones. La hipótesis de la marca sináptica ofrece una explicación muy flexible y razonable acerca de la especificidad del cambio sináptico duradero. Aunque se conocen algunas desus características, la identidad de la marca no se ha dilucidado aún. Al parecer, existen múltiples marcas que, al ser reclutadas por estímulos específicos, median los efectos plásticos en diferentes dominios temporales

To present a panorama of the main features and possible identity of the synaptic tag, such as to discuss someof its functional implications. Development. Long-term potentiation (LTP) constitutes a very attractive synaptic/cellular memory model. LTP, like memory, can manifest itself early (essentially depending on the modification of pre-existing proteins atsynapse) and late (depending on new protein synthesis). As LTP is a highly specific phenomenon, a dilemma arises: how can the proteins, required to plastic change stabilization, that are synthesized at the soma of a neuron containing thousands ofsynaptic contacts –all depending of the same nucleus– go to the appropriate synapses? In this review, we present some of the models that intend to explain this question, making emphasis on synaptic tagging hypothesis. Some of the main findings that have contributed to tagging hypothesis are exposed. The local protein synthesis and the activation of protein kinases areanalyzed as candidates to be the synaptic tag. Additionally, some of the functional implications of synaptic tagging are discussed. Conclusions. The synaptic tagging hypothesis offers a very flexible and reasonable solution to the specificity oflong-lasting synaptic changes. Although some of the tagging features are known, the synaptic tag identity has not yet been elucidated. It seems that there is not a unique synaptic tag, but there are rather multiple molecular synaptic tags involved.Each of them might function as a synaptic tag under particular circumstances. Each might be differentially recruited by specific stimuli and mediate plasticity over different time domains

[Comparative study of bilateral lesions in the entorhinal cortex and in the fimbria fornix]. / Estudio comparativo de la lesión bilateral de corteza entorrinal y de la fimbria-fórnix.

INTRODUCTION: Numerous reports show that lesions to hippocampus afferents, such as the entorhinal cortex (EC) and the fimbria fornix (FF), exert an effect on memory in rodents. There are, however, no long term comparative studies that show which of these lesions could be most useful as a model for studies into neuroplasticity. MATERIAL AND METHODS: Young male Sprague Dawley rats were used. Bilateral electrolytic lesion was caused to the EC or the FF was damaged by transection. One, four or 12 weeks later the animals were evaluated in a Morris water maze, first with an invisible platform and then with the platform within view. The results from the two groups were compared to each other and to those obtained from healthy controls and subjects with false lesions by means of a variance analysis. RESULTS: In the test with an invisible platform, both types of lesion gave rise to serious, irreparable involvement of the spatial memory of the animals, at least up to 12 weeks after the lesion. The test with the visible platform revealed significant differences between animals with lesion to the EC evaluated at 12 weeks, which suggests the development of some visual or motor deterioration in these animals. CONCLUSIONS: Although both lesions gave rise to behavioural deterioration that was irreversible in the long term in rodents, the lesion to the FF seems to be a better model for evaluating specific effects on learning and memory, since the lesion to the EC apparently triggers additional sensory and motor involvement.

[Glutathione in cognitive function and neurodegeneration]. / El glutatión en la función cognitiva y la neurodegeneración.

OBJECTIVE: To review the main findings on the glutathione role in cognitive function and synaptic plasticity processes, as well as, its involvement in neurotrophic and neurodegenerative events in rodents. DEVELOPMENT: The tripeptide glutathione and its related enzymes participate in the maintenance of oxidant homeostasis in aerobic cells. Oxidative damage to neuronal components underlies the molecular basis of neurodegeneration and brain aging. Several biomolecules with redox dependent activity are involved in the neuronal plasticity events that have a role in learning and memory functions. The maintenance of normal glutathione level is important for acquisition, but not consolidation, of spatial memory. Glutathione unavailability induces failures in hippocampal synaptic plasticity mechanisms, which are possibly related to a spatial memory deficit. On the other hand, several studies have suggested that the beneficial effects of neurotrophic treatments are mediated by the modulation of antioxidant defense mechanisms. In fact, nerve growth factor treatment to cognitively impaired rats stimulates glutathione reductase and can prevent the increases in glutathione peroxidase activity, pointing these enzymes as possible intracellular targets of neurotrophin actions on oxidant homeostasis. CONCLUSION: There is a closed link between glutathione metabolism and oxidant homeostasis, which is expressed in learning and synaptic plasticity deficits in conditions of low glutathione content, as well as, in neurodegeneration induced glutathione metabolism changes that can be prevented by neurotrophic treatment

[Interactions between the hippocampus and the amygdala in synaptic plasticity processes. A key to understanding the relations between motivation and memory]. / Interacciones entre el hipocampo y la amígdala en proceso de plasticidad sináptica. Una clave para entender las relaciones entre motivación y memoria.

INTRODUCTION: Memory is initially stored as a transitory change that can become consolidated and converted into a long term memory trace. Consolidation largely depends on the emotional state. It is known that the hippocampus plays a role in the consolidation process of certain types of memory and that the amygdala might modulate the consolidation of the memory traces in other parts of the brain. The interaction between these two structures is crucial in many forms of learning and memory. METHOD: The hippocampus, as well as the amygdala, display a type of synaptic plasticity known as long term potentiation (LTP), which is considered to be a cellular memory mechanism. Recently, it has been reported that the consolidation of the hippocampal LTP may be modulated, like memory, by the emotional state and by the activation of the basolateral amygdala. These findings, taken as a whole, can help to explain how the processes of consolidation of memory take place. At the same time they also constitute a more physiological model of the learning and memory processes, which will provide us with a more accurate understanding of the mechanisms behind the consolidation of the memory.

[Cellular mechanisms of neuroplasticity]. / Mecanismos celulares de la neuroplasticidad.

OBJECTIVE: To present a unified vision of the principal known mechanisms of neuroplasticity, emphasizing their universality. DEVELOPMENT: The concept of the central nervous system as an immutable entity has been considerably modified during the second half of the 20th century. Neuroplasticity, that is the ability of the brain regarding change and repair is expressed in different ways, from functional modifications of existing structures to the formation, by growth and proliferation, of new structures and neurons. This study considers the molecular and cellular mechanisms of neuroplastic phenomena and classifies them into two main groups: plasticity due to growth, including the mechanisms of axonal regeneration, collateralization and reactive synaptogenesis; and functional plasticity, which includes changes in the efficacy of synaptic transmission such as long-term potentiation and the activation of silent synapses. We also describe some of the relations of neuroplastic phenomena with disease of the central nervous system, together with examples of physiological, physical and pharmacological factors which may be used in future as therapeutic tools to stimulate and modulate neuroplasticity. CONCLUSION: Neuroplastic mechanisms show a high degree of phylogenetic and ontogenetic conservation. They are important both in the genesis of disorders and disease of the nervous system and for its repair after different types of damage and trauma. Modulation of neuroplastic mechanisms by physical and chemical agents would appear to be one of the most powerful therapeutic tools of restorative neurology.

[A comparative study of lesion of the fimbria-fornix by aspiration and by transsection]. / Estudio comparativo de la lesión de fimbria-fórnix por aspiración y transección.

INTRODUCTION: Lesion of the fimbria-fornix causes dysfunction of learning processes and has been used in animal models for the study of Alzheimer's disease. MATERIAL AND METHODS: With the objective of comparing the efficacy of two methods of producing a lesion of the fimbria-fornix, 40 young male Sprague-Dawley rats were distributed in four experimental groups: control (6), falsely lesioned (8), lesion due to aspiration (12) and lesion due to transection (14). RESULTS: The results showed that whilst with both techniques, in rats, serious cognitive defects were produced, as expressed by the high latencies of escape and small number of crossings of Morris's aquatic labyrinth, the aspiration lesion led to greater mortality than the transection lesion did. Similarly, the aspiration technique in rats induced hyperactivity, aggressiveness and tigmotaxia, while in the rats with lesions due to transection tigmotaxia ceased after their first attempts and hyperactivity on the second day of training. CONCLUSION: These results would suggest that a bilateral lesion due to transection of the fimbria-fornix is an effective alternative to an aspiration lesion to interrupt this pathway.