RESUMO
Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy considered to be the cellular basis of memory. LTP consists of an early, protein synthesis-independent phase (E-LTP) and a late phase that depends on protein synthesis (L-LTP). Application of a weak tetanus can induce E-LTP in the dentate gyrus (DG) which can be reinforced into L-LTP by direct stimulation of the basolateral amygdala (BLA) within 30 min before or after LTP induction (structural LTP-reinforcement). LTP can be depotentiated by low-frequency stimulation (LFS) to the same synaptic input if applied shortly after tetanization (<10 min). Here, we addressed the question of whether stimulation of the BLA is able to recover LTP at depotentiated synaptic inputs. We hypothesized that E-LTP can activate synaptic tags, which were then reset by depotentiation. Stimulation of the BLA thereafter could beneficially act on tag-reactivation as well as on the activation of the synthesis of plasticity-related proteins (PRPs), normally captured by the tags and thus transforming E-LTP into L-LTP. Our results show, that BLA-stimulation was not able to reactivate the resetting of tags by depotentiation in the DG of freely moving rats.
Assuntos
Tonsila do Cerebelo/fisiologia , Giro Denteado/fisiologia , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Sinapses/fisiologia , Animais , Estimulação Elétrica , Masculino , Ratos , Ratos Wistar , Período Refratário Eletrofisiológico/fisiologiaRESUMO
Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy considered to be the cellular basis of memory. LTP consists of an early, protein synthesis-independent phase (E-LTP) and a late phase that depends on protein synthesis (L-LTP). In water-deprived rats E-LTP in the dentate gyrus (DG) can be reinforced into L-LTP, if the rats were allowed to drink within 15 min after E-LTP induction (behavioral LTP-reinforcement, BR). LTP can be depotentiated by low-frequency stimulation (LFS) to the same synaptic input if applied shortly after tetanization (<10 min). Here, we addressed the question of whether a BR protocol is able to recover LTP at depotentiated synaptic inputs. We show that LTP, depotentiation, LFS and BR specifically interact within one afferent input, which could be explained by the "synaptic tagging" hypothesis outlined by [Frey and Morris (1997) Nature 385:533-536]. E-LTP induced by a weak tetanus (WTET) sets tags in the activated inputs which are able to capture and to process plasticity-related proteins (PRPs) required for L-LTP, the synthesis of which was induced by BR. Synaptic tags could be reset by LFS. BR alone was unable to rescue depotentiated LTP, but the combination of BR and subsequent WTET transformed E-LTP into L-LTP. We show that LTP, LTD and behavioral stimuli alternatively and reversibly affect a single afferent input for long periods of time by LTP as well as LTD mechanisms, competing with each other under the influence of different concurrent stimuli. Affective modulation can shift the balance to one or the other. We show that the result will depend not only on the last stimulus, but on the history of previous stimuli applied to the specific input. Afferent stimuli activate alternative, but partially overlapping cascades with long-lasting consequences for the input including spaced-associative processes of "synaptic tagging" as well as "cross-tagging" which could be demonstrated in single synaptic afferents to one neuronal population in freely behaving animals.
Assuntos
Comportamento Animal/fisiologia , Giro Denteado/fisiologia , Estimulação Elétrica/métodos , Potenciação de Longa Duração/fisiologia , Motivação , Sinapses/fisiologia , Análise de Variância , Animais , Eletrodos Implantados , Masculino , Modelos Neurológicos , Neurônios Aferentes/fisiologia , Via Perfurante/fisiologia , Biossíntese de Proteínas , Ratos , Ratos Wistar , Fatores de Tempo , Privação de Água/fisiologiaRESUMO
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.
Assuntos
Potenciação de Longa Duração/fisiologia , Memória/fisiologia , Sinapses/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Neurológicos , Plasticidade Neuronal/fisiologia , Sinapses/ultraestruturaRESUMO
Objetivo. 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, se discuten algunas implicaciones funcionales del marcaje sináptico. Conclusiones. La hipótesis de la marca sináptica ofrece unaexplicación muy flexible y razonable acerca de la especificidad del cambio sináptico duradero. Aunque se conocen algunas de sus características, la identidad de la marca no se ha dilucidado aún. Al parecer, existen múltiples marcas que, al ser reclutadaspor estímulos específicos, median los efectos plásticos en diferentes dominios temporales(AU)
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(AU)
Assuntos
Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Memória/fisiologia , Sinapses/fisiologia , Sinapses/ultraestrutura , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismoRESUMO
Long-term potentiation is a form of neural functional plasticity which has been related with memory formation and recovery of function after brain injury. Previous studies have shown that a transient early-long-term potentiation can be prolonged by direct stimulation of distinct brain areas, or behavioral stimuli with a high motivational content. The basolateral amygdala and other subcortical structures, like the medial septum and the locus coeruleus, are involved in mediating the reinforcing effect. We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. It remains to be investigated, however, if such subcortical afferents may also be important for behavioral reinforcement of long-term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. One week after surgery the freely moving animals were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h) control animals, i.e. in non-lesioned and sham-operated rats, early-long-term potentiation could be behaviorally reinforced by drinking 15 min after tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected. This result indicates that the effect of behavioral-motivational stimuli to reinforce long-term potentiation is mediated by subcortical, heterosynaptic afferents.
Assuntos
Vias Aferentes/lesões , Comportamento Animal/fisiologia , Giro Denteado/fisiologia , Potenciação de Longa Duração/fisiologia , Reforço Psicológico , Vias Aferentes/cirurgia , Tonsila do Cerebelo/fisiologia , Animais , Denervação , Ingestão de Líquidos/fisiologia , Estimulação Elétrica , Eletrodos Implantados , Fórnice/lesões , Fórnice/cirurgia , Masculino , Movimento/fisiologia , Via Perfurante/fisiologia , Ratos , Ratos Sprague-Dawley , Recompensa , Privação de Água/fisiologiaRESUMO
Long-term potentiation (LTP) is considered a cellular correlate of memory processing. A short-lasting early-LTP can be prolonged into a late-L TP (>4h) by stimulation of the basolateral amygdala (BLA) or motivational behavioral stimuli in young, but not in aged, cognitively impaired rats. We measured the changes in transmitter release-induced by BLA or behavioral reinforcement-in young and aged cognitively impaired rats, after implanting a microdialysis cannula at the dentate gyrus. Samples were taken under baseline conditions and during stimulation of BLA. Rats were water deprived and tested again next day, taking samples after allowing access to water. Higher concentrations of choline, HIAA, aspartate, glutamate, and glycine were found in baseline samples from young animals compared to aged. In young animals, BLA stimulation increased the levels of ACh and reduced norepinephrine and serotonine, while behavioral reinforcement reduced the levels of glutamate and glycine. These effects were absent among aged rats, suggesting that this reduced neurochemical response might be linked to the impaired LTP-reinforcement reported previously.
Assuntos
Envelhecimento/fisiologia , Giro Denteado/metabolismo , Potenciação de Longa Duração/fisiologia , Neurotransmissores/metabolismo , Acetilcolina/metabolismo , Animais , Ácido Aspártico/metabolismo , Colina/metabolismo , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Ácido Hidroxi-Indolacético/análise , Microdiálise , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
A transient, protein synthesis-independent long-term potentiation (early-LTP, <4 h) can be reinforced into a maintained protein synthesis-dependent late-LTP (>4 h) by specific electrical stimulation of limbic structures (J. Neurosci. 21 (2001) 3697). Similarly, LTP-modulation can be obtained by behavioral stimuli with strong motivational content. However, the requirement of protein synthesis during behavioral reinforcement has not been shown so far. Thus, we have studied here this specific question using a behavioral reinforcement protocol, i.e. allowing water-deprived animals to drink 15 min after induction of early-LTP. This procedure transformed early-LTP into late-LTP. Anisomycin, a reversible protein synthesis inhibitor, abolished behavioral LTP-reinforcement. These results demonstrate that behavioral reinforcement depends on protein synthesis.
Assuntos
Comportamento Animal , Giro Denteado/fisiologia , Potenciação de Longa Duração , Biossíntese de Proteínas , Potenciais de Ação , Animais , Anisomicina/farmacologia , Estimulação Elétrica , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Ratos Wistar , Reforço Psicológico , Privação de ÁguaRESUMO
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.
Assuntos
Encefalopatias/patologia , Córtex Entorrinal/patologia , Fórnice/patologia , Memória/fisiologia , Animais , Encefalopatias/fisiopatologia , Humanos , Masculino , Aprendizagem em Labirinto , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
Long-term potentiation (LTP) in the dentate gyrus can be modulated and prolonged by emotional/motivational influences when concurrently activated. A similar effect on LTP can be obtained by stimulating the amygdala, suggesting that this limbic structure might be part of the neural system involved in behavioural reinforcement. To confirm this we have performed a series of experiments in which the basolateral amygdala was either temporary inactivated by injection of lidocaine or permanently lesioned electrolytically. Both manipulations completely blocked the reinforcing effect of a motivational stimulus (drinking after 24-h deprivation) on LTP at the perforant pathway-dentate gyrus synapses, whilst leaving intact the non-reinforced potentiation. These results demonstrate that the basolateral amygdala is a key structure within the system involved in the modulatory interaction between the affective status of the animal and the mechanisms of functional plasticity.
Assuntos
Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Potenciação de Longa Duração/fisiologia , Reforço Psicológico , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/lesões , Análise de Variância , Anestésicos Locais/farmacologia , Animais , Comportamento Animal/fisiologia , Ingestão de Líquidos , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Lidocaína/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Privação de ÁguaRESUMO
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
Assuntos
Transtornos Cognitivos/etiologia , Glutationa/metabolismo , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/metabolismo , Envelhecimento/fisiologia , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Deficiências da Aprendizagem/etiologia , Transtornos da Memória/etiologia , Fatores de Crescimento Neural/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Oxirredução , Estresse Oxidativo/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
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.
Assuntos
Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Motivação , Transmissão Sináptica/fisiologia , Animais , Humanos , Reforço PsicológicoRESUMO
Glutathione serves the function of providing reducing equivalents for the maintenance of oxidant homeostasis, and besides it plays roles in intra- and intercellular signaling in the brain. Our purpose was to test the effects of depleting tissue glutathione by diethylmaleate (5.3 mmol/kg, intraperitoneal) on brain antioxidant metabolism, nerve growth factor levels, and cognitive performance in rats. Six hours after the treatment, glutathione level in the hippocampus dropped down to 30% of the mean value of vehicle-treated animals and glutathione peroxidase activity also declined. Twenty-four hours after the injection the values had been partially restored. Moreover, the hippocampal and cortical levels of nerve growth factor protein did not change in response to diethylmaleate treatment. Glutathione depletion did not influence the performance of animals in the step-through passive avoidance test, but impairs acquisition in the Morris water maze when given before training. However, when diethylmaleate was administered after acquisition in the same paradigm, it did not affect the retention tested at the following day. Our results suggest that glutathione status is important during acquisition, but not for retention, of spatial memory in maze tasks and they support the hypothesis of the oxidant/antioxidant equilibrium as a key piece acting in the regulation of brain function.
Assuntos
Comportamento Animal/fisiologia , Encéfalo/metabolismo , Glutationa/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Glutationa/antagonistas & inibidores , Glutationa/deficiência , Glutationa Peroxidase/antagonistas & inibidores , Habituação Psicofisiológica/efeitos dos fármacos , Habituação Psicofisiológica/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Maleatos/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Retenção Psicológica/efeitos dos fármacos , Percepção Espacial/efeitos dos fármacos , Percepção Espacial/fisiologia , NataçãoRESUMO
Long-term potentiation (LTP) is a sustained increase in the efficacy of synaptic transmission, based on functional changes involving pre- and postsynaptic mechanisms, and has been considered a cellular model for learning and memory. The sulphurated tripeptide glutathione acts as a powerful antioxidant agent within the nervous system. Recent in vitro studies suggest that the cellular redox status might influence the mechanisms involved in synaptic plasticity. It is not known, however, how glutathione depletion might affect LTP. In the present study, we evaluated the input-output relationships, LTP, and paired-pulse interactions in rats with low glutathione levels induced by systemic injection of diethylmaleate. Our results in anesthetized rats show that the basic synaptic transmission between the perforant pathway and the dentate gyrus granule cells was not affected by glutathione depletion. However, in the same synapses it was not possible to induce prolonged changes in synaptic efficacy (LTP). Paired-pulse facilitation was also absent in the treated animals, suggesting an impairment of short-term synaptic interactions. These findings indicate that low content of glutathione can impair short-term and long-term mechanisms of synaptic plasticity and stress the importance of the redox balance in the normal function of brain circuitry.
Assuntos
Glutationa/metabolismo , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Animais , Estimulação Elétrica/métodos , Glutationa/antagonistas & inibidores , Injeções , Potenciação de Longa Duração/fisiologia , Maleatos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Long-term potentiation (LTP) is a sustained increase in the efficacy of synaptic transmission, based on functional changes involving pre- and postsynaptic mechanisms, and has been considered a cellular model for learning and memory. The sulphurated tripeptide glutathione acts as a poweful antioxidant agent within the nervous system. Recent in vitro studies suggest that the cellular redox status might influence the mechanisms involved in synaptic plasticity. It is not known, however, how glutathione depletion might affect LTP. In the present study, we evaluated the imput-output relationships, LTP, and paired-pulse interactions in rats with low glutathione levels induced by sistemic injection of diethylmaleate. Our results in anesthetized rats show that the basic synaptic transmission between the perforant pathway and the dentate gyrus granule cells was not affected by glutathione depletion. However, in the same synapses it was not possible to induce prolonged changes in synaptic efficacy (LTP). Paired-pulse facilitation was also absent in the treated animals, suggesting an impairment of short-term synaptic intections. These findings indicate that low content of gluthatione can impair short-term and long-term mechanisms of synaptic plasticity and stress the importance of the redox balance in the normal funcion of brain circuitry(AU)
Assuntos
Plasticidade Neuronal , Glutationa , RatosRESUMO
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.
Assuntos
Plasticidade Neuronal/fisiologia , Neurônios/citologia , Animais , Humanos , Neurônios/fisiologiaRESUMO
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.
Assuntos
Fórnice/patologia , Fórnice/cirurgia , Doença de Alzheimer , Animais , Biópsia por Agulha/métodos , Transtornos Cognitivos/diagnóstico , Modelos Animais de Doenças , Aprendizagem/fisiologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Introducción. La lesión de la fimbria-fornix causa disfunciones que afectan los procesos de aprendizaje y ha sido utilizada como modelo animal de enfermedad de Alzheimer. Material y métodos. Con el propósito de comparar la eficacia de dos métodos para producir la lesión de fimbria-fornix, se utilizaron 40 ratas machos jóvenes de la variedad Sprague-Dawley, distribuidas en cuatro grupos experimentales: controles (6), falsas lesionadas (8), lesionadas por aspiración (12), lesionadas por transección (14). Resultados. Los resultados mostraron que si bien ambas técnicas de lesión provocan en las ratas defectos cognitivos graves, según se expresa en las altas la
Assuntos
Modelos Animais de Doenças , Demência , Hipocampo , Memória , Fibras ColinérgicasRESUMO
Se utilizaron 21 ratas Sprague Dawley machos de 8 semanas fueron empleadas para estudiar la influencia de la frecuencia de estimulación sobre la plasticidad sináptica en el giro dentado. Bajo anestesia (hidrato de cloral, 420 mg/kg) se implantaron electrodos de registro en el giro dentado y de estimulación en la vía perforante. Antes de la estimulación tetánica se construyó una curva estímulo-respuesta, las interacciones sinápticas a corto plazo (pulsos pareados con 30, 50, 70 y 90 mseg de intervalo entre estímulos). La estimulación tetánica se hizo utilizando trenes de 10 impulsos cada 10 minutos a frecuencias de 10, 50, 100, 200 y 400 Hz respectivamente durante dos horas consecutivas. Entre cada tren se tomaron registros de prueba. Al finalizar la serie se hizo una nueva curva estímulo-respuesta y se estudiaron nuevamente los impulsos pareados. La estimulación a 200 Hz produjo una potenciación de ambas variables estudiadas (pendiente de PPSE y amplitud de la espiga poblacional). Frecuencias interiores tuvieron efectos menos claros mientras que la estimulación a 400 Hz produjo un aumento de la espiga poblacional, pero una disminución de la pendiente del PPSE. Esto se manifestó también en cambios similares en las curvas estímulo-respuesta. La estimulación tetánica también modificó las relaciones a corto plazo provocando todas las frecuencias superiores a 10 Hz un predominio de los procesos de inhibición recíproca(AU)