RESUMO
Evidence that protein synthesis inhibitors induce amnesia in a variety of species and learning paradigms indicates that the consolidation of newly acquired information into stable memories requires the synthesis of new proteins. Because extinction of a response also requires acquisition of new information, extinction, like original learning, would be expected to require protein synthesis. The present experiments examined the involvement of protein synthesis in the hippocampus in the extinction of a learned fear-based response known to involve the hippocampus. Rats were trained in a one-trial inhibitory avoidance task in which they received footshock after stepping from a small platform to a grid floor. They were then given daily retention tests without footshock. The inhibitory response (e.g., remaining on the platform) gradually extinguished with repeated testing over several days. Footshock administered in a different context, instead of a retention test, prevented the extinction. Infusions of the protein synthesis inhibitor anisomycin (80 microg) into the CA1 region of the hippocampus (bilaterally) 10 min before inhibitory avoidance training impaired retention on all subsequent tests. Anisomycin infused into the hippocampus immediately after the 1st retention test blocked extinction of the response. Infusions administered before the 1st retention test induced a temporary (i.e., 1 day) reduction in retention performance and blocked subsequent extinction. These findings are consistent with other evidence that anisomycin blocks both the consolidation of original learning and extinction.
Assuntos
Anisomicina/farmacologia , Extinção Psicológica/efeitos dos fármacos , Medo/psicologia , Hipocampo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Inibidores da Síntese de Proteínas/farmacologia , Animais , Hipocampo/metabolismo , Aprendizagem , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
This article is a transcription of an electronic symposium in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the neurobiology of emotion. Four basic questions were debated: 1) What are the most critical issues/questions in the neurobiology of emotion? 2) What do we know for certain about brain processes involved in emotion and what is controversial? 3) What kinds of research are needed to resolve these controversial issues? 4) What is the relationship between learning, memory and emotion? The focus was on the existence of different neural systems for different emotions and the nature of the neural coding for the emotional states. Is emotion the result of the interaction of different brain regions such as the amygdala, the nucleus accumbens, or the periaqueductal gray matter or is it an emergent property of the whole brain neural network? The relationship between unlearned and learned emotions was also discussed. Are the circuits of the former the underpinnings of the latter? It was pointed out that much of what we know about emotions refers to aversively motivated behaviors, like fear and anxiety. Appetitive emotions should attract much interest in the future. The learning and memory relationship with emotions was also discussed in terms of conditioned and unconditioned stimuli, innate and learned fear, contextual cues inducing emotional states, implicit memory and the property of using this term for animal memories. In a general way it could be said that learning modifies the neural circuits through which emotional responses are expressed.
Assuntos
Encéfalo/fisiologia , Emoções/fisiologia , Aprendizagem/fisiologia , Neurobiologia , Tonsila do Cerebelo/fisiologia , Animais , Ansiedade , Medo/fisiologia , Humanos , Memória/fisiologia , Substância Cinzenta Periaquedutal/fisiologiaRESUMO
This article is a transcription of an electronic symposium in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the neurobiology of emotion. Four basic questions were debated: 1) What are the most critical issues/questions in the neurobiology of emotion? 2) What do we know for certain about brain processes involved in emotion and what is controversial? 3) What kinds of research are needed to resolve these controversial issues? 4) What is the relationship between learning, memory and emotion? The focus was on the existence of different neural systems for different emotions and the nature of the neural coding for the emotional states. Is emotion the result of the interaction of different brain regions such as the amygdala, the nucleus accumbens, or the periaqueductal gray matter or is it an emergent property of the whole brain neural network? The relationship between unlearned and learned emotions was also discussed. Are the circuits of the former the underpinnings of the latter? It was pointed out that much of what we know about emotions refers to aversively motivated behaviors, like fear and anxiety. Appetitive emotions should attract much interest in the future. The learning and memory relationship with emotions was also discussed in terms of conditioned and unconditioned stimuli, innate and learned fear, contextual cues inducing emotional states, implicit memory and the property of using this term for animal memories. In a general way it could be said that learning modifies the neural circuits through which emotional responses are expressed
Assuntos
Humanos , História do Século XX , Animais , Encéfalo/fisiologia , Emoções/fisiologia , Aprendizagem/fisiologia , Neurobiologia , Tonsila do Cerebelo/fisiologia , Ansiedade , Medo/fisiologia , Memória/fisiologia , Neurobiologia/história , Substância Cinzenta Periaquedutal/fisiologiaRESUMO
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.
Assuntos
Encéfalo/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Humanos , Memória de Curto Prazo/fisiologiaRESUMO
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
Assuntos
Aprendizagem/fisiologia , Memória/fisiologia , Tonsila do Cerebelo , Hipocampo , Memória de Curto Prazo/fisiologiaRESUMO
Recent findings have significantly advanced our understanding the mechanisms of memory formation. Most of these advances stemmed from behavioural pharmacology research involving, particularly, the localized infusion of drugs with specific molecular actions into specific brain regions. This approach has revealed brain structures involved in different memory types and the main neurotransmitter systems and sequence of metabolic cascades that participate in memory consolidation. Biochemical studies and, in several cases, studies of genetically manipulated animals, in which receptors or enzymes affected by the various drugs were absent or overexpressed, have complemented the pharmacological research. Although most studies have concentrated on the involvement of the hippocampus, many have also investigated the entorhinal cortex, other regions of the cortex, and the amygdala. Behavioural pharmacology has been of crucial importance in establishing the major neurohumoral and hormonal systems involved in the modulation of memory formation. These systems act on specific steps of memory formation in the hippocampus and in the entorhinal, parietal, and cingulate cortex. A specialized system mediated by the basolateral amygdaloid nucleus, and involving several neuromodulatory systems, is activated by emotional arousal and serves to regulate memory formation in other brain regions. The core mechanisms involved in the formation of explicit (declarative) memory are in many respects similar to those of long-term potentiation (LTP), particularly in the hippocampus. However, there are also important differences between memory formation and LTP. Memory formation involves numerous modulatory influences, the co-participation of various brain regions other than the hippocampus, and some properties that are specific to memory and absent in LTP (i.e. flexibility of response). We discuss the implications of these similarities and differences for understanding the neural bases of memory.
Assuntos
Comportamento Animal/efeitos dos fármacos , Comportamento/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Humanos , Potenciação de Longa Duração/efeitos dos fármacosRESUMO
Extensive evidence indicates that benzodiazepine receptors in the amygdala are involved in regulating memory consolidation. Recent findings indicate that many other drugs and hormones influence memory through selective activation of the basolateral amygdala nucleus (BLA). This experiment examined whether the memory-modulatory effect of flumazenil, a benzodiazepine receptor antagonist, selectively involves the BLA. Bilateral microinfusions of flumazenil (12 nmol in 0.2 microl) into the BLA of rats administered immediately after training in an inhibitory avoidance task significantly enhanced 48-h retention performance whereas infusions into the central nucleus were ineffective. These findings indicate that the BLA is selectively involved in mediating flumazenil's influence on memory storage and are thus consistent with extensive evidence indicating that the BLA is involved in regulating memory consolidation.
Assuntos
Tonsila do Cerebelo/fisiologia , Aprendizagem da Esquiva/fisiologia , Flumazenil/farmacologia , Antagonistas de Receptores de GABA-A , Memória/fisiologia , Receptores de GABA-A/fisiologia , Tonsila do Cerebelo/patologia , Análise de Variância , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Estatísticas não ParamétricasRESUMO
Infusion of the calcium-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-62 (3.5 ng/side) 0 h after training into rat hippocampus CA1 or amygdala has been known for years to cause retrograde amnesia for step-down inhibitory avoidance. On the other hand, drugs that indirectly stimulate protein kinase A (PKA) (8-Br-cAMP, 1.25 microg/side; norepinephrine, 0.3 microg/side; the dopamine D1 receptor agonist, SKF38393, 7.5 microg/side) infused 3 h posttraining into CA1 but not amygdala markedly facilitate retention of this task. Here we find that 8-Br-cAMP, norepinephrine, or SKF38393 given 3 h posttraining into rat CA1 reverses the amnestic effect of KN-62 given into the amygdala 0 h after training, but not that of KN-62 given into CA1 0 h posttraining. The findings bear on the participation of CaMKII and of the cAMP/PKA cascade in memory processes in the hippocampus and the amygdala. Both cascades have been proposed to play a role in memory: CaMKII in the early phase and PKA in the transition between the early phase and long-term memory. Clearly, in CA1, both cascades are involved and are crucial, and the CaMKII cascade must precede the PKA cascade. In contrast, in the amygdala, only the CaMKII cascade is active, and it does not play a central role in memory, inasmuch as its deleterious effect may be fully recovered by stimulation of the PKA cascade in the hippocampus. This further supports the contention that the hippocampus is essential for memory formation of this task, as it is for many others, whereas the amygdala appears to play instead an early modulatory role.
Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Tonsila do Cerebelo/efeitos dos fármacos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , AMP Cíclico/metabolismo , Inibidores Enzimáticos/farmacologia , Hipocampo/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Retenção Psicológica/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Injeções , Masculino , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacosRESUMO
These experiments examined the effects of N-methyl-D-aspartate (NMDA)-induced lesions of the amygdala and insular cortex induced 1 week after rats were trained on a footshock motivated escape task in a two-compartment runway. In the first experiment, male rats were given 10 training trials and, 1 week later, received microinjections of a buffer solution or NMDA into either the insular cortex (IC) or the amygdala (AM). In an inhibitory avoidance retention test 1 week after the microinjections, the retention latencies (i.e., latencies to enter the compartment where shock had been delivered) of both the AM- and "IC-lesioned" groups were significantly lower than those of the buffer-injected groups. Additionally, in comparison with the buffer controls, rats in the two lesioned groups made significantly more crossings between the two compartments during the retention test. In a second experiment, male rats were given 1, 10, or 20 escape training trials 1 week before receiving either sham or NMDA lesions in the IC. The retention test was given 1 week after microinjection. Those sham or lesioned animals that were given only one training trial did not demonstrate retention. Both lesioned groups given 10 or 20 training trials were significantly disrupted on both the step-through latencies, and the number of crossings between the two compartments. The retention-impairing effects of NMDA-induced lesions were slightly attenuated in the group given 20 escape training trials. The findings provide additional evidence that the AM and the IC are involved in regulating the long-term retention of aversively motivated training.
Assuntos
Tonsila do Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Retenção Psicológica , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Comportamento Animal , Córtex Cerebral/efeitos dos fármacos , Masculino , N-Metilaspartato/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
It is well known that systemically administered benzodiazepines (BZDs) induce anterograde amnesia in a variety of learning tasks. BZs effects are mediated through the GABAA complex by enhancing GABA-induced synaptic inhibition. As the GABAergic system in the amygdaloid complex (AC) is a site of action for the anxiolytic effects of BZs, such findings suggest that BZs may also influence memory through the amygdala. The present report summarizes a recent series of experiments designed to examine this implication. In a first experiment rats received either sham or bilateral AC lesion using N-methyl-D-aspartic acid (NMDA). One week later, animals were trained on an inhibitory avoidance task and tested 48 h later. Diazepam (DZP; 1.0 and 2.0 mg/kg, i.p.) or vehicle was injected 30 min prior to acquisition. The results demonstrate that DZP-induced retention deficits was blocked in rats with AC lesions. In a second experiment, in an attempt to localize the site of BZDs amnestic action in the AC, we tested the effects of DZP in rats with bilateral ibotenic acid-induced lesions of central (CE), lateral (LAT) or basolateral (BL) amygdala nuclei. The results shown that retention was impaired in animals with CE and LAT lesions but not in animals with BL lesions. In a third experiment we tested the effects of DZP microinjections in different nuclei of the AC on retention performance of rats trained in an avoidance task. The results demonstrate that DZP microinjection prior training in the BL/LAT, but not CE nuclei produce anterograde amnesia.(ABSTRACT TRUNCATED AT 250 WORDS)