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1.
Neurobiol Learn Mem ; 167: 107135, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821882

RESUMO

Ubiquitination is involved in synaptic plasticity and memory, but the involvement of HECT E3 ligases in these processes has not yet been established. Here, we bilaterally infused heclin, a specific inhibitor of some of these ligases, into the dorsal hippocampus of male Wistar rats that were trained in a contextual fear conditioning. Heclin improved short-term memory, consolidation, retrieval, and reconsolidation when administered immediately post training, prior to testing, or after memory reactivation, respectively. In addition, it impaired memory extinction when administered prior to a long reactivation session. Heclin infusion was also tested for locomotor activity and anxiety-like behavior in a circular arena, but no effect was seen. Taken together, these results indicate that HECT E3 ligases are involved in the modulation of fear memory.


Assuntos
Condicionamento Clássico/fisiologia , Medo/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Ubiquitina-Proteína Ligases/fisiologia , Acrilamidas/administração & dosagem , Acrilamidas/farmacologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Extinção Psicológica/efeitos dos fármacos , Extinção Psicológica/fisiologia , Furanos/administração & dosagem , Furanos/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Rememoração Mental/efeitos dos fármacos , Rememoração Mental/fisiologia , Ratos Wistar , Ubiquitina-Proteína Ligases/antagonistas & inibidores
2.
Learn Mem ; 22(12): 584-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26572648

RESUMO

Despite the fact that the cannabinoid receptor type 1 (CB1R) plays a pivotal role in emotional memory processing in different regions of the brain, its function in the retrosplenial cortex (RSC) remains unknown. Here, using contextual fear conditioning in rats, we showed that a post-training intra-RSC infusion of the CB1R antagonist AM251 impaired, and the agonist CP55940 improved, long-term memory consolidation. Additionally, a post-reactivation infusion of AM251 enhanced memory reconsolidation, while CP55940 had the opposite effect. Finally, AM251 blocked extinction, whereas CP55940 facilitated it and maintained memory extinguished over time. Altogether, our data strongly suggest that the cannabinoid system of the RSC modulates emotional memory.


Assuntos
Córtex Cerebral/metabolismo , Extinção Psicológica/fisiologia , Medo/fisiologia , Consolidação da Memória/fisiologia , Receptor CB1 de Canabinoide/metabolismo , Animais , Agonistas de Receptores de Canabinoides/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Cateteres de Demora , Córtex Cerebral/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Cicloexanóis/farmacologia , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Masculino , Consolidação da Memória/efeitos dos fármacos , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos Wistar , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores
4.
Neuroscience ; 497: 14-29, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35314250

RESUMO

For decades, Izquierdo and colleagues contributed to building the notion that declarative memory requires different processes at the molecular and systems levels. This review aims to discuss part of Izquierdo's legacy, mainly but not exclusively that related to fear memory. First, some of the philosophical and evolutionary issues that arise from declarative memory definition are presented. Then, the underlying processes of declarative memory are depicted, discussing the formation, the nature and the progression of the memory trace in short-term and long-term memory, and describing the involvement of some molecular cascades in the hippocampal formation, mesocortex and frontal areas. Potential contributions to therapy or understanding cognitive processes are mentioned.


Assuntos
Medo , Córtex Pré-Frontal , Córtex Cerebral , Hipocampo , Memória de Longo Prazo
5.
Neurochem Res ; 36(2): 215-22, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21046237

RESUMO

Parkinson's disease (PD) is characterized by a progressive neurodegeneration in the substantia nigra and a striatal dopamine decrease. Striatal extracellular adenosine and ATP modulate the dopaminergic neurotransmission whereas guanosine has a protective role in the brain. Therefore, the regulation of their levels by enzymatic activity may be relevant to the clinical feature of PD. Here it was evaluated the extracellular nucleotide hydrolysis from striatal slices 4 weeks after a unilateral infusion with 6-OHDA into the medial forebrain bundle. This infusion increased ADP, AMP, and GTP hydrolysis by 15, 25, and 41%, respectively, and decreased GDP hydrolysis by 60%. There was no change in NTPDases1, 2, 3, 5, 6, and 5'-nucleotidase transcription. Dopamine depletion changes nucleotide hydrolysis and, therefore, alters the regulation of striatal nucleotide levels. These changes observed in 6-OHDA-lesioned animals may contribute to the symptoms observed in the model and provide evidence to indicate that extracellular purine hydrolysis is a key factor in understanding PD, giving hints for new therapies.


Assuntos
Adenina/metabolismo , Adrenérgicos/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Guanina/metabolismo , Oxidopamina/farmacologia , Doença de Parkinson/metabolismo , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Hidrolases Anidrido Ácido/genética , Hidrolases Anidrido Ácido/metabolismo , Animais , Modelos Animais de Doenças , Isoenzimas/metabolismo , Masculino , Feixe Prosencefálico Mediano/efeitos dos fármacos , Feixe Prosencefálico Mediano/metabolismo , Fosfatos/metabolismo , Ratos , Ratos Wistar
6.
Brain Res ; 1169: 112-9, 2007 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-17673185

RESUMO

Although vitamin A has been reported to be essential to brain homeostasis, some central nervous system (CNS)-associated deleterious effects may be induced by vitamin A or by its metabolites. In this work, we investigated the effects of acute and chronic vitamin A supplementation at therapeutic (1,000 or 2,500 IU/kg/day) or excessive (4,500 or 9,000 IU/kg/day) doses on the redox state of the rat striatum. We found a 1.8- to 2.7-fold increase of lipid peroxidation in the striatum after acute or chronic supplementation (TBARS method). Therapeutic doses induced a 1.6- to 2.2-fold increase of protein carbonylation (dinitrophenylhydrazine (DNPH) derivatization). Vitamin A supplementation induced a 1.2- to 1.4-fold decrease of protein thiol content acutely and chronically. Superoxide dismutase (SOD) activity, assessed through the inhibition of epinephrine's autoxidation, was increased in a dose-dependent manner chronically. Acutely, both therapeutic and excessive vitamin A doses induced a 1.8- to 2.2-fold decrease of catalase (CAT) activity, as determined through the rate of decrease of hydrogen peroxide (H(2)O(2)). Glutathione peroxidase (GPx) activity did not change in this experimental model. Some vitamin A doses decreased the non-protein thiol content only chronically. Vitamin A supplementation decreased the striatal non-enzymatic antioxidant defenses (TRAP assay). Furthermore, our results show that vitamin A supplementation impaired the SOD/CAT ratio. Moreover, we observed a 1.6- to 2.0-fold decrease of locomotion and exploration in an open field after vitamin A supplementation. Therefore, our results suggest that vitamin A supplementation induces oxidative stress in the rat striatum and that it may be related to a metabolic impairment in such brain area.


Assuntos
Doenças dos Gânglios da Base/induzido quimicamente , Encefalopatias Metabólicas/induzido quimicamente , Corpo Estriado/efeitos dos fármacos , Discinesia Induzida por Medicamentos/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Vitamina A/toxicidade , Animais , Antioxidantes/metabolismo , Doenças dos Gânglios da Base/metabolismo , Doenças dos Gânglios da Base/fisiopatologia , Encefalopatias Metabólicas/metabolismo , Encefalopatias Metabólicas/fisiopatologia , Catalase/efeitos dos fármacos , Catalase/metabolismo , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Esquema de Medicação , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Oxirredução , Estresse Oxidativo/fisiologia , Carbonilação Proteica/efeitos dos fármacos , Carbonilação Proteica/fisiologia , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
7.
Neurotoxicology ; 28(6): 1191-9, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17727954

RESUMO

Vitamin A participates in the maintenance of normal hippocampal function during embryonic and postnatal stages of the vertebrate life. Some works demonstrated that vitamin A metabolites impair learning and induce a depression-like behavior in mice, among other effects. Since vitamin A has prooxidant effects on other experimental models, we decided to investigate whether vitamin A can induce oxidative stress in the adult rat hippocampus. We analyzed the sub acute effects of therapeutic (1000 and 2500 I.U./kg) or excessive (4500 and 9000 I.U./kg) vitamin A doses on the hippocampal redox state, as well as on levels of anxiety, and locomotory and exploratory activity. Vitamin A supplementation induced lipid peroxidation, protein carbonylation, and oxidation of the protein thiol content in the rat hippocampus in all periods analyzed. Increased superoxide dismutase (SOD) activity and decreased catalase (CAT) activity were also observed, which gives rise to an imbalance in the principal cellular enzymatic antioxidant system. Then, our results show, for the first time, that vitamin A induced oxidative stress in the adult rat hippocampus, is anxiogenic, and decreases locomotion in and exploration of an open field.


Assuntos
Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Vitamina A/toxicidade , Vitaminas/toxicidade , Envelhecimento/metabolismo , Animais , Catalase/metabolismo , Relação Dose-Resposta a Droga , Glutationa Peroxidase , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Oxirredução , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo
8.
Behav Brain Res ; 287: 226-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25835320

RESUMO

Neuroimmune signalling underlies addiction and comorbid depression. Clinical observations indicate that infections and chronic lesions are more frequent in drug users and elevated inflammatory states are evident in cocaine dependents. Therefore, lipopolysaccharide (LPS) and inflammatory cytokines represent an important tool for the investigation of sickness, depressive illness and addiction behaviour. A major component of addiction is the progressive and persistent increase in locomotor activity after repeated drug administration and even prolonged periods of abstinence. The aim of this study was to investigate the response of locomotor sensitization when a non-sensitizing dose of cocaine is paired with a systemic inflammatory stimulus. LPS and cocaine were administered intraperitonealy in young-adult male C57bl/6 mice during a 5-day acquisition phase. After a 48-h withdrawal period all groups were challenged with cocaine to evaluate locomotor expression. During the acquisition phase, the LPS-treated groups displayed characteristic hypolocomotion related to sickness behaviour. The low dose of cocaine did not increase the distance travelled, characterizing a non-sensitization dose. Groups that received both LPS and cocaine did not display hypolocomotion, indicating that cocaine might counteract hypolocomotion sickness behaviour. Moreover, during challenge, only these animals expressed locomotor sensitization. Our results indicate that LPS could facilitate the expression of locomotor sensitization in mice and that the immune system may modulate cocaine-induced sensitization.


Assuntos
Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Lipopolissacarídeos/toxicidade , Locomoção/efeitos dos fármacos , Locomoção/imunologia , Animais , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Distribuição Aleatória
9.
Behav Brain Res ; 128(2): 121-7, 2002 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-11796157

RESUMO

Compelling evidence has indicated the involvement of extracellular ATP and adenosine in the mechanisms of synaptic plasticity and memory formation. In the present study, adult rats were trained in a step-down inhibitory avoidance task (IA) or submitted to isolated foot-shock (IF) (0.4 mA) before measuring ectonucleotidase activities in the synaptosomes of the anterior and posterior cingulate cortex (AC and PC, respectively) and the medial precentral area (Fr2). IA increased ATP and ADP hydrolysis immediately after training in the synaptosomes of PC and AC, respectively, (P<0.05). Foot-shock (independent of occurring during IA or IF) increased ATP hydrolysis in synaptosomes of AC and Fr2 immediately after application and decreased AIP hydrolysis in AC 90 min after application (P<0.05). Foot-shock (independent of occurring during IA or IF) increased ATP hydrolysis in PC immediately and 90 min after application, and in Fr2, but only immediately after application (P<0.05). These results suggest that the ectonucleotidase pathway responds to a mild foot-shock in AC, PC and Fr2 and may be involved in memory consolidation of step-down inhibitory avoidance in the cingulate cortex.


Assuntos
Aprendizagem da Esquiva/fisiologia , Córtex Cerebral/enzimologia , Nucleotidases/metabolismo , Córtex Pré-Frontal/enzimologia , Estresse Psicológico/enzimologia , Estresse Psicológico/psicologia , Sinaptossomos/enzimologia , Adenosina/biossíntese , Adenosina/fisiologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Eletrochoque , Hidrólise , Masculino , Memória/fisiologia , Ratos , Ratos Wistar , Frações Subcelulares/enzimologia
10.
Eur J Pharmacol ; 437(3): 151-4, 2002 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-11890903

RESUMO

Male Wistar rats were bilaterally implanted with indwelling cannulae in the caudal region of the posterior cingulate cortex. After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock) and received, immediately after training, a 0.5-microl infusion of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA; 1, 50 or 100 nM) or of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1, 25 or 50 nM). Animals were tested twice, 1.5 h and, again, 24 h after training, in order to examine the effects of these agents on short- and long-term memory, respectively. Only 50-nM DPCPX was effective in altering memory, promoting a facilitation. These results suggest that adenosine A1 receptors in the posterior cingulate cortex inhibit memory consolidation in a way that their blockade facilitates memory for inhibitory avoidance in rats.


Assuntos
Adenosina/análogos & derivados , Giro do Cíngulo/efeitos dos fármacos , Memória/efeitos dos fármacos , Antagonistas de Receptores Purinérgicos P1 , Xantinas/farmacologia , Adenosina/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Relação Dose-Resposta a Droga , Giro do Cíngulo/metabolismo , Masculino , Ratos , Receptores Purinérgicos P1/fisiologia , Retenção Psicológica/efeitos dos fármacos
11.
Exp Neurol ; 224(1): 188-96, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20303347

RESUMO

In the present study we investigated the effect of in vivo intrastriatal injection of quinolinic acid (QA) on cytoskeletal proteins in astrocytes and neurons of young rats at early stage (30 min) after infusion. QA (150 nmoles/0.5 microL) significantly increased the in vitro phosphorylation of the low molecular weight neurofilament subunit (NFL) and the glial fibrillary acidic protein (GFAP) of neurons and astrocytes, respectively. This effect was mediated by cAMP-dependent protein kinase A (PKA), protein kinase C (PKC) and Ca(2+)/calmodulin-dependent protein kinase II (PKCaMII). In contrast, mitogen activated protein kinases were not activated by QA infusion. Furthermore, the specific N-methyl-D-aspartate (NMDA) antagonist MK-801 (0.25 mg/kg i.p), the antioxidant L-NAME (60 mg\kg\day), and diphenyldisselenide (PheSe)(2) (0.625 mg\kg\day) injected prior to QA infusion totally prevented QA-induced cytoskeletal hyperphosphorylation. We also observed that QA-induced hyperphosphorylation was targeted at the Ser55 phosphorylating site on NFL head domain, described as a regulatory site for NF assembly in vivo. This effect was fully prevented by MK801, by the PKA inhibitor H89 and by (PheSe)(2), whereas staurosporine (PKC inhibitor) only partially prevented Ser55 phosphorylation. The PKCaMII inhibitor (KN93) and the antioxidant L-NAME failed to prevent the hyperphosphorylation of Ser55 by QA infusion. Therefore, we presume that QA-elicited hyperphosphorylation of the neural cytoskeleton, and specially of NFLSer55, achieved by intrastriatal QA injection could represent an early step in the pathophysiological cascade of deleterious events exerted by QA in rat striatum. Our observations also indicate that NMDA-mediated Ca(2+) events and oxidative stress may be related to the altered protein cytoskeleton hyperphosphorylation observed with important implications for brain function.


Assuntos
Astrócitos/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neurônios/efeitos dos fármacos , Ácido Quinolínico/farmacologia , Análise de Variância , Animais , Astrócitos/metabolismo , Western Blotting , Corpo Estriado/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Maleato de Dizocilpina/farmacologia , Inibidores Enzimáticos/farmacologia , Microinjeções , NG-Nitroarginina Metil Éster/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
12.
Neurochem Int ; 56(6-7): 753-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20172010

RESUMO

Essential omega-3 polyunsaturated fatty acids (omega3) are crucial to brain development and function, being relevant for behavioral performance. In the present study we examined the influence of dietary omega3 in the development of the glutamatergic system and on behavior parameters in rats. Female rats received isocaloric diets, either with omega3 (omega3 group) or a omega3 deficient diet (D group). In ontogeny experiments of their litters, hippocampal immunocontent of ionotropic NMDA and AMPA glutamatergic receptors subunits (NR2 A\B and GluR1, respectively) and the alpha isoform of the calcium-calmodulin protein kinase type II (alphaCaMKII) were evaluated. Additionally, hippocampal [(3)H]glutamate binding and uptake were assessed. Behavioral performance was evaluated when the litters were adult (60 days old), through the open-field, plus-maze, inhibitory avoidance and flinch-jump tasks. The D group showed decreased immunocontent of all proteins analyzed at 02 days of life (P2) in comparison with the omega3 group, although the difference disappeared at 21 days of life (except for alphaCaMKII, which content normalized at 60 days old). The same pattern was found for [(3)H]glutamate binding, whereas [(3)H]glutamate uptake was not affected. The D group also showed memory deficits in the inhibitory avoidance, increased in the exploratory pattern in open-field, and anxiety-like behavior in plus-maze. Taken together, our results suggest that dietary omega3 content is relevant for glutamatergic system development and for behavioral performance in adulthood. The putative correlation among the neurochemical and behavioral alterations caused by dietary omega3 deficiency is discussed.


Assuntos
Comportamento Animal/fisiologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Insaturados/deficiência , Ácido Glutâmico/fisiologia , Sinapses/fisiologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/análise , Ácidos Graxos Ômega-3/fisiologia , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/química , Hipocampo/metabolismo , Lactação , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Wistar , Receptores de AMPA/análise , Receptores de N-Metil-D-Aspartato/análise , Sinaptossomos/química , Trítio
13.
Neurochem Res ; 33(3): 378-83, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17712631

RESUMO

Vitamin A is known to regulate some central nervous system (CNS)-associated functions. Vitamin A at high doses has been demonstrated to be beneficial in the treatment of some diseases, for instance acute promyelocytic leukemia. However, vitamin A and its naturally occurring metabolites (retinoids) are known to alter neuronal function, inducing behavioral disorders. Here we provide an evidence to indicate that vitamin A supplementation, at both therapeutic and excessive doses, induces oxidative stress in the rat substantia nigra. Vitamin A supplementation induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups, as well as change in catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity. Surprisingly, locomotory and exploratory activity of rats were decreased after acute and chronic vitamin A supplementation. Therefore, we may conclude from our results that vitamin A supplementation is prooxidant to the rat substantia nigra and effective in altering behavior.


Assuntos
Comportamento Exploratório/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substância Negra/metabolismo , Vitamina A/uso terapêutico , Animais , Biomarcadores , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Carbonilação Proteica/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitamina A/administração & dosagem
14.
J Neurophysiol ; 93(3): 1450-67, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15496491

RESUMO

In primary sensory cortices, neuronal responses to a stimulus presented as part of a rapid sequence often differ from responses to an isolated stimulus. It has been reported that sequential stimulation of two whiskers produces facilitatory modulations of barrel cortex neuronal responses. These results are at odds with the well-known suppressive interaction that has been usually described. Herein, we have examined the dependency of response modulation on the spatiotemporal pattern of stimulation by varying the spatial arrangement of the deflected vibrissae, the temporal frequency of stimulation, and the time interval between whisker deflections. Extracellular recordings were made from primary somatosensory cortex of anesthetized rats. Two contralateral whiskers were stimulated at 0.5 and 8 Hz at intervals ranging from 0 to +/-30 ms. Response interactions were assessed during stimulation of the principal and adjacent whiskers, first from the same row and second from the same arc. When tested at 0.5 Hz, 59% of single units showed a statistically significant suppressive interaction, whereas response facilitation was found in only 6% of cells. In contrast, at 8 Hz, a significant supralinear summation was observed in 19% of the cells, particularly for stimulations along an arc rather than along a row. Multi-unit recordings showed similar results. These observations indicate that most of the interactions in the barrel cortex during two-whisker stimulation are suppressive. However, facilitation can be revealed when stimuli are applied at a physiological frequency and could be the basis for internal representations of the spatiotemporal pattern of the stimulus.


Assuntos
Potenciais de Ação/fisiologia , Inibição Neural/fisiologia , Neurônios Aferentes/fisiologia , Córtex Somatossensorial/citologia , Vibrissas/inervação , Vibrissas/fisiologia , Análise de Variância , Animais , Relação Dose-Resposta à Radiação , Lateralidade Funcional/fisiologia , Masculino , Estimulação Física/métodos , Ratos , Ratos Wistar , Tempo de Reação/fisiologia , Córtex Somatossensorial/fisiologia , Fatores de Tempo , Vibrissas/citologia
15.
Hippocampus ; 12(4): 551-60, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12201640

RESUMO

Information storage in the brain is a temporally graded process involving different memory types or phases. It has been assumed for over a century that one or more short-term memory (STM) processes are involved in processing new information while long-term memory (LTM) is being formed. Because brain-derived neutrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in the adult hippocampus, we examined the role of BDNF in STM and LTM formation of a hippocampal-dependent one-trial fear-motivated learning task in rats. Using a competitive RT-PCR quantitation method, we found that inhibitory avoidance training is associated with a rapid and transient increase in BDNF mRNA expression in the hippocampus. Bilateral infusions of function-blocking anti-BDNF antibody into the CA, region of the dorsal hippocampus decreased extracellular signal-regulated kinase 2 (ERK2) activation and impaired STM retention scores. Inhibition of ERK1/2 activation by PD098059 produced similar effects. In contrast, intrahippocampal administration of recombinant human BDNF increased ERK1/2 activation and facilitated STM. The infusion of anti-BDNF antibody impaired LTM when given 15 min before or 1 and 4 hr after training, but not at 0 or 6 hr posttraining, indicating that two hippocampal BDNF-sensitive time windows are critical for LTM formation. At the same time points, PD098059 produced no LTM deficits. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of an inhibitory avoidance learning. Additionally, they suggest that this requirement involves ERK1/2-dependent and -independent mechanisms.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Hipocampo/fisiologia , Memória de Curto Prazo/fisiologia , Memória/fisiologia , Animais , Anticorpos/administração & dosagem , Aprendizagem da Esquiva/fisiologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/imunologia , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Esquema de Medicação , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Medo/fisiologia , Flavonoides/farmacologia , Aprendizagem/fisiologia , Masculino , Memória/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteínas Recombinantes/farmacologia , Retenção Psicológica/fisiologia , Fatores de Tempo
16.
Neurochem Res ; 28(8): 1181-6, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12834257

RESUMO

Early restriction of nutrients during the perinatal period has marked repercussions on CNS ontogeny, leading to impaired functions. This study investigated the effects of pre- and postnatal (up to 75 days) undernutrition (diet: 8% protein; normonourished group: 25% protein) on some glutamatergic and behavioral parameters of rats. Undernutrition reduced: (i) seizures caused by ICV quinolinic acid (QA) administration; (ii) Na-independent [3H]glutamate binding in cell plasma membranes of cerebral cortex, and (ii) basal [3H]glutamate release from synaptosomal preparation. Behavioral parameters related to locomotion, anxiety, or memory were not affected. These results indicate that our model of undernutrition decreased the sensitivity to QA as convulsing agent and point to some putative glutamatergic parameters involved in this effect.


Assuntos
Encéfalo/metabolismo , Ácido Glutâmico/metabolismo , Distúrbios Nutricionais/metabolismo , Animais , Comportamento Animal , Masculino , Ratos , Ratos Wistar
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