RESUMO
Prolonged early-life seizures are associated with disruptions of affective and cognitive function. Postictal disturbances, temporary functional deficits that persist for hours to days after seizures, have not yet been thoroughly characterized. Here, we used kainic acid (KA) to induce status epilepticus (SE) in immature rats at three developmental stages (postnatal day (P) 15, 21, or 30) and subsequently assessed spatial learning and memory in a Barnes maze, exploratory behavior in an open field, and the spatiotemporal distribution of cell injury during the first 7-10 days of the postictal period. At 1 day post-SE, P15-SE rats showed no deficit in the Barnes maze but were hyperexploratory in an open field compared with their littermate controls. In contrast, P21- and P30-SE rats exhibited markedly impaired performance in the Barnes maze and exhibited significantly reduced open field exploration suggestive of anxiety-like behavior. These behavioral changes were transient in P15 rats but more persistent in P21 and enduring in P30 rats after KA-SE. The time course of behavioral deficits in P21 and P30 rats was temporally correlated with the presence of neuronal injury in the lateral septal nuclei, amygdala, and ventral subiculum/CA1, regions involved in modulation of the hypothalamic-pituitary-adrenal stress response.
Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Transtornos Mentais/etiologia , Convulsões/complicações , Convulsões/patologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Ácido Caínico/toxicidade , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Atividade Motora/fisiologia , Ratos , Ratos Long-Evans , Teste de Desempenho do Rota-Rod , Convulsões/induzido quimicamenteRESUMO
To appropriately adapt to constant sensory stimulation, neurons in the auditory system are tuned to various acoustic characteristics, such as center frequencies, frequency modulations, and their combinations, particularly those combinations that carry species-specific communicative functions. The present study asks whether such tunings extend beyond acoustic and communicative functions to auditory self-relevance and expertise. More specifically, we examined the role of the listening biography--an individual's long term experience with a particular type of auditory input--on perceptual-neural plasticity. Two groups of expert instrumentalists (violinists and flutists) listened to matched musical excerpts played on the two instruments (J.S. Bach Partitas for solo violin and flute) while their cerebral hemodynamic responses were measured using fMRI. Our experimental design allowed for a comprehensive investigation of the neurophysiology (cerebral hemodynamic responses as measured by fMRI) of auditory expertise (i.e., when violinists listened to violin music and when flutists listened to flute music) and nonexpertise (i.e., when subjects listened to music played on the other instrument). We found an extensive cerebral network of expertise, which implicates increased sensitivity to musical syntax (BA 44), timbre (auditory association cortex), and sound-motor interactions (precentral gyrus) when listening to music played on the instrument of expertise (the instrument for which subjects had a unique listening biography). These findings highlight auditory self-relevance and expertise as a mechanism of perceptual-neural plasticity, and implicate neural tuning that includes and extends beyond acoustic and communication-relevant structures.
Assuntos
Percepção Auditiva/fisiologia , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Música/psicologia , Desempenho Psicomotor/fisiologia , Reconhecimento Psicológico/fisiologia , Estimulação Acústica , Adolescente , Adulto , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Aprendizagem/fisiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/fisiologia , Testes Neuropsicológicos , Variações Dependentes do Observador , Adulto JovemRESUMO
BACKGROUND: Explosive synaptogenesis and synaptic pruning occur in the hippocampus during the first two weeks of postnatal life, coincident with a heightened susceptibility to seizures in rodents. To determine the temporal correlation between microglial development and age-dependent susceptibility and response to seizures, we quantified developmental changes in basal microglia levels and seizure-induced microglial activation in the hippocampus of Cx3Cr1(GFP /+) transgenic mice. METHODS: Basal levels of microglia were quantified in the hippocampi of Cx3Cr1(GFP /+) mice at P0, P5, P10, P15, P20, P25, P30, P40, and P60. Seizure susceptibility and seizure-induced microglial activation were assessed in response to febrile seizures (lipopolysaccharide followed by hyperthermia) and kainic acid-induced status epilepticus. RESULTS: The density of microglia within the hippocampus increased rapidly after birth, reaching a peak during the second week of life - the age at which the animals became most vulnerable to seizure triggers. In addition, this peak of microglial development and seizure vulnerability during the second postnatal week represented the time of maximal seizure-induced microglia activation. CONCLUSIONS: Overreactive innate immunity mediated by activated microglia may exacerbate acute injury to neuronal synapses and contribute to the long-term epileptogenic effects of early-life seizures. Anti-inflammatory therapy targeting excessive production of inflammatory mediators by activated microglia, therefore, may be an effective age-specific therapeutic strategy to minimize neuronal dysfunction and prevent increases in susceptibility to subsequent seizures in developing animals.