The Journal of neuroscience : the official journal of the Society for Neuroscience
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Comparative Study
Developmental changes in NMDA neurotoxicity reflect developmental changes in subunit composition of NMDA receptors.
Excitotoxicity is generally studied in dissociated neurons, cultured hippocampal slices, or intact animals. However, the requirements of dissociated neurons or cultured slices to use prenatal or juvenile rats seriously limit the advantages of these systems, whereas the complexity of intact animals prevents detailed molecular investigations. In the present experiments, we studied developmental changes in NMDA neurotoxicity in acute hippocampal slices with lactate dehydrogenase (LDH) release in medium, propidium iodide (PI) uptake, and Nissl staining as markers of cell damage. ⋯ NMDA-induced changes in Nissl staining were also different in slices from young and adult rats and blocked by NR2B but not NR2A antagonists. In contrast to NMDA treatment, oxygen/glucose deprivation (OGD) induced neurotoxicity in slices from both young and adult rats, although OGD-induced toxicity was attenuated by MK-801 only in slices from young rats. Our results are consistent with the idea that NMDA-mediated toxicity is caused by activation of NR2B- but not NR2A-containing NMDA receptors leading to calpain activation and that developmental changes in NMDA toxicity reflect developmental changes in NMDA receptor subunit composition.
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Comparative Study
An epilepsy mutation in the sodium channel SCN1A that decreases channel excitability.
Mutations in three voltage-gated sodium channel genes, SCN1A, SCN2A, and SCN1B, and two GABAA receptor subunit genes, GABRG2 and GABRD, have been identified in families with generalized epilepsy with febrile seizures plus (GEFS+). A novel mutation, R859C, in the Nav1.1 sodium channel was identified in a four-generation, 33-member Caucasian family with a clinical presentation consistent with GEFS+. The mutation neutralizes a positively charged arginine in the domain 2 S4 voltage sensor of the Nav1.1 channel alpha subunit. ⋯ When the mutation was placed in the rat Nav1.1 channel and expressed in Xenopus oocytes, the mutant channel displayed a positive shift in the voltage dependence of sodium channel activation, slower recovery from slow inactivation, and lower levels of current compared with the wild-type channel. Computational analysis suggests that neurons expressing the mutant channel have higher thresholds for firing a single action potential and for firing multiple action potentials, along with decreased repetitive firing. Therefore, this mutation should lead to decreased neuronal excitability, in contrast to most previous GEFS+ sodium channel mutations, which have changes predicted to increase neuronal firing.
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Comparative Study
Amygdala activity is associated with the successful encoding of item, but not source, information for positive and negative stimuli.
It has been debated whether the link between amygdala activity and subsequent memory is equally strong for positive and negative information. Moreover, it has been unclear whether amygdala activity at encoding corresponds with enhanced memory for all contextual aspects of the presentation of an emotional item, or whether amygdala activity primarily enhances memory for the emotional item itself. In the present functional magnetic resonance imaging study, participants encoded positive and negative stimuli while performing one of two tasks (judgment of animacy or commonness). ⋯ Regardless of the emotional content of the items, activity in the entorhinal cortex corresponded with subsequent memory for the item but not with memory for the task performed, whereas hippocampal activity corresponded with subsequent memory for the task performed. These results are the first to demonstrate that the amygdala can be equally engaged during the successful encoding of positive and negative items but that its activity does not facilitate the encoding of all contextual elements present during an encoding episode. The results further suggest that dissociations within the medial temporal lobe sometimes noted for nonemotional information (i.e., activity in the hippocampus proper leading to later memory for context, and activity in the entorhinal cortex leading to later memory for an item but not its context) also hold for emotional information.