The Journal of neuroscience : the official journal of the Society for Neuroscience
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Neurons classified as nociceptors are dependent on nerve growth factor (NGF) during embryonic development, but a large subpopulation lose this dependence during embryonic and postnatal times and become responsive to the transforming growth factor beta family member, glial cell line-derived growth factor (GDNF). To elucidate the functional properties of GDNF-dependent nociceptors and distinguish them from nociceptors that retain NGF dependence, the cellular and physiologic properties of sensory neurons of wild-type and transgenic mice that overexpress GDNF in the skin (GDNF-OE) were analyzed using a skin, nerve, dorsal root ganglion, and spinal cord preparation, immunolabeling, and reverse transcriptase-PCR assays. Although an increase in peripheral conduction velocity of C-fibers in GDNF-OE mice was measured, other electrophysiological properties, including resting membrane potential and somal action potentials, were unchanged. ⋯ However, no change was observed in heat thresholds for the same population of cells. The increase in mechanical sensitivity was found to correlate with significant increases in acid-sensing ion channels 2A and 2B and transient receptor potential channel A1, which are thought to contribute to detection of mechanical stimuli. These data indicate that enhanced expression of GDNF in the skin can change mechanical sensitivity of IB4-positive nociceptive afferents and that this may occur through enhanced expression of specific types of channel proteins.
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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.