The Journal of neuroscience : the official journal of the Society for Neuroscience
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To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86-88% in lamina II neurons. ⋯ However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury.
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The six-layered neocortex is composed of excitatory projection neurons and inhibitory interneurons. Recent studies have established separate embryological origins for these two cellular populations. However, it remains uncertain how interneurons arising from the subcortical ganglionic eminences are able to participate in the orderly stratification of the cortical layers. ⋯ Both early- and late-born progenitors were able to switch their fates in the new environment, and, similar to projection neurons, fate-switching was dependent on progenitor receptivity to environmental cues during their last round of cell division. Our data also demonstrate, for the first time, that interneuron-layering cues are present within the medial ganglionic eminence, suggesting that, before the commencement of long-distance tangential migration, interneurons are already specified with respect to their future layer addresses. So, although the generation of diverse neuronal phenotypes in separate locations is an effective strategy to pursue separate developmental programs, our results indicate that excitatory and inhibitory neurons share similar mechanisms for integrating sequentially born neurons from two places into a single layered structure.
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Comparative Study
Fatigue and paradoxical enhancement of heat response in C-fiber nociceptors from cross-modal excitation.
Fatigue refers to the decrement of response seen with repeated stimulation and is a prominent attribute of nociceptors. Whether fatigue in nociceptors involves transduction, spike initiation, or conduction mechanisms is unknown. We investigated systematically how electrical, mechanical, and heat conditioning stimuli (eCS, mCS, hCS) affected the subsequent response to a test-heat stimulus applied 5 sec later to the receptive field of cutaneous nociceptors. ⋯ The paradoxical enhancement after the mCS probably results from temporal summation of generator potentials produced by mechanical and heat stimulation and suggests that the time constant of the generator potential is on the order of seconds. Concurrent enhancement-fatigue effects may also explain why fatigue was less after the mCS than the eCS. The dependency of recovery from fatigue on the modality of the CS suggests that fatigue results from transduction-spike initiation mechanisms.
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Hair cell loss in the mammalian cochlea is irreversible and results in permanent hearing loss. Math1, the basic helix-loop-helix transcription factor homolog of the Drosophila atonal gene, is a positive regulator of hair cell differentiation during cochlear development. Developing hair cells express Math1, and nonsensory cells do not. ⋯ Math1 overexpression leads to the appearance of immature hair cells in the organ of Corti and new hair cells adjacent to the organ of Corti in the interdental cell, inner sulcus, and Hensen cell regions. Axons are extended from the bundle of auditory nerve toward some of the new hair cells, suggesting that the new cells attract auditory neurons. We conclude that nonsensory cells in the mature cochlea retain the competence to generate new hair cells after overexpression of Math1 in vivo and that Math1 is necessary and sufficient to direct hair cell differentiation in these mature nonsensory cells.
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In recent years, attention has been given to the interaction between the emotional state of the animal and its ability to learn and remember. Studies into the neural mechanisms underlying these interactions have focused on stress-induced synaptic plasticity impairments in the hippocampus. However, other brain areas, including the amygdala and the prefrontal cortex (PFC), have been implicated in relation to stress-mediated effects on memory. ⋯ Finally, we examined the effects of an exposure to the elevated platform stress on the ability to induce LTP in this pathway. The results indicate that, at the same time when LTP is blocked in the hippocampus, it is also inhibited in the BLA-medial PFC pathway. These results call for a shift from a focused attention on the effects of stress on plasticity in the hippocampus to a system level approach that emphasizes the possible modification of interactions between relevant brain areas after an exposure to a stressful experience.