Neuroscience
-
Complete spinal transection in adult rats results in poor recovery of hind limb function, whereas significant spontaneous recovery can occur following spinal cord transection in rat neonates. The mechanisms underlying the recovery, however, are poorly understood. Recent studies in rodents suggested that the recovery is not due to axonal regeneration, but rather due to reorganization of the neural circuits in the spinal cord below the injury site, including central pattern generators. ⋯ BDA-positive axons in the rat spinal cord following neonatal spinal transection (neo ST) were longer than those in sham-operated or normal rats. The number of terminal buttons was also higher in spinal cords of neo ST rats compared with sham-operated or normal rats. These findings suggest that sensory fibers project more strongly and make more synapses following neo ST to compensate for the lack of supraspinal projections.
-
N-methyl-d-aspartate receptors (NMDARs) have been known to be regulated by various receptor tyrosine kinases. Activation of epidermal growth factor receptor (EGFR) specifically increases NMDAR-mediated currents and enhances long-term potentiation (LTP) in the hippocampus. However, the mechanism through which EGFR regulates NMDARs remains to be elucidated. ⋯ EGFR blockade with a specific antagonist BIBX-1382 attenuated an increase of GluN2B in the postsynaptic density during high-frequency stimulation (HFS)-induced LTP. Moreover, BIBX blockade significantly impaired HFS-induced LTP. In conclusion, our findings suggest that EGFR signaling upregulates NMDARs through modification of the GluN2B subunit, and is required for HFS-induced LTP in the hippocampus.
-
Recently, ribbon synapses to the hair cells (HCs) in the cochlea have become a novel site of interest in the investigation of noise-induced cochlear lesions in adult rodents (Kujawa and Liberman, 2009; Lin et al., 2011; Liu et al., 2012; Shi et al., 2013). Permanent noise-induced damage to this type of synapse can result in subsequent degeneration of spiral ganglion neurons (SGNs) in the absence of permanent changes to hearing sensitivity. To verify whether noise exposure during an early developmental period produces a similar impact on ribbon synapses, the present study examined the damaging effects of noise exposure in neonatal Kunming mice. ⋯ There were no significant differences in the hearing threshold between noise-exposed and control animals, which suggests that noise did not cause permanent loss of hearing sensitivity. However, noise exposure did produce a significant loss of ribbon synapses, particularly in P14d mice, which continued to increase from P4w to P8w. Additionally, a corresponding reduction in the amplitude of compound action potential (CAP) was observed in the noise-exposed groups at P4w and P8w, and the CAP latency was elongated, indicating a change in synaptic function.
-
Pain anticipation plays a critical role in pain chronification and results in disability due to pain avoidance. It is important to understand how different sensory modalities (auditory, visual or tactile) may influence pain anticipation as different strategies could be applied to mitigate anticipatory phenomena and chronification. In this study, using a countdown paradigm, we evaluated with magnetoencephalography the neural networks associated with pain anticipation elicited by different sensory modalities in normal volunteers. ⋯ Dorsolateral prefrontal cortex and mid-cingulate cortex showed significant activity during pain anticipation regardless of modality. Our results show pain anticipation is processed with great time efficiency by a highly specialized and hierarchical network. The highest degree of higher-order processing is modulated by context (pain) rather than content (modality) and rests within the associative limbic regions, corroborating their intrinsic role in chronification.
-
Comparative Study
Differential cerebellar GABAA receptor expression in mice with mutations in CaV2.1 (P/Q-type) calcium channels.
Ataxia is the predominant clinical manifestation of cerebellar dysfunction. Mutations in the human CACNA1A gene, encoding the pore-forming α1 subunit of CaV2.1 (P/Q-type) calcium channels, underlie several neurological disorders, including Episodic Ataxia type 2 and Familial Hemiplegic Migraine type 1 (FHM1). Several mouse mutants exist that harbor mutations in the orthologous Cacna1a gene. ⋯ We did not identify differences in the expression of GABAA receptor subunits or in the number of functional GABAA receptors in the non-ataxic R192Q KI strain. In contrast, tg(rol) mice had a ∼15% decrease in the number of functional GABAA receptors, whereas S218L KI mice showed a ∼29% increase. Our data suggest that differential changes in cerebellar GABAA receptor expression profile may contribute to the neurological phenotype of cerebellar ataxia and that targeting GABAA receptors might represent a feasible complementary strategy to treat cerebellar ataxia.