Nature neuroscience
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Nature neuroscience · Aug 2012
Comparative StudyCorticostriatal functional connectivity predicts transition to chronic back pain.
The mechanism of brain reorganization in pain chronification is unknown. In a longitudinal brain imaging study, subacute back pain (SBP) patients were followed over the course of 1 year. When pain persisted (SBPp, in contrast to recovering SBP and healthy controls), brain gray matter density decreased. Initially greater functional connectivity of nucleus accumbens with prefrontal cortex predicted pain persistence, implying that corticostriatal circuitry is causally involved in the transition from acute to chronic pain.
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Neuropathic pain, the most debilitating of all clinical pain syndromes, may be a consequence of trauma, infection or pathology from diseases that affect peripheral nerves. Here we provide a framework for understanding the spinal mechanisms of neuropathic pain as distinct from those of acute pain or inflammatory pain. ⋯ Stimulating P2X4 receptors initiates a core pain signaling pathway mediated by release of brain-derived neurotrophic factor, which produces a disinhibitory increase in intracellular chloride in nociceptive (pain-transmitting) neurons in the spinal dorsal horn. The changes caused by signaling from P2X4R(+) microglia to nociceptive transmission neurons may account for the main symptoms of neuropathic pain in humans, and they point to specific interventions to alleviate this debilitating condition.
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The primary visual cortex (V1) receives its driving input from the eyes via the lateral geniculate nucleus (LGN) of the thalamus. The lateral pulvinar nucleus of the thalamus also projects to V1, but this input is not well understood. We manipulated lateral pulvinar neural activity in prosimian primates and assessed the effect on supra-granular layers of V1 that project to higher visual cortex. ⋯ LGN responses were unaffected by these lateral pulvinar manipulations. Excitation of lateral pulvinar after LGN lesion activated supra-granular layer V1 neurons. Thus, lateral pulvinar is able to powerfully control and gate information outflow from V1.
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In the adult mammalian CNS, chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs) stabilize neuronal structure and restrict compensatory sprouting following injury. The Nogo receptor family members NgR1 and NgR2 bind to MAIs and have been implicated in neuronal inhibition. We found that NgR1 and NgR3 bind with high affinity to the glycosaminoglycan moiety of proteoglycans and participate in CSPG inhibition in cultured neurons. ⋯ The combined loss of Ngr1 and Ngr3 (Ngr1(-/-); Ngr3(-/-)), but not Ngr1 and Ngr2 (Ngr1(-/-); Ngr2(-/-)), was sufficient to mimic the triple mutant regeneration phenotype. Regeneration in Ngr1(-/-); Ngr3(-/-) mice was further enhanced by simultaneous ablation of Rptpσ (also known as Ptprs), a known CSPG receptor. Collectively, our results identify NgR1 and NgR3 as CSPG receptors, suggest that there is functional redundancy among CSPG receptors, and provide evidence for shared mechanisms of MAI and CSPG inhibition.
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Nature neuroscience · Feb 2012
Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons.
Epilepsy is a common and refractory neurological disorder, but the neuronal regulatory mechanisms of epileptogenesis remain largely unclear. Activity-dependent transcription of genes for neurotrophins such as brain-derived neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however, little is known about factors that may act as intrinsic, homeostatic or counterbalancing mechanisms. ⋯ In contrast, depleting ErbB4 in CaMKIIα-positive pyramidal neurons had no effect. Thus, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.