The Journal of neuroscience : the official journal of the Society for Neuroscience
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Resolution of inflammation is defective after spinal cord injury (SCI), which impairs tissue integrity and remodeling and leads to functional deficits. Effective pharmacological treatments for SCI are not currently available. Maresin 1 (MaR1) is a highly conserved specialized proresolving mediator (SPM) hosting potent anti-inflammatory and proresolving properties with potent tissue regenerative actions. ⋯ We report that inflammation after SCI is dysregulated in part due to inappropriate synthesis of proresolving lipid mediators. We demonstrate that the administration of the resolution agonist referred to as maresin 1 (MaR1) after SCI actively propagates resolution processes at the lesion site and improves neurological outcome. MaR1 is identified as an interventional candidate to attenuate dysregulated lesional inflammation and to restore functional recovery after SCI.
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Learning to read causes the development of a letter- and word-selective region known as the visual word form area (VWFA) within the human ventral visual object stream. Why does a reading-selective region develop at this anatomical location? According to one hypothesis, the VWFA develops at the nexus of visual inputs from retinotopic cortices and linguistic input from the frontotemporal language network because reading involves extracting linguistic information from visual symbols. Surprisingly, the anatomical location of the VWFA is also active when blind individuals read Braille by touch, suggesting that vision is not required for the development of the VWFA. ⋯ Why does this particular brain region become specialized for reading? We tested the hypothesis that the VWFA develops within the ventral visual stream because reading involves extracting linguistic information from visual symbols. Consistent with this hypothesis, we find that in congenitally blind Braille readers, but not sighted readers of print, the VWFA region is active during grammatical processing of spoken sentences. These results suggest that visual experience contributes to VWFA specialization, and that different neural implementations of reading are possible.
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Learning the associations between words and meanings is a fundamental human ability. Although the language network is cortically well defined, the role of the white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual and cross-situational word learning, we tested whether learning the meaning of a new word is related to the integrity of the language-related white matter pathways in 40 adults (18 women). ⋯ The left uncinate was predictive of cross-situational word learning. No significant correlations were found for the arcuate or the inferior-fronto-occipital fasciculus. While previous results showed that learning new phonological word forms is supported by the arcuate fasciculus, these findings demonstrate that learning new word-to-meaning associations is mainly dependent on temporal white matter pathways.
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We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous μ-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle: minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and κ-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated metabotropic glutamate receptor 1 (mGluR1) signaling, are critical to the transition from an EM2 nonresponsive state (during diestrus) to an analgesically responsive state (during proestrus). ⋯ We find that the magnitude of spinal endomorphin 2 (EM2) antinociception not only varies with stage of reproductive cycle, but is also differentially regulated during diestrus and proestrus. This finding highlights the need for sex-specific and cycle-specific approaches to pain management. Additionally, our finding that spinal EM2 antinociception in female rats is regulated by both the ebb and flow of spinal dynorphin/κ-opioid receptor signaling over the estrous cycle, as well as the nature of the endogenous mGluR1 activator, could encourage noncanonical pharmacological approaches to pain management, such as harnessing endogenous opioids for pain relief.
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This study aims to understand how functional connectivity (FC) between areas 3b and S2 alters following input deprivation and the neuronal basis of disrupted FC of resting-state fMRI signals. We combined submillimeter fMRI with microelectrode recordings to localize the deafferented digit regions in areas 3b and S2 by mapping tactile stimulus-evoked fMRI activations before and after cervical dorsal column lesion in each male monkey. An average afferent disruption of 97% significantly reduced fMRI, local field potential (LFP), and spike responses to stimuli in both areas. ⋯ These findings have important implications for fMRI studies aiming to probe FC alterations in pathological conditions involving deafferentation in humans. SIGNIFICANCE STATEMENT By directly comparing fMRI, local field potential, and spike signals in both tactile stimulation and resting states before and after severe disruption of dorsal column afferent, we demonstrated that reduction in fMRI responses to stimuli is accompanied by weakened resting-state fMRI functional connectivity (FC) in input-deprived and reorganized digit regions in area 3b of the S1 and S2. Concurrent reductions in local field potential and spike FC validated the use of resting-state fMRI signals for probing neural intrinsic FC alterations in pathological deafferented cortex, and indicated that disrupted FC between mesoscale functionally highly related regions may contribute to the behavioral impairments.