299 research outputs found

    ๋ง๊ฐ„์กฐ์˜์ฆ๊ฐ• ์ž๊ธฐ๊ณต๋ช…์˜์ƒ์„ ์ด์šฉํ•œ ์ผ์ธก์„ฑ ๋‚œ์ฒญ์—์„œ์˜ ์‹ ๊ฒฝ๊ฐ€์†Œ์„ฑ๋ณ€ํ™” ๊ด€์ฐฐ

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    ํ•™์œ„๋…ผ๋ฌธ(๋ฐ•์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์˜๊ณผ๋Œ€ํ•™ ์˜ํ•™๊ณผ,2019. 8. ์˜ค์Šนํ•˜.์„œ๋ก : ์ผ์ธก์„ฑ ๋‚œ์ฒญ์€ ๋‚œ์ฒญ์˜ ์‹œ๊ธฐ์— ๋”ฐ๋ฅธ ์ค‘์ถ” ์‹ ๊ฒฝ๊ณ„ ๊ฐ€์†Œ์„ฑ ๋ณ€ํ™”๋ฅผ ๊ฐ€์ ธ์˜จ๋‹ค. ํ•˜์ง€๋งŒ ์ž์„ธํ•œ ๋Œ€๋‡Œํ”ผ์งˆ ๋ฐ ํ”ผ์งˆ ํ•˜ ์‹ ๊ฒฝ๊ณ„ ๊ฐ€์†Œ์„ฑ ๋ณ€ํ™”๋Š” ์•Œ๋ ค์ง„ ๋ฐ” ์—†๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€ ์ผ์ธก์„ฑ ๋‚œ์ฒญ ์„ฑ์ธ ๋งˆ์šฐ์Šค ๋ชจ๋ธ์—์„œ ๋‚œ์ฒญ ์‹œ๊ธฐ์— ๋”ฐ๋ฅธ ์ค‘์ถ”์‹ ๊ฒฝ๊ณ„ ๊ฐ€์†Œ์„ฑ ๋ณ€ํ™”๋ฅผ ๋น„๊ตํ•˜๋Š” ๊ฒƒ์ด๋‹ค. ๋ฐฉ๋ฒ•: ์ƒํ›„ 8์ฃผ๋ น B57BL/6 ๋งˆ์šฐ์Šค๋ฅผ ์„ธ ๊ตฐ์œผ๋กœ ๋ถ„๋ฅ˜ํ•˜์˜€๋‹ค: ์ผ์ธก์„ฑ ๋‚œ์ฒญ 4์ฃผ๊ตฐ (11๋งˆ๋ฆฌ), ์ผ์ธก์„ฑ ๋‚œ์ฒญ 8์ฃผ๊ตฐ (11๋งˆ๋ฆฌ), ๊ทธ๋ฆฌ๊ณ  ์ •์ƒ ์ฒญ๋ ฅ๊ตฐ (9๋งˆ๋ฆฌ). ์ผ์ธก์„ฑ ๋‚œ์ฒญ๊ตฐ๋“ค์€ ์ขŒ์ธก ๋‹ฌํŒฝ์ด๊ด€์„ ํŒŒ๊ดด์‹œ์ผฐ๋‹ค. ๋ง๊ฐ„์กฐ์˜์ฆ๊ฐ• MRI ์‹œํ–‰ ์ „ 24์‹œ๊ฐ„๋™์•ˆ ๋ฐฑ์ƒ‰์†Œ์Œ์„ ์ฃผ์—ˆ๋‹ค. T1-weighted MRI ์˜์ƒ์—์„œ cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus (LL), inferior colliculus (IC), medial geniculate body (MG), ๊ทธ๋ฆฌ๊ณ  auditory cortex (AC) ๋ฅผ ๋ถ„์„ํ•˜์˜€๋‹ค. ๊ฐ ๊ทธ๋ฃน ๊ฐ„์— Mn2+-enhanced signal intensities (Mn2+SI)๋ฅผ ๋น„๊ต ํ•˜์˜€๋‹ค. ๊ฒฐ๊ณผ: ์ผ์ธก์„ฑ ๋‚œ์ฒญ 4์ฃผ๊ตฐ์—์„œ CN ์—์„œ ๋‚œ์ฒญ ์ธก์ด ๊ฑด ์ธก์— ๋น„ํ•˜์—ฌ ๋‚ฎ์€ Mn2+SI๋ฅผ ๋ณด์˜€๋‹ค. ๋ฐ˜๋ฉด์—, SOC, LL, ๊ทธ๋ฆฌ๊ณ  IC์—์„œ ๊ฑด ์ธก์ด ๋‚œ์ฒญ ์ธก์— ๋น„ํ•˜์—ฌ ๋‚ฎ์€ Mn2+SI๋ฅผ ๋ณด์˜€๋‹ค. ์ด์™€ ๊ฐ™์ด ๊ฐ์†Œํ•œ Mn2+SI๋Š” ์ผ์ธก์„ฑ ๋‚œ์ฒญ 8์ฃผ๊ตฐ์—์„œ ํšŒ๋ณต๋˜๋Š” ์–‘์ƒ์„ ๋ณด์˜€๋‹ค. ์–‘์ธก๊ฐ„ Mn2+SI ์ฐจ์ด๋Š” CN์—์„œ ๊ฐ€์žฅ ๋†’๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๊ณ , ์ƒ์œ„ ์ฒญ์‹ ๊ฒฝ๊ณ„๋กœ ๊ฐˆ์ˆ˜๋ก ์–‘์ธก๊ฐ„ Mn2+SI ์ฐจ์ด๊ฐ€ ์ž‘์•„์ง€๋Š” ์–‘์ƒ์„ ๋ณด์˜€๋‹ค. ๊ฒฐ๋ก : ์ผ์ธก์„ฑ ๋‚œ์ฒญ ์ดํ›„ ํ”ผ์งˆ ํ•˜ ์ฒญ์‹ ๊ฒฝ๊ณ„์˜ ํ™œ์„ฑ์€ ๊ฐ์†Œ๋œ๋‹ค. ๋˜ํ•œ ์–‘ ๊ท€๊ฐ„ ์ฒญ์‹ ๊ฒฝ๊ณ„ ํ™œ์„ฑ ์ฐจ์ด๋Š” ์ƒ์œ„ ์ฒญ์‹ ๊ฒฝ๊ณ„๋กœ ๊ฐˆ์ˆ˜๋ก ํฌ์„๋˜์—ˆ๋‹ค. ์ด๋Ÿฌํ•œ ๋ณ€ํ™”๋“ค์€ ์‹œ๊ฐ„์ด ์ง€๋‚จ์— ๋”ฐ๋ผ์„œ ํšŒ๋ณต๋˜์—ˆ๋‹ค. ์ผ์ธก์„ฑ ๋‚œ์ฒญ ์ดํ›„ ๋‚˜ํƒ€๋‚˜๋Š” ์ด์™€ ๊ฐ™์€ ํ”ผ์งˆ ํ•˜ ์ฒญ์‹ ๊ฒฝ๊ณ„ ๋ณ€ํ™”๋Š” ์ผ์ธก์„ฑ ๋‚œ์ฒญ ํ™˜์ž๋“ค์—์„œ ์ด๋ช…๊ณผ ์ธ๊ณต์™€์šฐ ์˜ˆํ›„์— ์˜ํ–ฅ์„ ์ค„ ๊ฒƒ์œผ๋กœ ์˜ˆ์ธก๋œ๋‹ค.Introduction: Single-sided deafness (SSD) induces cortical neural plastic changes according to duration of deafness. However, it is still unclear how the auditory cortical changes accompany the subcortical neural changes. The present study aimed to find the neural plastic changes in the cortical and subcortical auditory system following adult-onset single-sided deafness (SSD) using Mn-enhanced magnetic resonance imaging (MEMRI). Material and methods: B57BL/6 mice (postnatal 8 weeks old) were divided into three groups: the SSD-4-week group (postnatal 12 weeks old, n = 11), the SSD-8-week group (postnatal 16 weeks old, n = 11), and a normal hearing control group (postnatal 8 weeks old, n = 9). The left cochlea was ablated in the SSD groups. White Gaussian noise was delivered for 24 h before MEMRI acquisition. T1-weighted MRI data were analyzed from the cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus (LL), inferior colliculus (IC), medial geniculate body (MG), and auditory cortex (AC). The differences in relative Mn2+-enhanced signal intensities (Mn2+SI) and laterality were analyzed between the groups. Results: Four weeks after the SSD procedure, the ipsilateral side of the SSD showed significantly lower Mn2+SI in the CN than the control group. On the other hand, the contralateral side of the SSD demonstrated significantly lower Mn2+SI in the SOC, LL, and IC. These decreased Mn2+SI values were partially recovered at 8 weeks after the SSD procedure. The interaural Mn2+SI differences representing the interaural dominance were highest in CN, then became less prominent higher in the auditory neural system. The SSD-8-week group still showed interaural differences in the CN, LL and IC. In contrast, the MG and AC did not show any significant intergroup or interaural differences in Mn2+SI. Conclusion: Subcortical auditory neural activities were decreased after SSD, and the interaural differences were diluted in the higher auditory nervous system. These findings were attenuated with time. Subcortical auditory neural changes after SSD may contribute to the change in tinnitus severity and the outcomes of cochlear implantation in SSD patients.์˜๋ฌธ์ดˆ๋ก ------------------------------------------------------------------------------------- i ๋ชฉ์ฐจ ------------------------------------------------------------------------------------------ iii List of tables --------------------------------------------------------------------------------- iv List of figures -------------------------------------------------------------------------------- v List of abbreviations and symbols ---------------------------------------------------------vi ์„œ๋ก  -------------------------------------------------------------------------------------------1 ์—ฐ๊ตฌ์žฌ๋ฃŒ ๋ฐ ๋ฐฉ๋ฒ• -------------------------------------------------------------------------4 ์—ฐ๊ตฌ๊ฒฐ๊ณผ -------------------------------------------------------------------------------------9 ๊ณ ์ฐฐ ------------------------------------------------------------------------------------------11 ๊ฒฐ๋ก  ------------------------------------------------------------------------------------------17 ์ฐธ๊ณ ๋ฌธํ—Œ ------------------------------------------------------------------------------------18 Tables ----------------------------------------------------------------------------------------26 Figures ---------------------------------------------------------------------------------------27 ๊ตญ๋ฌธ์ดˆ๋ก-------------------------------------------------------------------------------------37 โ€ƒ List of tables Table 1. The hearing thresholds of each group -------------------------------------26 โ€ƒ List of figures Figure 1. Schematic diagram of the present study. ------------------------------27โ€ƒ Figure 2. The relative Mn2+-enhanced signal intensities (Mn2+SI) changes in the CN, SOC, LL, and IC in each group. -------------------------------------------29 โ€ƒ Figure 3. A quantitative analysis of the relative Mn2+-enhanced signal intensity (Mn2+SI) of each group at the CN, SOC, LL, IC, MG, and AC. --31โ€ƒ Figure 4. The relative Mn2+-enhanced signal intensity (Mn2+SI) ratios and absolute differences on the ipsilateral side to contralateral side ears in the CN, SOC, LL, IC, MG, and AC in each group. -----------------------------------33 โ€ƒ Figure 5 A quantitative analysis of the relative Mn2+-enhanced signal intensity (Mn2+SI) of conductive hearing loss (CHL) group at the CN, SOC, LL, IC, MG, and AC. --------------------------------------------------------------------34 Figure 6 The relative Mn2+-enhanced signal intensity (Mn2+SI) ratios and absolute differences on the ipsilateral side to contralateral side ears in the CN, SOC, LL, IC, MG, and AC in conductive hearing loss (CHL) group -36Docto

    Evidence of Key Tinnitus-Related Brain Regions Documented by a Unique Combination of Manganese-Enhanced MRI and Acoustic Startle Reflex Testing

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    Animal models continue to improve our understanding of tinnitus pathogenesis and aid in development of new treatments. However, there are no diagnostic biomarkers for tinnitus-related pathophysiology for use in awake, freely moving animals. To address this disparity, two complementary methods were combined to examine reliable tinnitus models (rats repeatedly administered salicylate or exposed to a single noise event): inhibition of acoustic startle and manganese-enhanced MRI. Salicylate-induced tinnitus resulted in wide spread supernormal manganese uptake compared to noise-induced tinnitus. Neither model demonstrated significant differences in the auditory cortex. Only in the dorsal cortex of the inferior colliculus (DCIC) did both models exhibit supernormal uptake. Therefore, abnormal membrane depolarization in the DCIC appears to be important in tinnitus-mediated activity. Our results provide the foundation for future studies correlating the severity and longevity of tinnitus with hearing loss and neuronal activity in specific brain regions and tools for evaluating treatment efficacy across paradigms

    Brain Struct Funct

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    Loud noise frequently results in hyperacusis or hearing loss (i.e., increased or decreased sensitivity to sound). These conditions are often accompanied by tinnitus (ringing in the ears) and changes in spontaneous neuronal activity (SNA). The ability to differentiate the contributions of hyperacusis and hearing loss to neural correlates of tinnitus has yet to be achieved. Towards this purpose, we used a combination of behavior, electrophysiology, and imaging tools to investigate two models of noise-induced tinnitus (either with temporary hearing loss or with permanent hearing loss). Manganese (Mn|) uptake was used as a measure of calcium channel function and as an index of SNA. Manganese uptake was examined in vivo with manganese-enhanced magnetic resonance imaging (MEMRI) in key auditory brain regions implicated in tinnitus. Following acoustic trauma, MEMRI, the SNA index, showed evidence of spatially dependent rearrangement of Mn| uptake within specific brain nuclei (i.e., reorganization). Reorganization of Mn| uptake in the superior olivary complex and cochlear nucleus was dependent upon tinnitus status. However, reorganization of Mn| uptake in the inferior colliculus\ua0was dependent upon hearing sensitivity. Furthermore, following permanent hearing loss, reduced Mn| uptake was observed. Overall, by combining testing for hearing sensitivity, tinnitus, and SNA, our data move forward the possibility of discriminating the contributions of hyperacusis and hearing loss to tinnitus.R21 EY021619/EY/NEI NIH HHS/United StatesT42 OH008455/OH/NIOSH CDC HHS/United StatesT42 OH008455/National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention/I01 RX001095/RX/RRD VA/United Statesunrestricted grant/Research to Prevent Blindness/1I01RX001095-01U.S/U.S. Department of Veterans Affairs/EY021619/National Institutes of Health/2019-06-01T00:00:00Z29488007PMC6129978631

    Thalamocortical Inputs Show Post-Critical-Period Plasticity

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    SummaryExperience-dependent plasticity in the adult brain has clinical potential for functional rehabilitation following central and peripheral nerve injuries. Here, plasticity induced by unilateral infraorbital (IO) nerve resection in 4-week-old rats was mapped using MRI and synaptic mechanisms were elucidated by slice electrophysiology. Functional MRI demonstrates a cortical potentiation compared to thalamus 2ย weeks after IO nerve resection. Tracing thalamocortical (TC) projections with manganese-enhanced MRI revealed circuit changes in the spared layer 4 (L4) barrel cortex. Brain slice electrophysiology revealed TC input strengthening onto L4 stellate cells due to an increase in postsynaptic strength and the number of functional synapses. This work shows that the TC input is a site for robust plasticity after the end of the previously defined critical period for this input. Thus, TC inputs may represent a major site for adult plasticity in contrast to the consensus that adult plasticity mainly occurs at cortico-cortical connections

    The Reorganization of Primary Auditory Cortex by Invasion of Ectopic Visual Inputs

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    Brain injury is a serious clinical problem. The success of recovery from brain injury involves functional compensation in the affected brain area. We are interested in general mechanisms that underlie compensatory plasticity after brain damage, particularly when multiple brain areas or multiple modalities are included. In this thesis, I studied the function of auditory cortex after recovery from neonatal midbrain damage as a model system that resembles patients with brain damage or sensory dysfunction. I addressed maladaptive changes of auditory cortex after invasion by ectopic visual inputs. I found that auditory cortex contained auditory, visual, and multisensory neurons after it recovered from neonatal midbrain damage (Mao et al. 2011). The distribution of these different neuronal responses did not show any clustering or segregation. As might be predicted from the fact that auditory neurons and visual neurons were intermingled throughout the entire auditory cortex, I found that residual auditory tuning and tonotopy in the rewired auditory cortex were compromised. Auditory tuning curves were broader and tonotopic maps were disrupted in the experimental animals. Because lateral inhibition is proposed to contribute to refinement of sensory maps and tuning of receptive fields, I tested whether loss of inhibition is responsible for the compromised auditory function in my experimental animals. I found an increase rather than a decrease of inhibition in the rewired auditory cortex, suggesting that broader tuning curves in the experimental animals are not caused by loss of lateral inhibition. These results suggest that compensatory plasticity can be maladaptive and thus impair the recovery of the original sensory cortical function. The reorganization of brain areas after recovery from brain damage may require stronger inhibition in order to process multiple sensory modalities simultaneously. These findings provide insight into compensatory plasticity after sensory dysfunction and brain damage and new information about the role of inhibition in cross-modal plasticity. This study can guide further research on design of therapeutic strategies to encourage adaptive changes and discourage maladaptive changes after brain damage, sensory/motor dysfunction, and deafferentation

    Noninvasive fMRI investigation of interaural level difference processing the rat auditory subcortex

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    Response of the primary auditory and non-auditory cortices to acoustic stimulation: A manganese-enhanced MRI study

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    Structural and functional features of various cerebral cortices have been extensively explored in neuroscience research. We used manganese-enhanced MRI, a non-invasive method for examining stimulus-dependent activity in the whole brain, to investigate the activity in the layers of primary cortices and sensory, such as auditory and olfactory, pathways under acoustic stimulation. Male Sprague-Dawley rats, either with or without exposure to auditory stimulation, were scanned before and 24-29 hour after systemic MnCl2 injection. Cortex linearization and layer-dependent signal extraction were subsequently performed for detecting layer-specific cortical activity. We found stimulus-dependent activity in the deep layers of the primary auditory cortex and the auditory pathways. The primary sensory and visual cortices also showed the enhanced activity, whereas the olfactory pathways did not. Further, we performed correlation analysis of the signal intensity ratios among different layers of each cortex, and compared the strength of correlations between with and without the auditory stimulation. In the primary auditory cortex, the correlation strength between left and right hemisphere showed a slight but not significant increase with the acoustic simulation, whereas, in the primary sensory and visual cortex, the correlation coefficients were significantly smaller. These results suggest the possibility that even though the primary auditory, sensory, and visual cortices showed enhanced activity to the auditory stimulation, these cortices had different associations for auditory processing in the brain network.open0

    Dissecting the neuronal basis of threat responding in mice

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    Environmental threats demand adaptive defensive responses of an organism that ensure its survival. Extreme stressors, however, can unbalance stress homeostasis and lead to long-term changes that impair appropriate defensive behaviors and emotional responses. In my thesis, I assessed (1) the interaction of two stress-related neuromodulatory systems, (2) the effects of a traumatic incident on brain volume and hyperarousal, and (3) sonic vocalization as a defensive behavior in mice, and discussed the topics in three independent studies.In the first study, I evaluated the interaction of two regulatory systems with respect to fear, anxiety, and trauma-related behaviors. Although the endocannabinoid and the corticotropin-releasing factor (CRF) systems are well described in modulating stressrelatedresponses, the direct interaction of both systems remained poorly understood. The generation of a new conditional knockout mouse line that selectively lacked the expression of the cannabinoid type 1 (CB1) receptor in CRF-positive neurons presented no differences in various tests of fear and anxiety-related behaviors under basal conditions or after a traumatic event. Also stress hormone levels were unaffected. However, male knockout animals exhibited a significantly increased acoustic startle response thus suggesting a specific involvement of CB1-CRF interactions in controlling arousal.In the second study, I assessed the consequences of a traumatic experience on behavior and grey matter volume in mice. Whole-brain deformation-based morphometry (DBM) by means of magnetic resonance imaging (MRI) after incubation of a traumatic incident showed changes in the dorsal hippocampus and the reticular nucleus. Using the severity of hyperarousal as regressor for cross-sectional volumetric differences between traumatized mice and controls revealed a negative correlation with the dorsal hippocampus. Further, longitudinal analysis including volumetric measurements before and after the traumatic incident showed that volume reductions in the globus pallidus reflect trauma-related changes in hyperarousal severity.In the third study, I characterized sonic vocalization as a defensive behavior in mice. Mice bred for high anxiety-related behavior (HAB) were found to have a high disposition to emit audible squeaks when taken by the tail which was not the case for any of the other five mouse lines tested. The calls emitted had a fundamental frequency of 3.8 kHz and were shown to be sensitive to anxiolytic but not panicolytic compounds. Manganese-enhanced MRI (MEMRI) scans pointed towards an increased tonic activity, among others, in the periaqueductal grey (PAG). Inhibition of the dorsal PAG by muscimol not only completely abolished sonic vocalization, but also reduced anxiety-like behavior. This suggests that sonic vocalization of mice is related to anxiety and controlled by the PAG. To explore the ecological relevance of defensive vocalization, I performed playback experiments with conspecifics and putative predators. Squeaks turned out to be aversive to HAB mice but became appetitive to both mice and rats when a stimulus mouse was present during playback.Collectively, the results of this thesis provide novel insights into fear and anxiety-related behaviors and shine light onto their mechanistic basis and ecological relevance
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