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- 발행기관 : Society for Neuroscience (검색결과 106 건)
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Pleiotropic Mitochondria: The Influence of Mitochondria on Neuronal Development and Disease
Rangaraju, Vidhya,Lewis Jr, Tommy L.,Hirabayashi, Yusuke,Bergami, Matteo,Motori, Elisa,Cartoni, Romain,Kwon, Seok-Kyu,Courchet, Julien Society for Neuroscience 2019 The Journal of neuroscience Vol.39 No.42
<P>Mitochondria play many important biological roles, including ATP production, lipid biogenesis, ROS regulation, and calcium clearance. In neurons, the mitochondrion is an essential organelle for metabolism and calcium homeostasis. Moreover, mitochondria are extremely dynamic and able to divide, fuse, and move along microtubule tracks to ensure their distribution to the neuronal periphery. Mitochondrial dysfunction and altered mitochondrial dynamics are observed in a wide range of conditions, from impaired neuronal development to various neurodegenerative diseases. Novel imaging techniques and genetic tools provide unprecedented access to the physiological roles of mitochondria by visualizing mitochondrial trafficking, morphological dynamics, ATP generation, and ultrastructure. Recent studies using these new techniques have unveiled the influence of mitochondria on axon branching, synaptic function, calcium regulation with the ER, glial cell function, neurogenesis, and neuronal repair. This review provides an overview of the crucial roles played by mitochondria in the CNS in physiological and pathophysiological conditions.</P>
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Kwon, Min Jung,Shin, Hae Young,Cui, Yuexian,Kim, Hyosil,Thi, Anh Hong Le,Choi, Jun Young,Kim, Eun Young,Hwang, Dong Hoon,Kim, Byung Gon Society for Neuroscience 2015 The Journal of neuroscience Vol.35 No.48
<P>CNS neurons in adult mammals do not spontaneously regenerate axons after spinal cord injury. Preconditioning peripheral nerve injury allows the dorsal root ganglia (DRG) sensory axons to regenerate beyond the injury site by promoting expression of regeneration-associated genes. We have previously shown that peripheral nerve injury increases the number of macrophages in the DRGs and that the activated macrophages are critical to the enhancement of intrinsic regeneration capacity. The present study identifies a novel chemokine signal mediated by CCL2 that links regenerating neurons with proregenerative macrophage activation. Neutralization of CCL2 abolished the neurite outgrowth activity of conditioned medium obtained from neuron-macrophage cocultures treated with cAMP. The neuron-macrophage interactions that produced outgrowth-promoting conditioned medium required CCL2 in neurons and CCR2/CCR4 in macrophages. The conditioning effects were abolished in CCL2-deficient mice at 3 and 7 d after sciatic nerve injury, but CCL2 was dispensable for the initial growth response and upregulation of GAP-43 at the 1 d time point. Intraganglionic injection of CCL2 mimicked conditioning injury by mobilizing M2-like macrophages. Finally, overexpression of CCL2 in DRGs promoted sensory axon regeneration in a rat spinal cord injury model without harmful side effects. Our data suggest that CCL2-mediated neuron-macrophage interaction plays a critical role for amplification and maintenance of enhanced regenerative capacity by preconditioning peripheral nerve injury. Manipulation of chemokine signaling mediating neuron-macrophage interactions may represent a novel therapeutic approach to promote axon regeneration after CNS injury.</P>
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Lee, Jungah,Kim, Kayeon,Chung, Sooyoung,Lee, Choongkil Society for Neuroscience 2013 The Journal of neuroscience Vol.33 No.9
<P>Visually guided saccadic eye movements are thought to involve multiple stages of processing in diverse brain structures including the primary visual cortex (V1). The variability of neural activity in each of these structures may present ambiguities for downstream stages in identifying sensory and motor signals among spontaneous discharges. The response time of saccadic eye movements made toward a visual target is correlated with the time of the first spikes in V1 that are evoked by the target (Lee et al., 2010). This suggests that downstream neurons receiving the output of V1 are faced with a challenging task of discriminating first spikes of visual response against spontaneous discharge. Here we report a novel response property of the macaque V1 neurons. Immediately before neurons discharge a burst of activity to a visual saccade target, spontaneous discharges were transiently suppressed. This suppression was maximal ∼18 ms after target onset. Based on simulations of artificial spike trains, we propose that the transient suppression enhances temporal contrast for identifying the onset of visual response by increasing the reliability of detection of response onset by downstream neurons, thereby facilitating visually guided behavioral responses.</P>
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Li, Gang,Wang, Li,Shi, Feng,Lyall, Amanda E.,Lin, Weili,Gilmore, John H.,Shen, Dinggang Society for Neuroscience 2014 The Journal of neuroscience Vol.34 No.12
<P>Human cortical folding is believed to correlate with cognitive functions. This likely correlation may have something to do with why abnormalities of cortical folding have been found in many neurodevelopmental disorders. However, little is known about how cortical gyrification, the cortical folding process, develops in the first 2 years of life, a period of dynamic and regionally heterogeneous cortex growth. In this article, we show how we developed a novel infant-specific method for mapping longitudinal development of local cortical gyrification in infants. By using this method, via 219 longitudinal 3T magnetic resonance imaging scans from 73 healthy infants, we systemically and quantitatively characterized for the first time the longitudinal cortical global gyrification index (GI) and local GI (LGI) development in the first 2 years of life. We found that the cortical GI had age-related and marked development, with 16.1% increase in the first year and 6.6% increase in the second year. We also found marked and regionally heterogeneous cortical LGI development in the first 2 years of life, with the high-growth regions located in the association cortex, whereas the low-growth regions located in sensorimotor, auditory, and visual cortices. Meanwhile, we also showed that LGI growth in most cortical regions was positively correlated with the brain volume growth, which is particularly significant in the prefrontal cortex in the first year. In addition, we observed gender differences in both cortical GIs and LGIs in the first 2 years, with the males having larger GIs than females at 2 years of age. This study provides valuable information on normal cortical folding development in infancy and early childhood.</P>
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Diversity and Homogeneity in Responses of Midbrain Dopamine Neurons
Fiorillo, Christopher D.,Yun, Sora R.,Song, Minryung R. Society for Neuroscience 2013 The Journal of neuroscience Vol.33 No.11
<P>Dopamine neurons of the ventral midbrain have been found to signal a reward prediction error that can mediate positive reinforcement. Despite the demonstration of modest diversity at the cellular and molecular levels, there has been little analysis of response diversity in behaving animals. Here we examine response diversity in rhesus macaques to appetitive, aversive, and neutral stimuli having relative motivational values that were measured and controlled through a choice task. First, consistent with previous studies, we observed a continuum of response variability and an apparent absence of distinct clusters in scatter plots, suggesting a lack of statistically discrete subpopulations of neurons. Second, we found that a group of “sensitive” neurons tend to be more strongly suppressed by a variety of stimuli and to be more strongly activated by juice. Third, neurons in the “ventral tier” of substantia nigra were found to have greater suppression, and a subset of these had higher baseline firing rates and late “rebound” activation after suppression. These neurons could belong to a previously identified subgroup of dopamine neurons that express high levels of H-type cation channels but lack calbindin. Fourth, neurons further rostral exhibited greater suppression. Fifth, although we observed weak activation of some neurons by aversive stimuli, this was not associated with their aversiveness. In conclusion, we find a diversity of response properties, distributed along a continuum, within what may be a single functional population of neurons signaling reward prediction error.</P>
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Choe, Youngshik,Huynh, Trung,Pleasure, Samuel J. Society for Neuroscience 2014 The Journal of neuroscience Vol.34 No.45
<P>During embryonic development oligodendrocyte precursor cells (OPCs) are generated first in the ventral forebrain and migrate dorsally to occupy the cortex. The molecular cues that guide this migratory route are currently completely unknown. Here, we show that bone morphogenetic protein-4 (Bmp4), Bmp7, and Tgfβ1 produced by the meninges and pericytes repelled ventral OPCs into the cortex at mouse embryonic stages. Ectopic activation of Bmp or Tgfβ1 signaling before the entrance of OPCs into the cortex hindered OPC migration into the cortical areas. OPCs without Smad4 signaling molecules also failed to migrate into the cortex efficiently and formed heterotopia in ventral areas. OPC migration into the cortex was also dramatically reduced by conditional inhibition of Tgfβ1 or Bmp expression from mesenchymal cells. The data suggest that mesenchymal Tgfβ family proteins promote migration of ventral OPCs into the cortex during corticogenesis.</P>
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Lee, Kyu-Hee,Lee, Hyunsu,Yang, Che Ho,Ko, Jeong-Soon,Park, Chang-Hwan,Woo, Ran-Sook,Kim, Joo Yeon,Sun, Woong,Kim, Joung-Hun,Ho, Won-Kyung,Lee, Suk-Ho Society for Neuroscience 2015 The Journal of neuroscience Vol.35 No.50
<P>Expression of neuregulin-2 (NRG2) is intense in a few regions of the adult brain where neurogenesis persists; however, little is understood about its role in developments of newborn neurons. To study the role of NRG2 in synaptogenesis at different developmental stages, newborn granule cells in rat hippocampal slice cultures were labeled with retrovirus encoding tetracycline-inducible microRNA targeting NRG2 and treated with doxycycline (Dox) at the fourth or seventh postinfection day (dpi). The developmental increase of GABAergic postsynaptic currents (GPSCs) was suppressed by the early Dox treatment (4 dpi), but not by late treatment (7 dpi). The late Dox treatment was used to study the effect of NRG2 depletion specific to excitatory synaptogenesis. The Dox effect on EPSCs emerged 4 d after the impairment in dendritic outgrowth became evident (10 dpi). Notably, Dox treatment abolished the developmental increases of AMPA-receptor mediated EPSCs and the AMPA/NMDA ratio, indicating impaired maturation of glutamatergic synapses. In contrast to GPSCs, Dox effects on EPSCs and dendritic growth were independent of ErbB4 and rescued by concurrent overexpression of NRG2 intracellular domain. These results suggest that forward signaling of NRG2 mediates GABAergic synaptogenesis and its reverse signaling contributes to dendritic outgrowth and maturation of glutamatergic synapses.</P><P><B>SIGNIFICANCE STATEMENT</B> The hippocampal dentate gyrus is one of special brain regions where neurogenesis persists throughout adulthood. Synaptogenesis is a critical step for newborn neurons to be integrated into preexisting neural network. Because neuregulin-2 (NRG2), a growth factor, is intensely expressed in these regions, we investigated whether it plays a role in synaptogenesis and dendritic growth. We found that NRG2 has dual roles in the development of newborn neurons. For GABAergic synaptogenesis, the extracellular domain of NRG2 acts as a ligand for a receptor on GABAergic neurons. In contrast, its intracellular domain was essential for dendritic outgrowth and glutamatergic synapse maturation. These results imply that NRG2 may play a critical role in network integration of newborn neurons.</P>
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Neural Correlates of Interval Timing in Rodent Prefrontal Cortex
Kim, Jieun,Ghim, Jeong-Wook,Lee, Ji Hyun,Jung, Min Whan Society for Neuroscience 2013 The Journal of neuroscience Vol.33 No.34
<P>Time interval estimation is involved in numerous behavioral processes, but its underlying neural mechanisms remain unclear. In particular, it has been controversial whether time is encoded on a linear or logarithmic scale. Based on our previous finding that inactivation of the medial prefrontal cortex (mPFC) profoundly impairs rat's ability to discriminate time intervals, we investigated how the mPFC processes temporal information by examining activity of mPFC neurons in rats performing a temporal bisection task. Many mPFC neurons conveyed temporal information based on monotonically changing activity profiles over time with negative accelerations, so that their activity profiles were better described by logarithmic than linear functions. Moreover, the precision of time-interval discrimination based on neural activity was lowered in proportion to the elapse of time, but without proportional increase in neural variability, which is well accounted for by logarithmic, but not by linear functions. As a population, mPFC neurons conveyed precise information about the elapse of time with their activity tightly correlated with the animal's choice of target. These results suggest that the mPFC might be part of an internal clock in charge of controlling interval-timing behavior, and that linearly changing neuronal activity on a logarithmic time scale might be one way of representing the elapse of time in the brain.</P>
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