The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Daniel A Llano - One of the best experts on this subject based on the ideXlab platform.
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ageing related changes in GABAergic inhibition in mouse auditory cortex measured using in vitro flavoprotein autofluorescence imaging
The Journal of Physiology, 2016Co-Authors: Kevin A Stebbings, H W Choi, A Ravindra, Donald M Caspary, Jeremy G Turner, Daniel A LlanoAbstract:Key points Ageing is associated with hearing loss and changes in GABAergic signalling in the auditory system. We tested whether GABAergic signalling in an isolated forebrain preparation also showed ageing-related changes. A novel approach was used, whereby population imaging was coupled to quantitative pharmacological sensitivity. Sensitivity to GABAA blockade was inversely associated with age and cortical thickness, but hearing loss did not independently contribute to the change in GABAAergic sensitivity. Redox states in the auditory cortex of young and aged animals were similar, suggesting that the differences in GABAAergic sensitivity are unlikely to be due to differences in slice health. Abstract To examine ageing-related changes in the earliest stages of auditory cortical processing, population auditory cortical responses to thalamic afferent stimulation were studied in brain slices obtained from young and aged CBA/CAj mice (up to 28 months of age). Cortical responses were measured using flavoprotein autofluorescence imaging, and ageing-related changes in inhibition were assessed by measuring the sensitivity of these responses to blockade of GABAA receptors using bath-applied SR95531. The maximum auditory cortical response to afferent stimulation was not different between young and aged animals under control conditions, but responses to afferent stimulation in aged animals showed a significantly lower sensitivity to GABA blockade with SR95531. Cortical thickness, but not hearing loss, improved the prediction of all imaging variables when combined with age, particularly sensitivity to GABA blockade for the maximum response. To determine if the observed differences between slices from young and aged animals were due to differences in slice health, the redox state in the auditory cortex was assessed by measuring the FAD+/NADH ratio using fluorescence imaging. We found that this ratio is highly sensitive to known redox stressors such as H2O2 and NaCN; however, no difference was found between young and aged animals. By using a new approach to quantitatively assess pharmacological sensitivity of population-level cortical responses to afferent stimulation, these data demonstrate that auditory cortical inhibition diminishes with ageing. Furthermore, these data establish a significant relationship between cortical thickness and GABAergic sensitivity, which had not previously been observed in an animal model of ageing.
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open loop organization of thalamic reticular nucleus and dorsal thalamus a computational model
Journal of Neurophysiology, 2015Co-Authors: Bernard J Slater, Adam M Willis, Ekaterina Gribkova, Daniel A LlanoAbstract:The thalamic reticular nucleus (TRN) is a shell of GABAergic neurons that surrounds the dorsal thalamus. Previous work has shown that TRN neurons send GABAergic projections to thalamocortical (TC) ...
Adam M Willis - One of the best experts on this subject based on the ideXlab platform.
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open loop organization of thalamic reticular nucleus and dorsal thalamus a computational model
Journal of Neurophysiology, 2015Co-Authors: Bernard J Slater, Adam M Willis, Ekaterina Gribkova, Daniel A LlanoAbstract:The thalamic reticular nucleus (TRN) is a shell of GABAergic neurons that surrounds the dorsal thalamus. Previous work has shown that TRN neurons send GABAergic projections to thalamocortical (TC) ...
Ilsung Jang - One of the best experts on this subject based on the ideXlab platform.
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α2a adrenoceptor mediated presynaptic inhibition of GABAergic transmission in rat tuberomammillary nucleus neurons
Journal of Neurochemistry, 2013Co-Authors: Michiko Nakamura, Ilsung JangAbstract:Histaminergic neurons within the tuberomammillary nucleus (TMN) play an important role in the regulation of sleep-wakefulness. Here, we report the adrenergic modulation of GABAergic transmission in rat TMN histaminergic neurons using a conventional whole-cell patch clamp technique. Norepinephrine (NE) reversibly decreased the amplitude of action potential-dependent GABAergic inhibitory post-synaptic currents (IPSCs) and increased the paired pulse ratio. The NE-induced inhibition of GABAergic IPSCs was mimicked by clonidine, a selective α2 adrenoceptor agonist. However, cirazoline and isoproterenol, nonselective α1 and β adrenoceptor agonists, respectively, had no effect on GABAergic IPSCs. The NE-induced inhibition of GABAergic IPSCs was significantly blocked by BRL44408, a selective α2A adrenoceptor antagonist, but not imiloxan or JP1302, a selective α2B and α2C adrenoceptor antagonists. The extent of NE-induced inhibition of GABAergic IPSCs was inversely proportional to the extracellular Ca2+ concentration. Pharmacological agents affecting the activities of adenylyl cyclase or G-protein-coupled inwardly rectifying K+ channels did not affect the NE-induced inhibition of GABAergic IPSCs. However, NE had no effect on the frequency and amplitude of GABAergic miniature IPSCs. These results suggest that NE acts on presynaptic α2A adrenoceptor to inhibit action potential-dependent GABA release via the inhibition of Ca2+ influx from the extracellular space to GABAergic nerve terminals, and that this α2A adrenoceptor-mediated modulation of GABAergic transmission may be involved in regulating the excitability of TMN histaminergic neurons.
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adenosine a1 receptors inhibit GABAergic transmission in rat tuberomammillary nucleus neurons
Journal of Neurochemistry, 2008Co-Authors: Insun Choi, Jaekap Choi, Michiko Nakamura, Byungju Choi, Ilsung JangAbstract:The adenosinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) was investigated in mechanically dissociated rat tuberomammillary nucleus (TMN) neurons using a conventional whole-cell patch clamp technique. Adenosine (100 μM) reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that adenosine acts presynaptically to decrease the probability of spontaneous GABA release. The adenosine action on GABAergic mIPSC frequency was completely blocked by 1 μM DPCPX, a selective A1 receptor antagonist, and mimicked by 1 μM CPA, a selective A1 receptor agonist. This suggests that presynaptic A1 receptors were responsible for the adenosine-mediated inhibition of GABAergic mIPSC frequency. CPA still decreased GABAergic mIPSC frequency even either in the presence of 200 μM Cd2+, a general voltage-dependent Ca2+ channel blocker, or in the Ca2+-free external solution. However, the inhibitory effect of CPA on GABAergic mIPSC frequency was completely occluded by 1 mM Ba2+, a G-protein coupled inwardly rectifying K+ (GIRK) channel blocker. In addition, the CPA-induced decrease in mIPSC frequency was completely occluded by either 100 μM SQ22536, an adenylyl cyclase (AC) inhibitor, or 1 μM KT5720, a specific protein kinase A (PKA) inhibitor. The results suggest that the activation of presynaptic A1 receptors decreases spontaneous GABAergic transmission onto TMN neurons via the modulation of GIRK channels as well as the AC/cAMP/PKA signal transduction pathway. This adenosine A1 receptor-mediated modulation of GABAergic transmission onto TMN neurons may play an important role in the fine modulation of the excitability of TMN histaminergic neurons as well as the regulation of sleep-wakefulness.
Yuchio Yanagawa - One of the best experts on this subject based on the ideXlab platform.
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Corticofugal GABAergic projection neurons in the mouse frontal cortex.
Frontiers in Neuroanatomy, 2015Co-Authors: Ryohei Tomioka, Kenji Sakimura, Yuchio YanagawaAbstract:Cortical projection neurons are classified by hodology in corticocortical, commissural and corticofugal subtypes. Although cortical projection neurons had been regarded as only glutamatergic neurons, recently corticocortical GABAergic projection neurons has been also reported in several species. Here, we demonstrate corticofugal GABAergic projection neurons in the mouse frontal cortex. We employed viral-vector-mediated anterograde tracing, classical retrograde tracing, and immunohistochemistry to characterize neocortical GABAergic projection neurons. Injections of the Cre-dependent adeno-associated virus into glutamate decarboxylase 67 (GAD67)-Cre knock-in mice revealed neocortical GABAergic projections widely to the forebrain, including the cerebral cortices, caudate putamen (CPu), ventral pallidum (VP), lateral globus pallidus (LGP), nucleus accumbens, and olfactory tubercle (Tu). Minor GABAergic projections were also found in the mediodorsal thalamic nucleus, diagonal band of Broca, medial globus pallidus, substantial nigra, and dorsal raphe nucleus. Retrograde tracing studies also demonstrated corticofugal GABAergic projection neurons in the mouse frontal cortex. Further immunohistochemical screening with neurochemical markers revealed the majority of corticostriatal GABAergic projection neurons were positive for somatostatin (SS)-immunoreactivity. In contrast, corticothalamic GABAergic projection neurons were not identified by representative neurochemical markers for GABAergic neurons. These findings suggest that corticofugal GABAergic projection neurons are heterogeneous in terms of their neurochemical properties and target nuclei, and provide axonal innervations mainly to the nuclei in the basal ganglia.
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neurochemical properties of the synapses between the parabrachial nucleus derived cgrp positive axonal terminals and the GABAergic neurons in the lateral capsular division of central nucleus of amygdala
Molecular Neurobiology, 2015Co-Authors: Yanzhou Chen, Yuchio Yanagawa, Yanyan Wei, Wen Wang, Yulin DongAbstract:The lateral capsular division of central nucleus of amygdala (CeC) contains neurons using γ-amino butyric acid (GABA) as the predominant neurotransmitter and expresses abundant calcitonin gene-related peptide (CGRP)-positive terminals. However, the relationship between them has not been revealed yet. Using GAD67-green fluorescent protein (GFP) knock-in mouse, we investigated the neurochemical features of synapses between CGRP-positive terminals and GABAergic neurons within CeC and the potential involvement of CGRP1 receptor by combining fluorescent in situ hybridization for CGRP1 receptor mRNA with immunofluorescent histochemistry for GFP and CGRP. The ultrastructures of these synapses were investigated with pre-embedding electron microscopy for GFP and CGRP. We found that some GABAergic neurons in the CeC received parabrachial nucleus (PBN) derived CGRP innervations and some of these GABAergic neurons can be activated by subcutaneous injection of formalin. Moreover, more than 90 % GABAergic neurons innervated by CGRP-positive terminal also express CGRP1 receptor mRNA. The CGRP-positive fibers made symmetric synapses onto the GABAergic somata, and asymmetric synapses onto the GABA-LI dendritic shafts and spines. This study provides direct ultrastructural evidences for the synaptic contacts between CGRP-positive terminals and GABAergic neurons within the CeC, which may underlie the pain-related neural pathway from PBN to CeC and be involved in the chronic pain modulation.
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laminar specific maturation of GABAergic transmission and susceptibility to visual deprivation are related to endocannabinoid sensitivity in mouse visual cortex
The Journal of Neuroscience, 2010Co-Authors: Bin Jiang, Kazuhiro Sohya, Abdolrahman Sarihi, Yuchio Yanagawa, Tadaharu TsumotoAbstract:The developmental period when neuronal responses are modified by visual experience is reported to start and end earlier in layer 4 than in layer 2/3 of the visual cortex, and the maturation of GABAergic inhibitory circuits is suggested to determine the timing of this period. Here, we examine whether the laminar difference in such timing corresponds to a difference in the time course of the functional maturation of GABAergic synaptic transmission to star pyramidal and pyramidal cells in layers 4 and 2/3, respectively, of the mouse visual cortex and whether the development of the strength of GABAergic transmission is affected by visual deprivation in a laminar-specific manner. Our analysis of developmental changes in inhibitory postsynaptic currents of star pyramidal and pyramidal cells evoked by electrical stimulation of afferents or action potentials of fast-spiking GABAergic neurons revealed that there was a sequential maturation of GABAergic function from layers 4 to 2/3. The maturation of inhibition in layer 4 occurred at postnatal week 3, which preceded by 1 week that of layer 2/3. Visual deprivation by dark rearing arrested the functional development of GABAergic transmission in layer 2/3, whereas dark rearing was not so effective in layer 4. GABAergic synapses in layer 2/3 were sensitive to an agonist for cannabinoid type 1 receptors and not normally matured in receptor knock-out mice, whereas those in layer 4 were not so. These results suggest laminar-specific maturation of inhibition and susceptibility to visual deprivation, which may be related to the laminar difference in sensitivity to endocannabinoids.
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Low accumulation of drebrin at glutamatergic postsynaptic sites on GABAergic neurons
Neuroscience, 2010Co-Authors: Kenji Hanamura, Yuchio Yanagawa, Hiroyuki Yamazaki, Toshikazu Kakizaki, Toshiyuki Mizui, Reiko T. Roppongi, Tomoaki ShiraoAbstract:Glutamatergic synapses form onto both glutamatergic and GABAergic neurons. These two types of glutamatergic synapses differ in their electrical responses to high-frequency stimulation and postsynaptic density protein composition. However, it is not known whether they differ in the actin cytoskeleton composition. In the present study, we used hippocampal neuronal cultures prepared from glutamate decarboxylase 67 (GAD67)-GFP knock-in mice and analyzed the differences in the actin cytoskeleton at glutamatergic synapses contacting GABAergic and glutamatergic neurons. Drebrin-binding actin filaments enriched in dendritic spines are known to play a pivotal role in spine formation. Immunocytochemical analyses demonstrated that drebrin accumulated at glutamatergic synapses on GABAergic neurons as well as at those on glutamatergic neurons. However, the density of drebrin clusters along dendrites in GABAergic neurons was significantly lower than those of glutamatergic neurons. Furthermore, the level of drebrin accumulating at glutamatergic synapses was lower on GABAergic neurons than on glutamatergic neurons. In neurons overexpressing drebrin, drebrin cluster density and accumulation levels in GABAergic and glutamatergic neurons were similar, suggesting that the low drebrin levels in the glutamatergic postsynaptic sites on GABAergic neurons may be because GABAergic neurons express low levels of drebrin. On the other hand, pharmacological analysis demonstrated that the postsynaptic localization of drebrin depended on actin cytoskeleton organization in both GABAergic and glutamatergic neurons. Together these results indicated that, although GABAergic and glutamatergic neurons share common regulatory systems affecting drebrin localization, the density of drebrin-positive glutamatergic synapses formed on GABAergic neurons is lower than those on glutamatergic neurons. This is probably due to the low expression of drebrin in GABAergic neurons.
Tadaharu Tsumoto - One of the best experts on this subject based on the ideXlab platform.
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laminar specific maturation of GABAergic transmission and susceptibility to visual deprivation are related to endocannabinoid sensitivity in mouse visual cortex
The Journal of Neuroscience, 2010Co-Authors: Bin Jiang, Kazuhiro Sohya, Abdolrahman Sarihi, Yuchio Yanagawa, Tadaharu TsumotoAbstract:The developmental period when neuronal responses are modified by visual experience is reported to start and end earlier in layer 4 than in layer 2/3 of the visual cortex, and the maturation of GABAergic inhibitory circuits is suggested to determine the timing of this period. Here, we examine whether the laminar difference in such timing corresponds to a difference in the time course of the functional maturation of GABAergic synaptic transmission to star pyramidal and pyramidal cells in layers 4 and 2/3, respectively, of the mouse visual cortex and whether the development of the strength of GABAergic transmission is affected by visual deprivation in a laminar-specific manner. Our analysis of developmental changes in inhibitory postsynaptic currents of star pyramidal and pyramidal cells evoked by electrical stimulation of afferents or action potentials of fast-spiking GABAergic neurons revealed that there was a sequential maturation of GABAergic function from layers 4 to 2/3. The maturation of inhibition in layer 4 occurred at postnatal week 3, which preceded by 1 week that of layer 2/3. Visual deprivation by dark rearing arrested the functional development of GABAergic transmission in layer 2/3, whereas dark rearing was not so effective in layer 4. GABAergic synapses in layer 2/3 were sensitive to an agonist for cannabinoid type 1 receptors and not normally matured in receptor knock-out mice, whereas those in layer 4 were not so. These results suggest laminar-specific maturation of inhibition and susceptibility to visual deprivation, which may be related to the laminar difference in sensitivity to endocannabinoids.
