1.Whole-Brain Connectome of GABAergic Neurons in the Mouse Zona Incerta.
Yang YANG ; Tao JIANG ; Xueyan JIA ; Jing YUAN ; Xiangning LI ; Hui GONG
Neuroscience Bulletin 2022;38(11):1315-1329
The zona incerta (ZI) is involved in various functions and may serve as an integrative node of the circuits for global behavioral modulation. However, the long-range connectivity of different sectors in the mouse ZI has not been comprehensively mapped. Here, we obtained whole-brain images of the input and output connections via fluorescence micro-optical sectioning tomography and viral tracing. The principal regions in the input-output circuits of ZI GABAergic neurons were topologically organized. The 3D distribution of cortical inputs showed rostro-caudal correspondence with different ZI sectors, while the projection fibers from ZI sectors were longitudinally organized in the superior colliculus. Clustering results show that the medial and lateral ZI are two different major functional compartments, and they can be further divided into more subdomains based on projection and input connectivity. This study provides a comprehensive anatomical foundation for understanding how the ZI is involved in integrating different information, conveying motivational states, and modulating global behaviors.
Animals
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Mice
;
Zona Incerta
;
GABAergic Neurons
;
Connectome
2.Interhemispheric Modulation on Afferent Sensory Transmission to the Ventral Posterior Medial Thalamus by Contralateral Primary Somatosensory Cortex.
Sung Cherl JUNG ; In Sun CHOI ; Jin Hwa CHO ; Ji Hyun KIM ; Yong Chul BAE ; Maan Gee LEE ; Hyung Cheul SHIN ; Byung Ju CHOI
The Korean Journal of Physiology and Pharmacology 2004;8(3):129-132
Single unit responses of the ventral posterior medial (VPM) thalamic neurons to stimulation were monitored in anesthetized rats during activation of contralateral primary somatosensory (SI) cortex by GABA antagonist. The temporal changes of afferent sensory transmission were quantitatively analyzed by poststimulus time histogram (PSTH). Mainly, afferent sensory transmission to VPM thalamus was facilitated (15 neurons of total 23) by GABA antagonist (bicuculline) applied to contralateral cortex, while 7 neurons were suppressed. However, when ipsilateral cortex was inactivated by GABA agonist, musimol, there was significant suppression of afferent sensory transmission of VPM thalamus. This suppressed responsiveness by ipsilateral musimol was not affected by bicuculline applied to contralateral cortex. These results suggest that afferent transmission to VPM thalamus may be subjected to the interhemispheric modulation via ipsilateral cortex during inactivation of GABAergic neurons in contralateral SI cortex.
Animals
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Bicuculline
;
GABA Agonists
;
GABA Antagonists
;
GABAergic Neurons
;
gamma-Aminobutyric Acid
;
Neurons
;
Rats
;
Somatosensory Cortex*
;
Thalamus*
3.O-GlcNAcylation in Ventral Tegmental Area Dopaminergic Neurons Regulates Motor Learning and the Response to Natural Reward.
Ming-Shuo SHAO ; Xiao YANG ; Chen-Chun ZHANG ; Chang-You JIANG ; Ying MAO ; Wen-Dong XU ; Lan MA ; Fei-Fei WANG
Neuroscience Bulletin 2022;38(3):263-274
Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.
Animals
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Dopaminergic Neurons/physiology*
;
GABAergic Neurons/physiology*
;
Mice
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Nucleus Accumbens/metabolism*
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Reward
;
Ventral Tegmental Area/metabolism*
4.Colocalization of GABA and Glycine within the Neurons of the Rat Retina.
Wook Hyun SON ; Soo Ja OH ; In Bum KIM ; Myung Hoon CHUN ; Jin Woong JUNG
Korean Journal of Anatomy 1997;30(6):695-704
The role of GABA or glycine as an inhibitory neurotransmitter is well established, and GABAergic or glycinergic neurons appear to play an important role in the mammalian retinas. It has been reported that certain amacrine, bipolar, displaced amacrine and ganglion cells are consistently labeled with anti-GABA or anti-glycine antisera in the mammalian retinae so far, and it has been suggested that colocalization of GABA and glycine within the retinal neurons could be common in the mammalian retina by recent immunecytochemical and electrophysiological studies. This study was conducted to localize GABAergic and glycinergic neurons and to define whether GABA and glycine are colocalized within same retinal neurons of the rat retina by immunocytochemical method using anti-GABA and anti-glycine antisera. The results were as follows : 1. GABAergic neurons of the rat retina were amacrine, interplexiform, bipolar, displaced amacrine and ganglion cells, and processes of GABAergic neurons formed dense networks with distinct two bands in the inner plexiform layer. 2. Glycinergic neurons were amacrine, bipolar, displaced amacrine and ganglion cells,and their processes were evenly distributed as dense networks through whole inner plexiform layer. 3. 28.5% of GABA immunoreactive amacrine cells and 9.8% of GABA immunoreactive bipolar cells located in the inner nuclear layer,and 11.9% of labeled neurons located in the ganglion cell layer showed glycine immunoreactivity in the rat retina. These results demonstrate that GABA and glycine, major inhibitory neurotransmitters, are colocalized within certain amacrine and displaced amacrine cells, and a few bipolar cells, and that neurons synthesizing and utilizing both GABA and glycine as their neurotransmitters may play an unique role in the visual processing in the rat retina.
Amacrine Cells
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Animals
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GABAergic Neurons
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gamma-Aminobutyric Acid*
;
Ganglion Cysts
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Glycine*
;
Immune Sera
;
Neurons*
;
Neurotransmitter Agents
;
Rats*
;
Retina*
;
Retinal Neurons
5.Revealing the Precise Role of Calretinin Neurons in Epilepsy: We Are on the Way.
Yingbei QI ; Heming CHENG ; Yi WANG ; Zhong CHEN
Neuroscience Bulletin 2022;38(2):209-222
Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain. Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons. Calretinin (CR) is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons. The functions of CR and its role in neural excitability are still unknown. Recent data suggest that CR neurons have diverse neurotransmitters, morphologies, distributions, and functions in different brain regions across various species. Notably, CR neurons in the hippocampus, amygdala, neocortex, and thalamus are extremely susceptible to excitotoxicity in the epileptic brain, but the causal relationship is unknown. In this review, we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy. Importantly, we provide perspectives on future investigations of the role of CR neurons in epilepsy.
Amygdala/metabolism*
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Calbindin 2/metabolism*
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Epilepsy
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GABAergic Neurons
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Hippocampus/metabolism*
;
Humans
6.Effects of post-traumatic stress disorder on the excitability of glutamatergic and GABAergic neurons in dorsal and ventral hippocampus in mice.
Dong-Bo LIU ; Yan SHI ; Shen-Ping ZHENG ; Hao-Ran ZHOU ; Li-Wei ZHAO
Acta Physiologica Sinica 2023;75(3):369-378
The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.
Mice
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Male
;
Animals
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Stress Disorders, Post-Traumatic
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Hippocampus
;
Spatial Learning
;
GABAergic Neurons
7.Activation of GABAergic neurons in the zona incerta accelerates anesthesia induction with sevoflurane and propofol without affecting anesthesia maintenance or awakening in mice.
Fuyang CAO ; Yongxin GUO ; Shuting GUO ; Zhikang ZHOU ; Jiangbei CAO ; Li TONG ; Weidong MI
Journal of Southern Medical University 2023;43(5):718-726
OBJECTIVE:
To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia.
METHODS:
Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons.
RESULTS:
In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P < 0.05), and also shorter in ChR2 group than in GFP group (P < 0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P < 0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance.
CONCLUSION
Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening.
Male
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Animals
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Mice
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Mice, Inbred C57BL
;
Propofol/pharmacology*
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Sevoflurane/pharmacology*
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Zona Incerta
;
Anesthesia, General
;
GABAergic Neurons
8.Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation.
Ming ZHANG ; Cong LI ; Qian XUE ; Chang-Bo LU ; Huan ZHAO ; Fan-Cheng MENG ; Ying ZHANG ; Sheng-Xi WU ; Yan ZHANG ; Hui XU
Neuroscience Bulletin 2023;39(9):1348-1362
The rostral agranular insular cortex (RAIC) has been associated with pain modulation. Although the endogenous cannabinoid system (eCB) has been shown to regulate chronic pain, the roles of eCBs in the RAIC remain elusive under the neuropathic pain state. Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve (CPN) ligation. The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice, glutamatergic, or GABAergic neuron cannabinoid receptor 1 (CB1R) knockdown mice with the whole-cell patch-clamp and pain behavioral methods. The E/I ratio (amplitude ratio between mEPSCs and mIPSCs) was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice. Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice. The analgesic effect of ACEA (a CB1R agonist) was alleviated along with bilateral dorsolateral funiculus lesions, with the administration of AM251 (a CB1R antagonist), and in CB1R knockdown mice in GABAergic neurons, but not glutamatergic neurons of the RAIC. Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.
Mice
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Animals
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Insular Cortex
;
Peroneal Nerve
;
Mice, Inbred C57BL
;
Neuralgia
;
GABAergic Neurons
;
Analgesia
;
Analgesics
;
Receptors, Cannabinoid
9.Reexamination of Dopaminergic Amacrine Cells in the Rabbit Retina: Confocal Analysis with Double- and Triple-labeling Immunohistochemistry.
Jong Woo LEE ; Min Young LIM ; Yong Soo PARK ; Su Jin PARK ; In Beom KIM
Experimental Neurobiology 2017;26(6):329-338
Dopaminergic amacrine cells (DACs) are among the most well-characterized neurons in the mammalian retina, and their connections to AII amacrine cells have been described in detail. However, the stratification of DAC dendrites differs based on their location in the inner plexiform layer (IPL), raising the question of whether all AII lobules are modulated by dopamine release from DACs. The present study aimed to clarify the relationship between DACs and AII amacrine cells, and to further elucidate the role of dopamine at synapses with AII amacrine cell. In the rabbit retina, DAC dendrites were observed in strata 1, 3, and 5 of the IPL. In stratum 1, most DAC dendritic varicosities—the presumed sites of neurotransmitter release—made contact with the somata and lobular appendages of AII amacrine cells. However, most lobular appendages of AII amacrine cells localized within stratum 2 of the IPL exhibited little contact with DAC varicosities. In addition, double- or triple-labeling experiments revealed that DACs did not express the GABAergic neuronal markers anti-GABA, vesicular GABA transporter, or glutamic acid decarboxylase. These findings suggest that the lobular appendages of AII amacrine cells are involved in at least two different circuits. We speculate that the circuit associated with stratum 1 of the IPL is modulated by DACs, while that associated with stratum 2 is modulated by unknown amacrine cells expressing a different neuroactive substance. Our findings further indicate that DACs in the rabbit retina do not use GABA as a neurotransmitter, in contrast to those in other mammals.
Amacrine Cells*
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Dendrites
;
Dopamine
;
GABAergic Neurons
;
gamma-Aminobutyric Acid
;
Glutamate Decarboxylase
;
Immunohistochemistry*
;
Mammals
;
Neurons
;
Neurotransmitter Agents
;
Retina*
;
Synapses
10.In Vivo Roles of a Patient-Derived Induced Pluripotent Stem Cell Line (HD72-iPSC) in the YAC128 Model of Huntington's Disease.
Iksoo JEON ; Chunggab CHOI ; Nayeon LEE ; Wooseok IM ; Manho KIM ; Seung Hun OH ; In Hyun PARK ; Hyun Sook KIM ; Jihwan SONG
International Journal of Stem Cells 2014;7(1):43-47
Induced pluripotent stem cells (iPSCs) generated from somatic cells of patients can provide immense opportunities to model human diseases, which may lead to develop novel therapeutics. Huntington's disease (HD) is a devastating neurodegenerative genetic disease, with no available therapeutic options at the moment. We recently reported the characteristics of a HD patient-derived iPSC carrying 72 CAG repeats (HD72-iPSC). In this study, we investigated the in vivo roles of HD72-iPSC in the YAC128 transgenic mice, a commonly used HD mouse model carrying 128 CAG repeats. To do this, we transplanted HD72-iPSC-derived neural precursors into the striatum of YAC128 mice bilaterally and observed a significant behavioral improvement in the grafted mice. Interestingly, the transplanted HD72-iPSC-derived neural precursors formed GABAeric neurons efficiently, but no EM48-positive protein aggregates were detected at 12 weeks after transplantation. Taken together, these results indicate no HD pathology was developed from the grafted cells, or no transmission of HD pathology from the host to the graft occurred at 12 weeks post-transplantation.
Animals
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GABAergic Neurons
;
Humans
;
Huntington Disease*
;
Induced Pluripotent Stem Cells
;
Mice
;
Mice, Transgenic
;
Neurons
;
Pathology
;
Pluripotent Stem Cells*
;
Transplants