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1.
Belo Horizonte; s.n; 2023. 33 p.
Thesis in Portuguese | LILACS, InstitutionalDB, ColecionaSUS | ID: biblio-1435264

ABSTRACT

The medial prefrontal cortex (mPFC) is essential in the execution of cognitive tasks, however very little is known on how these neurons are modulated during specific tasks and which subtype of neurons are responsible for so. Therego, with the intention of addressing this issue, we recorded mPFC gabaergic and glutamatergic activation patterns through fiber photometry (FIP) in mice, while simultaneously performing the Barnes Maze (BM) cognitive task (4 day behavioral trial). In addition, an altered structural and procedural protocol for BM was validated in this study due to necessary modifications allowing FIP and BM to happen simultaneously. A successful protocol validation was followed by our preliminary results, which showed that both glutamatergic and gabaergic neurons presented significant change in activation intensity and number of events in specific contexts throughout the task days. In addition, when stratified and crossed with BM performance parameters, such as latency to complete tasks and adopted strategy, glutamatergic and gabaergic neurons presented a significant decline in both activation patterns and number of activation events throughout the days. This data suggest not only an important role of glutamatergic and gabaergic mPFC neurons in learning, memory and decision making, but also that activation patterns of each of these groups may serve as markers for cognitive progression and/or dysfunction. KEY-WORDS: Memory, Learning, Decision Making, Medial Prefrontal Cortex (mPFC), Fiber Photometry (FIP), Barnes Maze (BM), Glutamatergic, Gabaergic, Neuronal Activity, Neuronal Activation Patterns, Neuronal Dynamics.


O córtex pré-frontal medial (mPFC) é essencial na execução de tarefas cognitivas, no entanto, pouco se sabe sobre como esses neurônios são modulados durante tarefas específicas e qual subtipo de neurônios é responsável por isso. Portanto, com a intenção de abordar essa questão, registramos os padrões de ativação de neurônios gabaérgicos e glutamatérgicos do mPFC por meio de fotometria de fibra (FIP) em camundongos, enquanto realizávamos simultaneamente a tarefa cognitiva do Labirinto de Barnes (BM) (ensaio comportamental de 4 dias). Além disso, um protocolo estrutural e procedimental alterado para o BM foi validado neste estudo devido a modificações necessárias que permitiram a realização simultânea de FIP e BM. Uma validação bem-sucedida do protocolo foi seguida pelos nossos resultados preliminares, que mostraram que tanto os neurônios glutamatérgicos quanto os gabaérgicos apresentaram mudanças significativas na intensidade de ativação e no número de eventos em contextos específicos ao longo dos dias da tarefa. Além disso, quando estratificados e cruzados com parâmetros de desempenho do BM, como latência para completar as tarefas e estratégia adotada, os neurônios glutamatérgicos e gabaérgicos apresentaram uma diminuição significativa nos padrões de ativação e no número de eventos de ativação ao longo dos dias. Esses dados sugerem não apenas um papel importante dos neurônios glutamatérgicos e gabaérgicos do mPFC na aprendizagem, memória e tomada de decisões, mas também que os padrões de ativação de cada um desses grupos podem servir como marcadores de progressão e/ou disfunção cognitiva. PALAVRAS-CHAVE: Memória, Aprendizagem, Tomada de Decisões, Córtex Pré-Frontal Medial (mPFC), Fotometria de Fibra (FIP), Labirinto de Barnes (BM), Glutamatérgico, Gabaérgico, Atividade Neuronal, Padrões de Ativação Neuronal, Dinâmica Neuronal.


Subject(s)
Humans , Male , Female , Photometry , Prefrontal Cortex , Glutamic Acid , GABA Agents , Decision Making , Learning , Memory , GABAergic Neurons , Cognitive Dysfunction , Neurons
2.
Neuroscience Bulletin ; (6): 1348-1362, 2023.
Article in English | WPRIM | ID: wpr-1010610

ABSTRACT

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.


Subject(s)
Mice , Animals , Insular Cortex , Peroneal Nerve , Mice, Inbred C57BL , Neuralgia , GABAergic Neurons , Analgesia , Analgesics , Receptors, Cannabinoid
3.
Acta Physiologica Sinica ; (6): 369-378, 2023.
Article in Chinese | WPRIM | ID: wpr-981013

ABSTRACT

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.


Subject(s)
Mice , Male , Animals , Stress Disorders, Post-Traumatic , Hippocampus , Spatial Learning , GABAergic Neurons
4.
Article in Chinese | WPRIM | ID: wpr-986981

ABSTRACT

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.


Subject(s)
Male , Animals , Mice , Mice, Inbred C57BL , Propofol/pharmacology , Sevoflurane/pharmacology , Zona Incerta , Anesthesia, General , GABAergic Neurons
5.
Neuroscience Bulletin ; (6): 342-358, 2022.
Article in English | WPRIM | ID: wpr-929097

ABSTRACT

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.


Subject(s)
Animals , Rats , Anxiety/etiology , Chronic Pain/etiology , GABAergic Neurons , Gyrus Cinguli/metabolism , Hyperalgesia/metabolism , Pancreatitis, Chronic/pathology , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/metabolism , Trinitrobenzenesulfonic Acid/toxicity
6.
Neuroscience Bulletin ; (6): 263-274, 2022.
Article in English | WPRIM | ID: wpr-929087

ABSTRACT

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.


Subject(s)
Animals , Mice , Dopaminergic Neurons/physiology , GABAergic Neurons/physiology , Nucleus Accumbens/metabolism , Reward , Ventral Tegmental Area/metabolism
7.
Neuroscience Bulletin ; (6): 209-222, 2022.
Article in English | WPRIM | ID: wpr-929079

ABSTRACT

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.


Subject(s)
Humans , Amygdala/metabolism , Calbindin 2/metabolism , Epilepsy , GABAergic Neurons , Hippocampus/metabolism
8.
Neuroscience Bulletin ; (6): 497-506, 2019.
Article in English | WPRIM | ID: wpr-775419

ABSTRACT

Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.


Subject(s)
Animals , Cell Adhesion Molecules, Neuronal , Physiology , Cells, Cultured , Cerebral Cortex , Embryology , Physiology , GABAergic Neurons , Physiology , Interneurons , Physiology , Membrane Proteins , Physiology , Nerve Tissue Proteins , Physiology , Protein Isoforms , Physiology , Pyramidal Cells , Physiology , Rats, Sprague-Dawley , Synapses , Physiology
9.
Article in English | WPRIM | ID: wpr-727577

ABSTRACT

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of µ-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective µ-opioid agonist, [D-Ala², NMe-Phe⁴, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by K⁺ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.


Subject(s)
Animals , Mice , Analgesics, Opioid , Enkephalin, Ala(2)-MePhe(4)-Gly(5)- , Excitatory Postsynaptic Potentials , GABAergic Neurons , Interneurons , Mice, Transgenic , Nerve Fibers, Unmyelinated , Neurons , Spinal Cord , Spinal Cord Dorsal Horn , Substantia Gelatinosa , Synaptic Transmission
10.
Neuroscience Bulletin ; (6): 1029-1036, 2018.
Article in English | WPRIM | ID: wpr-775485

ABSTRACT

The ventral pallidum (VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion. Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamic-derived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.


Subject(s)
Animals , Female , Male , Rats , Action Potentials , Basal Forebrain , Cell Biology , Dimaprit , Pharmacology , Dose-Response Relationship, Drug , Electric Stimulation , GABAergic Neurons , Histamine , Pharmacology , Histamine Agonists , Pharmacology , Lysine , Metabolism , Patch-Clamp Techniques , Pyridines , Pharmacology , Rats, Sprague-Dawley , Receptors, Histamine H1 , Metabolism , Receptors, Histamine H2 , Metabolism , Sodium Channel Blockers , Pharmacology , Tetrodotoxin , Pharmacology , gamma-Aminobutyric Acid , Metabolism
11.
Neuroscience Bulletin ; (6): 485-496, 2018.
Article in English | WPRIM | ID: wpr-777034

ABSTRACT

The GABAergic neurons in the parafacial zone (PZ) play an important role in sleep-wake regulation and have been identified as part of a sleep-promoting center in the brainstem, but the long-range connections mediating this function remain poorly characterized. Here, we performed whole-brain mapping of both the inputs and outputs of the GABAergic neurons in the PZ of the mouse brain. We used the modified rabies virus EnvA-ΔG-DsRed combined with a Cre/loxP gene-expression strategy to map the direct monosynaptic inputs to the GABAergic neurons in the PZ, and found that they receive inputs mainly from the hypothalamic area, zona incerta, and parasubthalamic nucleus in the hypothalamus; the substantia nigra, pars reticulata and deep mesencephalic nucleus in the midbrain; and the intermediate reticular nucleus and medial vestibular nucleus (parvocellular part) in the pons and medulla. We also mapped the axonal projections of the PZ GABAergic neurons with adeno-associated virus, and defined the reciprocal connections of the PZ GABAergic neurons with their input and output nuclei. The newly-found inputs and outputs of the PZ were also listed compared with the literature. This cell-type-specific neuronal whole-brain mapping of the PZ GABAergic neurons may reveal the circuits underlying various functions such as sleep-wake regulation.


Subject(s)
Animals , Mice , Axons , Physiology , Brain , Brain Mapping , Brain Stem , Cell Biology , GABAergic Neurons , Physiology , Green Fluorescent Proteins , Genetics , Metabolism , Mice, Inbred C57BL , Mice, Transgenic , Neural Pathways , Physiology , Peptide Elongation Factor 1 , Genetics , Metabolism , Rabies virus , Genetics , Metabolism , Transduction, Genetic , Vesicular Inhibitory Amino Acid Transport Proteins , Genetics , Metabolism
12.
Experimental Neurobiology ; : 112-119, 2018.
Article in English | WPRIM | ID: wpr-714115

ABSTRACT

Aucubin is a small compound naturally found in traditional medicinal herbs with primarily anti-inflammatory and protective effects. In the nervous system, aucubin is reported to be neuroprotective by enhancing neuronal survival and inhibiting apoptotic cell death in cultures and disease models. Our previous data, however, suggest that aucubin facilitates neurite elongation in cultured hippocampal neurons and axonal regrowth in regenerating sciatic nerves. Here, we investigated whether aucubin facilitates the differentiation of neural precursor cells (NPCs) into specific types of neurons. In NPCs cultured primarily from the rat embryonic hippocampus, aucubin significantly elevated the number of GAD65/67 immunoreactive cells and the expression of GAD65/67 proteins was upregulated dramatically by more than three-fold at relatively low concentrations of aucubin (0.01 µM to 10 µM). The expression of both NeuN and vGluT1 of NPCs, the markers for neurons and glutamatergic cells, respectively, and the number of vGluT1 immunoreactive cells also increased with higher concentrations of aucubin (1 µM and 10 µM), but the ratio of the increases was largely lower than GAD expression and GAD immunoreactive cells. The GABAergic differentiation of pax6-expressing late NPCs into GABA-producing cells was further supported in cortical NPCs primarily cultured from transgenic mouse brains, which express recombinant GFP under the control of pax6 promoter. The results suggest that aucubin can be developed as a therapeutic candidate for neurodegenerative disorders caused by the loss of inhibitory GABAergic neurons.


Subject(s)
Animals , Mice , Rats , Axons , Brain , Cell Death , GABAergic Neurons , Hippocampus , Mice, Transgenic , Nervous System , Neurites , Neurodegenerative Diseases , Neurons , Plants, Medicinal , Sciatic Nerve
13.
Article in Chinese | WPRIM | ID: wpr-300829

ABSTRACT

Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy. In the network level, cholinergic projection neurons as well as their interaction with other neurons may regulate the development of epilepsy, especially the cholinergic circuit from basal forebrain to hippocampus, while cholinergic local interneurons have not been reported to be associated with epilepsy. With the development of optogenetics and other techniques, dissect and regulate cholinergic related epilepsy circuit has become a hotspot of epilepsy research.


Subject(s)
Humans , Acetylcholine , Physiology , Basal Forebrain , Pathology , Brain Chemistry , Genetics , Physiology , Cholinergic Neurons , Chemistry , Classification , Pathology , Physiology , Epilepsy , Genetics , Pathology , Epilepsy, Frontal Lobe , Genetics , GABAergic Neurons , Physiology , Hippocampus , Pathology , Mutation , Genetics , Physiology , Neurons , Non-Neuronal Cholinergic System , Genetics , Physiology , Receptors, Muscarinic , Genetics , Physiology , Receptors, Nicotinic , Genetics , Physiology , Synaptic Transmission , Genetics , Physiology
14.
Experimental Neurobiology ; : 329-338, 2017.
Article in English | WPRIM | ID: wpr-146669

ABSTRACT

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.


Subject(s)
Amacrine Cells , Dendrites , Dopamine , GABAergic Neurons , gamma-Aminobutyric Acid , Glutamate Decarboxylase , Immunohistochemistry , Mammals , Neurons , Neurotransmitter Agents , Retina , Synapses
15.
Article in Korean | WPRIM | ID: wpr-136447

ABSTRACT

Many sedatives are used clinically and include benzodiazepines, barbiturates, antihistamines, propofol, and alpha-2-agonist. Benzodiazepines activate GABA neuronal receptors in the brain and present sedating, hypnotic, anxiolytic, amnestic, and anticonvulsant effects, but low analgesic effects. Propofol induce sedative, anxiolytic, and amnestic effects but no analgesic effects. However, risks such as cardiopulmonary instability and hypotension must be considered during administration. Dexmedetomidine is a high selective alpha-2 agonist and has many advantages as a sedative. Patients under dexmedetomidine sedation awaken easily and are more likely to be cooperative. Risk of respiratory depression and cardiopulmonary instability is low as well. Additionally, dexmedetomidine decreases amount of analgesic needed during and after surgery, presenting analgesic effects. Dexmedetomidine also decreases risk of delirium. However, bradycardia may occur and biphasic effects on blood pressure may be observed during beginning of administration. Because of lengthy symptom onset and offset time, physicians should carefully control administration at the beginning and end of dexmedetomidine administration. The purpose of this review is to evaluate the efficacy and availability of dexmedetomidine in various clinical fields including sedation for critically ill patients, regional anesthesia, monitored anesthesia care for some invasive procedures, stabilization of heart in cardiac surgery or endoscopic procedures.


Subject(s)
Humans , Anesthesia , Anesthesia, Conduction , Barbiturates , Benzodiazepines , Blood Pressure , Bradycardia , Brain , Critical Illness , Delirium , Dexmedetomidine , GABAergic Neurons , Heart , Histamine Antagonists , Hypnotics and Sedatives , Hypotension , Propofol , Respiratory Insufficiency , Thoracic Surgery
16.
Article in Korean | WPRIM | ID: wpr-136446

ABSTRACT

Many sedatives are used clinically and include benzodiazepines, barbiturates, antihistamines, propofol, and alpha-2-agonist. Benzodiazepines activate GABA neuronal receptors in the brain and present sedating, hypnotic, anxiolytic, amnestic, and anticonvulsant effects, but low analgesic effects. Propofol induce sedative, anxiolytic, and amnestic effects but no analgesic effects. However, risks such as cardiopulmonary instability and hypotension must be considered during administration. Dexmedetomidine is a high selective alpha-2 agonist and has many advantages as a sedative. Patients under dexmedetomidine sedation awaken easily and are more likely to be cooperative. Risk of respiratory depression and cardiopulmonary instability is low as well. Additionally, dexmedetomidine decreases amount of analgesic needed during and after surgery, presenting analgesic effects. Dexmedetomidine also decreases risk of delirium. However, bradycardia may occur and biphasic effects on blood pressure may be observed during beginning of administration. Because of lengthy symptom onset and offset time, physicians should carefully control administration at the beginning and end of dexmedetomidine administration. The purpose of this review is to evaluate the efficacy and availability of dexmedetomidine in various clinical fields including sedation for critically ill patients, regional anesthesia, monitored anesthesia care for some invasive procedures, stabilization of heart in cardiac surgery or endoscopic procedures.


Subject(s)
Humans , Anesthesia , Anesthesia, Conduction , Barbiturates , Benzodiazepines , Blood Pressure , Bradycardia , Brain , Critical Illness , Delirium , Dexmedetomidine , GABAergic Neurons , Heart , Histamine Antagonists , Hypnotics and Sedatives , Hypotension , Propofol , Respiratory Insufficiency , Thoracic Surgery
17.
Yonsei Medical Journal ; : 165-172, 2016.
Article in English | WPRIM | ID: wpr-186108

ABSTRACT

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.


Subject(s)
Animals , Humans , Rats , Acetylcholine/metabolism , Alzheimer Disease , Antibodies, Monoclonal/pharmacology , Basal Forebrain/drug effects , Cholinergic Agents/administration & dosage , Cholinergic Neurons/drug effects , Fluorodeoxyglucose F18 , GABAergic Neurons/drug effects , Glucose/metabolism , Gyrus Cinguli/drug effects , Injections , Maze Learning , Motor Activity/physiology , Positron-Emission Tomography , Ribosome Inactivating Proteins, Type 1/pharmacology
18.
Article in Korean | WPRIM | ID: wpr-147140

ABSTRACT

Gephyrin is a central element that anchors, clusters and stabilizes glycine and gamma-aminobutyric acid type A receptors at inhibitory synapses of the mammalian brain. It self-assembles into a hexagonal lattice and interacts with various inhibitory synaptic proteins. Intriguingly, the clustering of gephyrin, which is regulated by multiple posttranslational modifications, is critical for inhibitory synapse formation and function. In this review, we summarize the basic properties of gephyrin and describe recent findings regarding its roles in inhibitory synapse formation, function and plasticity. We will also discuss the implications for the pathophysiology of brain disorders and raise the remaining open questions in this field.


Subject(s)
Animals , Humans , Carrier Proteins/chemistry , Disease Susceptibility , GABAergic Neurons/metabolism , Gene Expression Regulation , Membrane Proteins/chemistry , Protein Binding , Protein Interaction Domains and Motifs , Protein Processing, Post-Translational , Protein Transport , Synapses/metabolism
19.
Biomédica (Bogotá) ; 34(2): 207-217, abr.-jun. 2014. ilus, graf
Article in English | LILACS | ID: lil-712403

ABSTRACT

Introduction: Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. Objective: To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. Materials and methods: Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra. Results: We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus. Conclusion: Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.


Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fármaco neuroprotector prometedor para el tratamiento de la apoplejía; sin embargo, su acción sobre las poblaciones neuronales del sistema nigroestriatal después de la isquemia aún se desconoce. Objetivo. Evaluar el efecto de la atorvastatina sobre poblaciones gabérgicas y dopaminérgicas en regiones exofocales en un modelo de oclusión transitoria de la arteria cerebral media. Materiales y métodos. Se utilizaron 28 ratas Wistar macho de ocho semanas de edad. Los ejemplares con isquemia simulada y los ejemplares sometidos a isquemia fueron tratados con atorvastatina (10 mg/kg) y carboximetilcelulosa (placebo) administrados por medio de sonda a las 6, 24, 48 y 72 horas después de la reperfusión. Se analizó la inmunorreacción de la descarboxilasa del ácido glutámico y de la tirosina hidroxilasa en el globo pálido, el putamen caudado y la sustancia negra. Resultados. Los datos confirmaron el daño neurológico y la pérdida celular en el putamen caudado. Se incrementó la inmunorreacción de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata , disminuyendo la inmunorreacción de la descarboxilasa del ácido glutámico en el globo pálido lateral de los animales isquémicos tratados con placebo; sin embargo, el tratamiento con atorvastatina pudo revertirla, lo que logró una disminución significativa de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata y aumentando los niveles de descarboxilasa del ácido glutámico en el globo pálido lateral. Conclusión. Nuestros datos sugieren que la atorvastatina en el tratamiento posterior a la isquemia ejerce neuroprotección en las zonas exofocales, modulando las poblaciones neuronales gabérgicas y dopaminérgicas del sistema nigroestriatal, lo que podría prevenir trastornos neurológicos.


Subject(s)
Animals , Male , Rats , Corpus Striatum/drug effects , Dopaminergic Neurons/drug effects , GABAergic Neurons/drug effects , Heptanoic Acids/therapeutic use , Infarction, Middle Cerebral Artery/drug therapy , Ischemic Attack, Transient/drug therapy , Neuroprotective Agents/therapeutic use , Pyrroles/therapeutic use , Substantia Nigra/drug effects , Behavior, Animal , Corpus Striatum/blood supply , Corpus Striatum/pathology , Drug Evaluation, Preclinical , Dopaminergic Neurons/enzymology , Dopaminergic Neurons/pathology , Enzyme Induction/drug effects , GABAergic Neurons/enzymology , GABAergic Neurons/pathology , Glutamate Decarboxylase/biosynthesis , Glutamate Decarboxylase/genetics , Heptanoic Acids/pharmacology , Infarction, Middle Cerebral Artery/pathology , Ischemic Attack, Transient/pathology , Movement Disorders/etiology , Movement Disorders/prevention & control , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Neuroprotective Agents/pharmacology , Pyrroles/pharmacology , Rats, Wistar , Recovery of Function , Specific Pathogen-Free Organisms , Sensation Disorders/etiology , Sensation Disorders/prevention & control , Substantia Nigra/blood supply , Substantia Nigra/pathology , /biosynthesis , /genetics
20.
Article in English | WPRIM | ID: wpr-31116

ABSTRACT

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.


Subject(s)
Animals , Humans , Mice , GABAergic Neurons , Huntington Disease , Induced Pluripotent Stem Cells , Mice, Transgenic , Neurons , Pathology , Pluripotent Stem Cells , Transplants
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