Development of Cerebral Cortical GABaergic Neurons In Vitro

Substance P (SP) is implicated in stress regulation and affective and anxiety-related behavior. Particularly high expression has been found in the main output region of the amygdala complex, the central amygdala (CE). Here we investigated the cellular mechanisms of SP in CE in vitro, taking advantage of glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) knockin mice that yield a reliable labeling of GABAergic neurons, which comprise 95% of the neuronal population in the lateral section of CE (CEl). In GFP-positive neurons within CEl, SP caused a membrane depolarization and increase in input resistance, associated with an increase in action potential firing frequency. Under voltage-clamp conditions, the SP-specific membrane current reversed at −101.5 ± 2.8 mV and displayed inwardly rectifying properties indicative of a membrane K+ conductance. Moreover, SP responses were blocked by the neurokinin type 1 receptor (NK1R) antagonist L-822429 and mimicked by the NK1R agonist [Sar9,Met(O2)11]-SP. Immunofluorescence staining confirmed localization of NK1R in GFP-positive neurons in CEl, predominantly in PKCδ-negative neurons (80%) and in few PKCδ-positive neurons (17%). Differences in SP responses were not observed between the major types of CEl neurons (late firing, regular spiking, low-threshold bursting). In addition, SP increased the frequency and amplitude of GABAergic synaptic events in CEl neurons depending on upstream spike activity. These data indicate a NK1R-mediated increase in excitability and GABAergic activity in CEl neurons, which seems to mostly involve the PKCδ-negative subpopulation. This influence can be assumed to increase reciprocal interactions between CElon and CEloff pathways, thereby boosting the medial CE (CEm) output pathway and contributing to the anxiogenic-like action of SP in the amygdala.

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Hippocampal GABAergic Neurons are Susceptible to Amyloid-β Toxicity in vitro and are Decreased in Number in the Alzheimer's Disease TgCRND8 Mouse Model

Journal of Alzheimer s Disease ◽

10.3233/jad-2011-110830 ◽

2012 ◽

Vol 29 (2) ◽

pp. 293-308 ◽

Cited By ~ 30

Author(s):

Slavica Krantic ◽

Nathalie Isorce ◽

Naguib Mechawar ◽

Maria Antonietta Davoli ◽

Erika Vignault ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Amyloid Β ◽

Gabaergic Neurons ◽

Tgcrnd8 Mouse ◽

Toxicity In Vitro

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Acetylcholine excites GABAergic neurons of the ferret perigeniculate nucleus through nicotinic receptors

Journal of Neurophysiology ◽

10.1152/jn.1995.73.5.2123 ◽

1995 ◽

Vol 73 (5) ◽

pp. 2123-2128 ◽

Cited By ~ 20

Author(s):

K. H. Lee ◽

D. A. McCormick

Keyword(s):

Spike Activity ◽

Membrane Conductance ◽

Gabaergic Neurons ◽

Local Application ◽

Muscarinic Agonist ◽

Action Potential Firing ◽

Perigeniculate Nucleus ◽

Single Spike ◽

Hyperpolarizing Response

1. The actions of acetylcholine (ACh) on the GABAergic neurons of the perigeniculate nucleus (PGN) were investigated with the use of extra- and intracellular recording techniques in spontaneously spindling ferret thalamic slices maintained in vitro. 2. Local application of ACh to PGN neurons resulted in rapid depolarization followed by a longer lasting hyperpolarization. Neither of these responses were abolished by blockade of synaptic transmission with tetrodotoxin (TTX) nor with low Ca2+ and elevated Mg2+ solution, indicating that they are direct postsynaptic actions of ACh on PGN cells. Functionally, the rapid depolarizing response could activate both single spike activity, as well as low-threshold Ca2+ spike-mediated bursts. 3. The fast depolarizing response to ACh was selectively blocked by application of the nicotinic antagonist hexamethonium, whereas the slow hyperpolarizing response to ACh was selectively blocked by application of the muscarinic antagonist (-)scopolamine. Application of both hexamethonium and (-)scopolamine blocked the modulation of PGN action-potential firing by ACh. 4. Local application of the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) resulted in a depolarizing response and an increase in membrane conductance, whereas application of the muscarinic agonist DL-muscarine chloride resulted in a hyperpolarizing response and an increase in membrane conductance. When applied to spontaneously spindling PGN cells, both DMPP and DL-muscarine blocked the occurrence of spindle oscillations. However, only DMPP was associated with depolarization and the generation of single spike activity. 5. These results indicate that the GABAergic cells of the PGN possess postsynaptic nicotinic as well as muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

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GABAergic Neurons from Mouse Embryonic Stem Cells Possess Functional Properties of Striatal Neurons In Vitro, and Develop into Striatal Neurons In Vivo in a Mouse Model of Huntington’s Disease

Stem Cell Reviews and Reports ◽

10.1007/s12015-011-9290-2 ◽

2011 ◽

Vol 8 (2) ◽

pp. 513-531 ◽

Cited By ~ 23

Author(s):

Eunju Shin ◽

Mary J. Palmer ◽

Meng Li ◽

Rosemary A. Fricker

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Mouse Model ◽

Functional Properties ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Gabaergic Neurons ◽

Striatal Neurons

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P38 Initiates Diabetic Neurodegeneration Through Glutamatergic and GABAergic Neurons

10.21203/rs.3.rs-41603/v1 ◽

2020 ◽

Author(s):

Aisan Farhadi ◽

Mehdi Totonchi ◽

Seyed Masood Nabavi ◽

Hossein Baharvand ◽

Hossein Pakdaman ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Diabetic Mouse ◽

Gabaergic Neurons ◽

Expression Data ◽

Tau Pathology

Abstract Background: Diabetes mellitus may cause neurodegeneration, but the exact mechanism by which diabetic conditions induce neuronal cell death remains unclear. Tau protein hyperphosphorylation is considered to be a major pathological hallmark of neurodegeneration and can be triggered by diabetes. Various tau-directed kinases, including P38, can be activated upon diabetic stress and induce tau hyperphosphorylation. Despite extensive research efforts and the known importance of tau pathology in neurodegeneration, the exact tau specie(s) and kinases driving neurodegeneration in diabetes mellitus have not been clearly elucidated. Methods: We herein employed protein expression data analysis as well as immunofluorescence and immunoblotting techniques to determine the exact molecular mechanism of tau pathology triggered by diabetes in both in vitro and in vivo systems.Results: We found that P38, a major tau kinase, was increased in Glutamatergic & GABAergic neuron subtypes under diabetic conditions. This rendered them more responsive to oxidative stress caused by diabetes. We observed that oxidative stress activated P38, which in turn directly and indirectly drove tau pathology in the brainstem (enriched by Glutamatergic & GABAergic neurons), which gradually spread to neighboring brain areas. Notably, P38 inhibition suppressed tau pathogenicity and neurodegeneration in diabetic mouse models. Conclusion: The data establish P38 as a central mediator of diabetes mellitus induced tau pathology. Furthermore, the inhibition of P38 at early stages of diabetes-induced stress can inhibit tau pathology. Our findings provide mechanistic insight on the consequences of this metabolic disorder on the nervous system.

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Regional heterogeneity of developing GABAergic interneuron excitation in vivo

10.1101/701862 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yasunobu Murata ◽

Matthew T. Colonnese

Keyword(s):

Synapse Formation ◽

Critical Role ◽

Reversal Potential ◽

Pyramidal Cells ◽

Gabaergic Neurons ◽

Network Activity ◽

Gabaergic Interneuron ◽

Intact Brain

AbstractGABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are indeed excitatory in hippocampus at postnatal-day 3 (P3), and responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas cortical interneurons are inhibitory at P3 and remain so throughout development. This regional and age heterogeneity is the result of a change in chloride reversal potential as activation of light-gated anion channels expressed in glutamatergic neurons causes firing in hippocampus at P3, but silences it at P7. This study in the intact brain reveals a critical role for GABAergic interneuron excitation in neonatal hippocampus, and a surprising heterogeneity of interneuron function in cortical circuits that was not predicted from in vitro studies.

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Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

Molecular Psychiatry ◽

10.1038/s41380-020-00906-0 ◽

2020 ◽

Author(s):

Ya-Dong Li ◽

Yan-Jia Luo ◽

Wei Xu ◽

Jing Ge ◽

Yoan Cherasse ◽

...

Keyword(s):

Dopaminergic Neurons ◽

Gabaergic Neurons ◽

Population Activity ◽

Lateral Habenula ◽

Optogenetic Stimulation ◽

Ventral Tegmental ◽

Stimulation Of

Abstract The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

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