scholarly journals Plasticity of GABAA receptor-mediated neurotransmission in the nucleus accumbens of alcohol-dependent rats

2014 ◽  
Vol 112 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Jing Liang ◽  
A. Kerstin Lindemeyer ◽  
Asha Suryanarayanan ◽  
Edward M. Meyer ◽  
Vincent N. Marty ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Rise Time ◽  
Neuronal Cell ◽  
Alcohol Exposure ◽  
Neuronal Cell Body ◽  
Body Volume ◽  
Gabaergic Neurotransmission ◽  
Chronic Intermittent Ethanol ◽  
Acid Type ◽  
Tonic Current

Chronic alcohol exposure-induced changes in reinforcement mechanisms and motivational state are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Here we describe the long-lasting alterations of γ-aminobutyric acid type A receptors (GABAARs) of medium spiny neurons (MSNs) in the NAcc after chronic intermittent ethanol (CIE) treatment, a rat model of alcohol dependence. CIE treatment and withdrawal (>40 days) produced decreases in the ethanol and Ro15-4513 potentiation of extrasynaptic GABAARs, which mediate the picrotoxin-sensitive tonic current ( Itonic), while potentiation of synaptic receptors, which give rise to miniature inhibitory postsynaptic currents (mIPSCs), was increased. Diazepam sensitivity of both Itonic and mIPSCs was decreased by CIE treatment. The average magnitude of Itonic was unchanged, but mIPSC amplitude and frequency decreased and mIPSC rise time increased after CIE treatment. Rise-time histograms revealed decreased frequency of fast-rising mIPSCs after CIE treatment, consistent with possible decreases in somatic GABAergic synapses in MSNs from CIE rats. However, unbiased stereological analysis of NeuN-stained NAcc neurons did not detect any decreases in NAcc volume, neuronal numbers, or neuronal cell body volume. Western blot analysis of surface subunit levels revealed selective decreases in α1 and δ and increases in α4, α5, and γ2 GABAAR subunits after CIE treatment and withdrawal. Similar, but reversible, alterations occurred after a single ethanol dose (5 g/kg). These data reveal CIE-induced long-lasting neuroadaptations in the NAcc GABAergic neurotransmission.

scholarly journals Selective modulation of GABAergic tonic current by dopamine in the nucleus accumbens of alcohol-dependent rats

2014 ◽  
Vol 112 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Jing Liang ◽  
Vincent N. Marty ◽  
Yatendra Mulpuri ◽  
Richard W. Olsen ◽  
Igor Spigelman
Keyword(s):  
Nucleus Accumbens ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Skf 38393 ◽  
Medium Spiny Neurons ◽  
Chronic Intermittent Ethanol ◽  
Acid Type ◽  
Tonic Current ◽  
Kinetics Of

The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system and plays an important role in mediating alcohol-seeking behaviors. Alterations in glutamatergic and GABAergic signaling were recently demonstrated in the NAcc of rats after chronic intermittent ethanol (CIE) treatment, a model of alcohol dependence. Here we studied dopamine (DA) modulation of GABAergic signaling and how this modulation might be altered by CIE treatment. We show that the tonic current ( Itonic) mediated by extrasynaptic γ-aminobutyric acid type A receptors (GABAARs) of medium spiny neurons (MSNs) in the NAcc core is differentially modulated by DA at concentrations in the range of those measured in vivo (0.01–1 μM), without affecting the postsynaptic kinetics of miniature inhibitory postsynaptic currents (mIPSCs). Use of selective D1 receptor (D1R) and D2 receptor (D2R) ligands revealed that Itonic potentiation by DA (10 nM) is mediated by D1Rs while Itonic depression by DA (0.03–1 μM) is mediated by D2Rs in the same MSNs. Addition of guanosine 5′- O-(2-thiodiphosphate) (GDPβS) to the recording pipettes eliminated Itonic decrease by the selective D2R agonist quinpirole (5 nM), leaving intact the quinpirole effect on mIPSC frequency. Recordings from CIE and vehicle control (CIV) MSNs during application of D1R agonist (SKF 38393, 100 nM) or D2R agonist (quinpirole, 2 nM) revealed that SKF 38393 potentiated Itonic to the same extent, while quinpirole reduced Itonic to a similar extent, in both groups of rats. Our data suggest that the selective modulatory effects of DA on Itonic are unaltered by CIE treatment and withdrawal.

scholarly journals Chronic Intermittent Ethanol and Lipopolysaccharide Exposure Differentially Alter Iba-1-Derived Microglia Morphology in the Prelimbic Cortex and Nucleus Accumbens Core

2019 ◽  
Author(s):  
BM Siemsen ◽  
JD Landin ◽  
JA McFaddin ◽  
KN Hooker ◽  
LJ Chandler ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Morphological Changes ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Confocal Imaging ◽  
Valuable Insight ◽  
Chronic Alcohol ◽  
Nucleus Accumbens Core ◽  
Structural Reorganization ◽  
Chronic Intermittent Ethanol

AbstractAccumulating evidence has linked pathological changes associated with chronic alcohol exposure to neuroimmune signaling mediated by microglia. Prior characterization of the microglial structure-function relationship demonstrates that alterations in activity states occur concomitantly with reorganization of cellular architecture. Accordingly, gaining a better understanding of microglial morphological changes associated with ethanol exposure will provide valuable insight into how neuroimmune signaling may contribute to ethanol-induced reshaping of neuronal function. Here we have used Iba-1-staining combined with high-resolution confocal imaging and 3D reconstruction to examine microglial structure in the prelimbic (PL) cortex and nucleus accumbens (NAc) in male Long-Evans rats. Rats were either sacrificed at peak withdrawal following 14 days of exposure to chronic intermittent ethanol (CIE) or 48 hours after exposure to the immune activator lipopolysaccharide (LPS). LPS exposure resulted in dramatic structural reorganization of microglia in the PL cortex; including increased soma volume, overall cellular volume, and branching complexity. In comparison, CIE exposure was associated with a subtle increase in somatic volume and differential effects on microglia processes, which were largely absent in the NAc. These data reveal that microglial activation following a neuroimmune challenge with LPS or exposure to chronic alcohol exhibit distinct morphometric profiles and brain-region dependent specificity.

scholarly journals Regulation of GABAA Receptor Subunit Expression in Substance Use Disorders

2020 ◽  
Vol 21 (12) ◽  
pp. 4445 ◽  
Author(s):  
Jeffrey Barker ◽  
Rochelle Hines
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Neuronal Cell ◽  
Alcohol Exposure ◽  
Receptor Expression ◽  
Adaptive Plasticity ◽  
Post Translational Modifications ◽  
Gabaergic Neurotransmission ◽  
Subunit Expression ◽  
Gabaar Subunit

The modulation of neuronal cell firing is mediated by the release of the neurotransmitter GABA (γ-aminobuytric acid), which binds to two major families of receptors. The ionotropic GABAA receptors (GABAARs) are composed of five distinct subunits that vary in expression by brain region and cell type. The action of GABA on GABAARs is modulated by a variety of clinically and pharmacologically important drugs such as benzodiazepines and alcohol. Exposure to and abuse of these substances disrupts homeostasis and induces plasticity in GABAergic neurotransmission, often via the regulation of receptor expression. Here, we review the regulation of GABAAR subunit expression in adaptive and pathological plasticity, with a focus on substance use. We examine the factors influencing the expression of GABAAR subunit genes including the regulation of the 5′ and 3′ untranslated regions, variations in DNA methylation, immediate early genes and transcription factors that regulate subunit expression, translational and post-translational modifications, and other forms of receptor regulation beyond expression. Advancing our understanding of the factors regulating GABAAR subunit expression during adaptive plasticity, as well as during substance use and withdrawal will provide insight into the role of GABAergic signaling in substance use disorders, and contribute to the development of novel targeted therapies.

Multiple Types of GABAA Receptors Mediate Inhibition in Brain Stem Parasympathetic Cardiac Neurons In the Nucleus Ambiguus

2006 ◽  
Vol 96 (6) ◽  
pp. 3266-3272 ◽  
Author(s):  
Euguenia Bouairi ◽  
Harriet Kamendi ◽  
Xin Wang ◽  
Christopher Gorini ◽  
David Mendelowitz
Keyword(s):  
Gaba Receptors ◽  
Nucleus Ambiguus ◽  
Resting Membrane Potential ◽  
Synaptic Currents ◽  
Gabaergic Neurotransmission ◽  
Acid Type ◽  
Different Types ◽  
Ambient Gaba ◽  
Tonic Current

Recent work suggests neurons can have different types of γ-aminobutyric acid type A (GABAA) receptors that mediate phasic inhibitory postsynaptic currents (IPSCs) and tonic currents. This study examines the diversity of GABAergic synaptic currents in parasympathetic cardioinhibitory neurons that receive rhythmic bursts of GABAergic neurotransmission. Focal application of gabazine (25 μM) to cardiac vagal neurons in vitro did not change the frequency of firing in spontaneously active neurons or the resting membrane potential; however, picrotoxin (100 μM) significantly depolarized cardiac vagal neurons and increased their firing. Similarly, gabazine (25 μM) selectively blocked GABAergic IPSCs but did not change holding current in cardiac vagal neurons, whereas picrotoxin (100 μM) not only blocked GABAergic IPSCs but also rapidly decreased the tonic current. Because the tonic current could be attributable to activation of GABA receptors by ambient GABA or, alternatively, spontaneous opening of constitutively active GABA channels, an antagonist for the GAT-1 GABA transporter NO-711 (10 μM) was applied to distinguish between these possibilities. NO-711 did not significantly alter the holding current in these neurons. The benzodiazepine flunitrazepam (1 μM) significantly increased the tonic current and GABAergic IPSC decay time; surprisingly, however, in the presence of gabazine flunitrazepam failed to elicit any change. These results suggest cardiac vagal neurons possess gabazine-sensitive GABAA receptors that mediate phasic synaptic currents, a gabazine-insensitive but picrotoxin-sensitive extrasynaptic tonic current that when blocked depolarizes and increases the firing rate of cardiac vagal neurons, and benzodiazepines recruit a third type of GABAA receptor that is sensitive to gabazine and augments the extrasynaptic tonic current.

Neurotransmission in neonatal rat cardiac ganglion in situ

1990 ◽  
Vol 259 (4) ◽  
pp. H997-H1005 ◽  
Author(s):  
G. R. Seabrook ◽  
L. A. Fieber ◽  
D. J. Adams
Keyword(s):  
Neuronal Cell ◽  
Nerve Fibers ◽  
Heart Beat ◽  
Neonatal Rat ◽  
Neuronal Cell Body ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Cardiac Ganglion ◽  
Cardiac Ganglia

The intrinsic cardiac ganglia of the neonatal rat heart in situ were studied using electrophysiological and histochemical techniques. The vagal branches innervating the atrial myocardium and cardiac ganglia were identified and individual ganglion cells visualized using Hoffman modulation contrast optics. Histochemical studies revealed the presence of acetylcholinesterase activity associated with neuronal cell bodies and fibers, catecholamine-containing, small intensely fluorescent cells, and cell bodies and nerve fibers immunoreactive for vasoactive intestinal polypeptide. Intracellular recordings from the "principal" cells of the rat cardiac ganglion in situ revealed a fast excitatory postsynaptic potential (EPSP) evoked after electrical stimulation of the vagus nerve, which was inhibited by the nicotinic receptor antagonist, mecamylamine. No spontaneously firing neurons were found, although infrequent (less than 2 min-1) spontaneous miniature EPSPs were observed in most neurons. The quantal content of neurally evoked responses was between 10 and 30 quanta, and the presence of multiple EPSPs in some cells suggested polyneuronal innervation. The neurally evoked EPSP amplitude was dependent on the rate of nerve stimulation, decreasing with increasing frequency of stimulation. Neurons exhibited a sustained depolarization during high frequency stimulation (greater than 1 Hz), and in approximately 15% of the cells a slow depolarization lasting 1-3 min was observed after a train of stimuli. The presence of catecholamine- and neuropeptide-containing neuronal cell body fibers in neonatal rat cardiac ganglia in situ, along with neurally evoked postsynaptic responses resistant to cholinergic ganglionic blockers, suggests a role for noncholinergic transmission in the regulation of the mammalian heart beat.

Separation of a process from the neuronal cell body using a thin aluminum foil separator

1998 ◽  
Vol 2 (4) ◽  
pp. 352-356 ◽  
Author(s):  
Kosuke Noda ◽  
Keita Jimbo ◽  
Kazuo Suzuki ◽  
Kentaro Yoda
Keyword(s):  
Cell Body ◽  
Neuronal Cell ◽  
Aluminum Foil ◽  
Neuronal Cell Body ◽  
Thin Aluminum ◽  
Thin Aluminum Foil

scholarly journals Differences in splicing defects between the grey and white matter in myotonic dystrophy type 1

2019 ◽  
Author(s):  
Masamitsu Nishi ◽  
Takashi Kimura ◽  
Mitsuru Furuta ◽  
Koichi Suenaga ◽  
Tsuyoshi Matsumura ◽  
...  
Keyword(s):  
White Matter ◽  
Myotonic Dystrophy ◽  
Cell Body ◽  
Neuronal Cell ◽  
Neuronal Cell Body ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
And Control ◽  
The Brain

AbstractMyotonic dystrophy type 1 (DM1) is a multi-system disorder caused by CTG repeats in the myotonic dystrophy protein kinase (DMPK) gene. This leads to sequestration of the splicing factor, muscleblind-like 2 (MBNL2), and aberrant splicing, mainly in the central nervous system. We investigated the splicing patterns of MBNL1/2 and genes controlled by MBNL2 in several regions of the brain and between the grey matter (GM) and white matter (WM) in DM1 patients using RT-PCR. Compared with the control, the percentage of spliced-in parameter (PSI) for most of the examined exons were significantly altered in most of the brain regions of DM1 patients, except for the cerebellum. The splicing of many genes was differently regulated between the GM and WM in both DM1 and control. The level of change in PSI between DM1 and control was higher in the GM than in the WM. The differences in alternative splicing between the GM and WM may be related to the effect of DM1 on the WM of the brain. We hypothesize that in DM1, aberrantly spliced isoforms in the neuronal cell body of the GM may not be transported to the axon. This might affect the WM as a consequence of Wallerian degeneration secondary to cell body damage. Our findings may have implications for analysis of the pathological mechanisms and exploring potential therapeutic targets.

scholarly journals Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Nolwazi Z. Gcwensa ◽  
Drèson L. Russell ◽  
Rita M. Cowell ◽  
Laura A. Volpicelli-Daley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Disease Onset ◽  
Neuronal Cell ◽  
Rem Sleep Behavior Disorder ◽  
Dopamine Neurons ◽  
Neuronal Cell Body ◽  
Substantia Nigra Pars Compacta ◽  
Cognitive Changes

Parkinson’s disease (PD) is a progressive neurodegenerative disease that impairs movement as well as causing multiple other symptoms such as autonomic dysfunction, rapid eye movement (REM) sleep behavior disorder, hyposmia, and cognitive changes. Loss of dopamine neurons in the substantia nigra pars compacta (SNc) and loss of dopamine terminals in the striatum contribute to characteristic motor features. Although therapies ease the symptoms of PD, there are no treatments to slow its progression. Accumulating evidence suggests that synaptic impairments and axonal degeneration precede neuronal cell body loss. Early synaptic changes may be a target to prevent disease onset and slow progression. Imaging of PD patients with radioligands, post-mortem pathologic studies in sporadic PD patients, and animal models of PD demonstrate abnormalities in presynaptic terminals as well as postsynaptic dendritic spines. Dopaminergic and excitatory synapses are substantially reduced in PD, and whether other neuronal subtypes show synaptic defects remains relatively unexplored. Genetic studies implicate several genes that play a role at the synapse, providing additional support for synaptic dysfunction in PD. In this review article we: (1) provide evidence for synaptic defects occurring in PD before neuron death; (2) describe the main genes implicated in PD that could contribute to synapse dysfunction; and (3) show correlations between the expression of Snca mRNA and mouse homologs of PD GWAS genes demonstrating selective enrichment of Snca and synaptic genes in dopaminergic, excitatory and cholinergic neurons. Altogether, these findings highlight the need for novel therapeutics targeting the synapse and suggest that future studies should explore the roles for PD-implicated genes across multiple neuron types and circuits.

Form and Function in Cells of the Brain

The Neuron ◽  
2015 ◽  
pp. 23-38
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek
Keyword(s):  
Axonal Transport ◽  
Molecular Motors ◽  
Critical Role ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Cell Body ◽  
Long Distance ◽  
Form And Function ◽  
And Function ◽  
The Brain

This chapter examines unique mechanisms that the neuron has evolved to establish and maintain the form required for its specialized signaling functions. Unlike some other organs, the brain contains a variety of cell types including several classes of glial cells, which play a critical role in the formation of the myelin sheath around axons and may be involved in immune responses, synaptic transmission, and long-distance calcium signaling in the brain. Neurons share many features in common with other cells (including glia), but they are distinguished by their highly asymmetrical shapes. The neuronal cytoskeleton is essential for establishing this cell shape during development and for maintaining it in adulthood. The process of axonal transport moves vesicles and other organelles to regions remote from the neuronal cell body. Proteins such as kinesin and dynein, called molecular motors, make use of the energy released by hydrolysis of ATP to drive axonal transport.

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