Mouse spinal cord in cell culture. III. Neuronal chemosensitivity and its relationship to synaptic activity

1. Mouse spinal cord (SC) cells in dissociated cell cultures showed strong electrophysiologic responses to glutamate, gamma-aminobutyric acid (GABA), and glycine when these were iontophoretically applied to the neurons. 2. The extrapolated reversal potential for the glutamate response was 20-30 mV negative in contrast to the positive extrapolated reversal potential for the SC-SC excitatory postsynaptic potential. The data are interpreted as indicating different ionic mechanisms for the glutamate response and the EPSP. 3. The reversal potentials for the glycine and GABA responses were similar to one another and to the IPSP reversal potential. The time course of the glycine and GABA responses were quite different from each other, however. 4. While some SC cells showed a relatively uniform sensitivity over their surfaces to iontophoretically applied glutamate, discrete regions of higher sensitivity occurred on most cells. 5. Release of excitatory and inhibitory transmitter could be elicited by focal application of glutamate and, in favorable instances, this could be shown to be due to the sensitivity of presynaptic terminals to the applied glutamate. Considerable spatial resolution of regions from which transmitter release could be elicited was achieved by this technique. Some correspondence between glutamate "hot spots" and such release sites was found.

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Synchronization properties of spindle oscillations in a thalamic reticular nucleus model

Journal of Neurophysiology ◽

10.1152/jn.1994.72.3.1109 ◽

1994 ◽

Vol 72 (3) ◽

pp. 1109-1126 ◽

Cited By ~ 120

Author(s):

D. Golomb ◽

X. J. Wang ◽

J. Rinzel

Keyword(s):

Time Course ◽

Cluster State ◽

Large Population ◽

Reversal Potential ◽

Ionic Currents ◽

Thalamic Reticular Nucleus ◽

Reticular Nucleus ◽

Quiescent State ◽

Gamma Aminobutyric Acid ◽

Cluster States

1. We address the hypothesis of Steriade and colleagues that the thalamic reticular nucleus (RE) is a pacemaker for thalamocortical spindle oscillations by developing and analyzing a model of a large population of all-to-all coupled inhibitory RE neurons. 2. Each RE neuron has three ionic currents: a low-threshold T-type Ca2+ current (ICa-T), a calcium-activated potassium current (IAHP) and a leakage current (IL). ICa-T underlies a cell's postinhibitory rebound properties, whereas IAHP hyperpolarizes the neuron after a burst. Each neuron, which is a conditional oscillator, is coupled to all other RE neurons via fast gamma-aminobutyric acid-A (GABAA) and slow GABAB synapses. 3. For generating network oscillations IAHP may not be necessary. Synaptic inhibition can provide the hyperpolarization for deinactivating ICa-T that causes bursting if the reversal potentials for GABAA and GABAB synapses are sufficiently negative. 4. If model neurons display sufficiently powerful rebound excitability, an isolated RE network of such neurons oscillates with partial but typically not full synchrony. The neurons spontaneously segregate themselves into several macroscopic clusters. The neurons within a cluster follow the same time course, but the clusters oscillate differently from one another. In addition to activity patterns in which clusters burst sequentially (e.g., 2 or 3 clusters bursting alternately), a two-cluster state may occur with one cluster active and one quiescent. Because the neurons are all-to-all coupled, the cluster states do not have any spatial structure. 5. We have explored the sensitivity of such partially synchronized patterns to heterogeneity in cells' intrinsic properties and to simulated neuroelectric noise. Although either precludes precise clustering, modest levels of heterogeneity or noise lead to approximate clustering of active cells. The population-averaged voltage may oscillate almost regularly but individual cells burst at nearly every second cycle or less frequently. The active-quiescent state is not robust at all to heterogeneity or noise. Total asynchrony is observed when heterogeneity or noise is too large, e.g., even at 25% heterogeneity for our reference set of parameter values. 6. The fast GABAA inhibition (with a reversal potential more negative than, say, -65 mV) favors the cluster states and prevents full synchrony. Our simulation results suggest two mechanisms that can fully synchronize the isolated RE network model. With GABAA removed or almost totally blocked, GABAB inhibition (because it is slow) can lead to full synchrony, which is partially robust to heterogeneity and noise.(ABSTRACT TRUNCATED AT 400 WORDS)

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Enflurane Actions on Spinal Cords from Mice That Lack the β3Subunit of the GABAAReceptor

Anesthesiology ◽

10.1097/00000542-200107000-00026 ◽

2001 ◽

Vol 95 (1) ◽

pp. 154-164 ◽

Cited By ~ 35

Author(s):

Shirley M. E. Wong ◽

Gong Cheng ◽

Gregg E. Homanics ◽

Joan J. Kendig

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Dominant Role ◽

Glycine Receptor ◽

Excitatory Postsynaptic Potential ◽

Evoked Responses ◽

Gamma Aminobutyric Acid ◽

Gaba A ◽

Root Potential ◽

Beta3 Subunit

Background Gamma-aminobutyric acid type A (GABA(A)) receptors are considered important in mediating anesthetic actions. Mice lacking the beta3 subunit of this receptor (beta3-/-) have a higher enflurane minimum alveolar concentration (MAC) than wild types (+/+). MAC is predominantly determined in spinal cord. Methods The authors measured three population-evoked responses in whole spinal cords, namely, the excitatory postsynaptic potential (pEPSP), the slow ventral root potential (sVRP), and the dorsal root potential. Synaptic and glutamate-evoked currents from motor neurons in spinal cord slices were also measured. Results Sensitivity of evoked responses to enflurane did not differ between +/+ and -/- cords. The GABA(A) receptor antagonist bicuculline significantly (P < 0.05) attenuated the depressant effects of enflurane on pEPSP, sVRP and glutamate-evoked currents in +/+ but not -/- cords. The glycine antagonist strychnine elevated the pEPSP to a significantly greater extent in -/- than in +/+ cords, but the interactions between strychnine and enflurane did not differ between -/- and +/+ cords. Conclusions Similar enflurane sensitivity in spinal cords from -/- and +/+ mice was coupled with a decreased role for GABA(A) receptors in mediating the actions of enflurane in the former. This finding implies that other anesthetic targets substitute for GABA(A) receptors. Increase in glycine receptor-mediated inhibition was found in -/- cords, but the glycine receptor does not appear to be a substitute anesthetic target. This mutation thus led to a quantitative change in the molecular basis for anesthetic depression of spinal neurotransmission in a fashion not predicted by the mutation itself. The results argue against an immutable dominant role for GABA(A) receptors in mediating spinal contributions to MAC.

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Effects of baclofen on transient neurons in the mudpuppy retina: electrogenic and network actions

Journal of Neurophysiology ◽

10.1152/jn.1989.61.2.382 ◽

1989 ◽

Vol 61 (2) ◽

pp. 382-390 ◽

Cited By ~ 16

Author(s):

S. H. Bai ◽

M. M. Slaughter

Keyword(s):

Driving Force ◽

Network Effects ◽

Ganglion Cells ◽

Control Process ◽

Light Response ◽

Bipolar Cells ◽

Excitatory Postsynaptic Potential ◽

Gamma Aminobutyric Acid ◽

Additional Input ◽

Inhibitory Transmitter

1. Baclofen increases transient light responses of amacrine and ganglion cells despite acting as a classical inhibitory transmitter to both hyperpolarize and shunt these cells. 2. This effect seems to occur at the level of the inner retina and appears not to be due to an additional input from bipolar cells. 3. In some transient cells baclofen increases the total amplitude of the light response but does not change the peak potential of the light evoked EPSP. In these cells, the baclofen-induced enhancement can be accounted for by an increase in driving force of the excitatory postsynaptic potential (EPSP) resulting from the hyperpolarization. 4. However, in other cells the peak of the light response after baclofen application is greater, which cannot be accounted for by a change in driving force. This effect of baclofen can be mimicked by a blockers of gamma-aminobutyric acid (GABA) and glycine, suggesting that in these cells baclofen's enhancement is due in part to network effects resulting in a removal of sustained inhibition. 5. Therefore, the paradoxical effect of an inhibitory transmitter producing an enhancement of synaptic responses seems due to at least two mechanisms. 6. The results indicate that some transient cells receive significant tonic inhibition which limits their response amplitude in a push-pull type mechanism, but other cells are not under this inhibitory control process.

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GABA as an inhibitory neurotransmitter in human cerebral cortex

Journal of Neurophysiology ◽

10.1152/jn.1989.62.5.1018 ◽

1989 ◽

Vol 62 (5) ◽

pp. 1018-1027 ◽

Cited By ~ 321

Author(s):

D. A. McCormick

Keyword(s):

Cerebral Cortex ◽

Cortical Neurons ◽

Epileptiform Activity ◽

Reversal Potential ◽

Membrane Conductance ◽

Pyramidal Cells ◽

Excitatory Postsynaptic Potential ◽

Gamma Aminobutyric Acid ◽

Human Cerebral Cortex ◽

Inhibitory Neurotransmitter

1. The possible role of gamma-aminobutyric acid (GABA) as an inhibitory neurotransmitter in the human cerebral cortex was investigated with the use of intracellular recordings from neocortical slices maintained in vitro. 2. Electrical stimulation of afferents to presumed pyramidal cells resulted in an initial excitatory postsynaptic potential (EPSP) followed by fast and slow inhibitory postsynaptic potentials (IPSPs). The early IPSP had an average reversal potential of -68 mV, was associated with a mean 67-nS increase in membrane conductance, was reduced by the GABAA antagonist bicuculline, was sensitive to the intracellular injection of Cl-, and was mimicked by the GABAA agonist muscimol. 3. The late IPSP, in contrast, had an average reversal potential of -95 mV, was associated with a mean 12-nS increase in membrane conductance, was reduced by the GABAB antagonist phaclofen, and was mimicked by the GABAB agonist baclofen. 4. Block of the early IPSP by bicuculline or picrotoxin led to the generation of paroxysmal epileptiform activity, which could be further enhanced by reduction of the late IPSP. 5. These data strongly support the hypothesis that GABA is a major inhibitory neurotransmitter in the human cerebral cortex and that GABAergic IPSPs play an important role in controlling the excitability and responsiveness of cortical neurons.

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Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord

International Journal of Molecular Sciences ◽

10.3390/ijms23020834 ◽

2022 ◽

Vol 23 (2) ◽

pp. 834

Author(s):

Chigusa Shimizu-Okabe ◽

Shiori Kobayashi ◽

Jeongtae Kim ◽

Yoshinori Kosaka ◽

Masanobu Sunagawa ◽

...

Keyword(s):

Spinal Cord ◽

Radial Glia ◽

Ventricular Zone ◽

Glycine Receptor ◽

Ventral Horn ◽

Gabaergic Neurons ◽

Inhibitory Neurons ◽

Gamma Aminobutyric Acid ◽

Mouse Spinal Cord ◽

Mature Mouse

Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine coreleasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play critical roles in regulating pain, locomotive movement, and respiratory rhythms. In this study, we first describe GABAergic and glycinergic transmission and inhibitory networks, consisting of three types of terminals in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with a specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated, and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many GABAergic neurons convert to a coreleasing state. The coreleasing neurons and terminals remain in the dorsal horn, whereas many ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.

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Inhibitory transmission in the basolateral amygdala

Journal of Neurophysiology ◽

10.1152/jn.1991.66.3.999 ◽

1991 ◽

Vol 66 (3) ◽

pp. 999-1009 ◽

Cited By ~ 138

Author(s):

D. G. Rainnie ◽

E. K. Asprodini ◽

P. Shinnick-Gallagher

Keyword(s):

Reversal Potential ◽

Nmda Antagonist ◽

Gabab Receptors ◽

Excitatory Postsynaptic Potential ◽

Sodium Pentobarbital ◽

Gamma Aminobutyric Acid ◽

Gabaa Receptor Antagonist ◽

Basolateral Nucleus ◽

Stimulation Of ◽

Synaptic Responses

1. Intracellular recording techniques were used to characterize synaptic inhibitory postsynaptic potentials (IPSPs) recorded from neurons of the basolateral nucleus of the amygdala (BLA). Bipolar electrodes positioned in the stria terminalis (ST) or lateral amygdala (LA) were used to evoke synaptic responses at a frequency of 0.25 Hz. 2. Two synaptic waveforms having IPSP components could be evoked by electrical stimulation of either pathway: a biphasic, excitatory postsynaptic potential (EPSP), fast-IPSP (f-IPSP) waveform, and a multiphasic, EPSP, f-IPSP, and subsequent slow-IPSP (s-IPSP) waveform. Expression of either waveform was dependent on the site of stimulation. ST stimulation evoked a similar number of biphasic (45%) and multiphasic (50%) synaptic responses. In contrast, stimulation of the LA pathway evoked mainly (80%) multiphasic synaptic responses. 3. Both the f- and s-IPSP elicited by ST stimulation could be reduced in amplitude in the presence of the glutamatergic, N-methyl-D-aspartate (NMDA) antagonist, (DL)-2-amino-5-phosphonovaleric acid (APV, 50 microM), and were abolished by the glutamatergic, non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). In contrast, a CNQX-resistant f-IPSP was evoked with LA stimulation and abolished by subsequent addition of bicuculline methiodide (BMI), a gamma-aminobutyric acid (GABAA) receptor antagonist, suggesting direct inhibition of BLA neurons by GABAergic LA interneurons. The sensitivity of the s-IPSPs and the f-IPSPs to glutamatergic antagonists suggests the presence of feed-forward inhibition onto BLA neurons. 4. The f-IPSP possessed characteristics of potentials mediated by GABAA receptors linked to Cl- channels, namely, a reversal potential of -70 mV, a decrease in membrane resistance (13.5 M omega) recorded at -60 mV, a block by BMI, and potentiation by sodium pentobarbital (NaPB). 5. The s-IPSP was associated with a resistance decrease of 4.5 M omega, a reversal potential of -95 mV, and was reversibly depressed (approximately 66%) by 2-hydroxy-saclofen (100 microM), suggesting activation of GABAB receptors. 6. The large resistance change associated with the f-IPSP, its temporal overlap with evoked EPSPs, and the development of both spontaneous and evoked burst firing in the presence of BMI suggests that the f-IPSP determines the primary state of excitability in BLA neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord

10.20944/preprints202112.0469.v1 ◽

2021 ◽

Author(s):

Chigusa Shimizu-Okabe ◽

Shiori Kobayashi ◽

Jeongtae Kim ◽

Yoshinori Kosaka ◽

Masanobu Sunagawa ◽

...

Keyword(s):

Spinal Cord ◽

Radial Glia ◽

Ventricular Zone ◽

Glycine Receptor ◽

Ventral Horn ◽

Gabaergic Neurons ◽

Inhibitory Neurons ◽

Gamma Aminobutyric Acid ◽

Mouse Spinal Cord ◽

Mature Mouse

Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine co-releasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play key roles in the regulation of pain, locomotive movement, and respiratory rhythms. Herein, we first describe GABAergic and glycinergic transmission and inhibitory networks, which consist of three types of terminals, in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many of GABAergic neurons convert to co-releasing state. The co-releasing neurons and terminals remain in the dorsal horn, whereas many of co-releasing ones ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.

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The extent, time course, and fraction size dependence of mouse spinal cord recovery from radiation injury

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/0360-3016(92)90947-g ◽

1994 ◽

Vol 30 (3) ◽

pp. 609-617 ◽

Cited By ~ 20

Author(s):

Roberts Lavey ◽

Jeremy M.G. Taylor ◽

Jonathan D. Tward ◽

Leon T. Li ◽

Ann A. Nguyen ◽

...

Keyword(s):

Spinal Cord ◽

Time Course ◽

Size Dependence ◽

Radiation Injury ◽

Mouse Spinal Cord ◽

Fraction Size

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Mouse spinal cord in cell culture. II. Synaptic activity and circuit behavior

Journal of Neurophysiology ◽

10.1152/jn.1977.40.5.1151 ◽

1977 ◽

Vol 40 (5) ◽

pp. 1151-1162 ◽

Cited By ~ 55

Author(s):

B. R. Ransom ◽

C. N. Christian ◽

P. N. Bullock ◽

P. G. Nelson

Keyword(s):

Spinal Cord ◽

Dorsal Root ◽

Electrical Coupling ◽

Recording System ◽

Synaptic Activity ◽

Ion Concentration ◽

Equilibrium Potential ◽

Mouse Spinal Cord ◽

Synaptic Circuits ◽

Quantal Size

1. Neurons in cell cultures of fetal mouse spinal cord (SC) and dorsal root ganglia (DRG) develop extensive synaptic interconnections. 2. No spontaneous synaptic activity was detectable in the presence of tetrodotoxin or an elevated magnsium ion concentration, but statistical analysis of evoked excitatory postsynaptic potentials (EPSPs) indicates that the quantal size was 200-250 muV, which was below the noise level of the recording system used. 3. In a sample of eight RDG-SC and seven SC-SC cell pairs linked by EPSPs, the quantal content of the SC-SC EPSPs was about 3.5-fold larger than for the DRG-SC EPSPs. 4. The extrapolated equilibrium potential for the SC-SC EPSP was about 20 mV positive. The IPSP reversed at a membrane potential of 60-80 mV negative. 5. Some examples of the types of synaptic circuits commonly encountered are given. Only one case of electrical coupling between neurons was found.

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