Diurnal properties of Tonic and Synaptic GABAA receptor-mediated currents in Suprachiasmatic Nucleus neurons

2021 ◽  
Author(s):  
Michael Moldavan ◽  
Olga Cravetchi ◽  
Charles N Allen
Keyword(s):  
Charge Transfer ◽  
Suprachiasmatic Nucleus ◽  
Low Frequency ◽  
Cell Voltage ◽  
Gaba Release ◽  
Diurnal Rhythms ◽  
Equilibrium Potential ◽  
Critical Component ◽  
Gabaergic Synapses ◽  
Tonic Current

Synaptic and extrasynaptic GABAA receptor (GABAAR)-mediated neurotransmission is a critical component of the suprachiasmatic nucleus (SCN) neuronal network. However, the properties of the GABAA tonic current (Itonic) and its origin remain unexplored. Spontaneous GABAA postsynaptic currents (sGPSC) and Itonic were recorded from SCN neurons using the whole-cell voltage-clamp technique at different times of the day. GABAAR antagonists (bicuculline, gabazine, and picrotoxin) inhibited sGPSC and induced an outward shift of the holding current, which defined the Itonic amplitude. The sGPSC frequency, synaptic charge transfer, and the Itonic amplitude all demonstrated significant diurnal rhythms with peaks in the middle of the day (Zeitgeber Time, ZT8) and nadirs at night (ZT19). The Itonic amplitude increased proportionally with the sGPSC frequency and synaptic charge transfer during the day and required action potential-mediated GABA release, which was confirmed by TTX application. The activation of presynaptic GABAB receptors by baclofen did not significantly alter the Itonic of neurons with low-frequency sGPSC. The equilibrium potential (Eq) for Itonic was similar to the Eq for chloride and GABAA receptor-activated currents. Itonic showed outward rectification at membrane potentials over the range of -70 mV to -10 mV, then was linear at voltages greater than -10 mV. GABAAR containing α4-, α5- and δ- subunits were expressed in SCN, and their contribution to Itonic was confirmed by application of the GABAAR agonist THIP and the GABAAR inverse agonist L655,708. Thus, the Itonic was mediated by extrasynaptic GABAARs activated predominantly by GABA diffusing out of GABAergic synapses.

Synaptically Released GABA Activates Both Pre- and Postsynaptic GABAB Receptors in the Rat Globus Pallidus

2005 ◽  
Vol 94 (2) ◽  
pp. 1104-1114 ◽  
Author(s):  
Katsuyuki Kaneda ◽  
Hitoshi Kita
Keyword(s):  
Globus Pallidus ◽  
Reversal Potential ◽  
Gaba Release ◽  
Gabab Receptors ◽  
Equilibrium Potential ◽  
Postsynaptic Currents ◽  
Gabaergic Synapses ◽  
Rat Brain Slice ◽  
Whole Cell Recordings ◽  
Local Stimulation

The globus pallidus (GP) contains abundant GABAergic synapses and GABAB receptors. To investigate whether synaptically released GABA can activate pre- and postsynaptic GABAB receptors in the GP, physiological recordings were performed using rat brain slice preparations. Cell-attached recordings from GABAA antagonist-treated preparations revealed that repetitive local stimulation induced a GABAB antagonist-sensitive pause in spontaneous firings of GP neurons. Whole cell recordings revealed that the repetitive stimulation evoked fast excitatory postsynaptic potentials followed by a slow inhibitory postsynaptic potential (IPSP) in GP neurons. The slow IPSP was insensitive to a GABAA receptor antagonist, increased in amplitude with the application of ionotropic glutamate receptor antagonists, and was suppressed by the GABAB antagonist CGP55845 . The reversal potential of the slow IPSP was close to the potassium equilibrium potential. These results suggest that synaptically released GABA activated postsynaptic GABAB receptors and induced the pause and the slow IPSP. On the other hand, in the neurons that were treated to block postsynaptic GABAB responses, CGP55845 increased the amplitudes of repetitive local stimulation-induced GABAA-mediated inhibitory postsynaptic currents (IPSCs) but not the ionotropic glutamate-mediated excitatory postsynaptic currents. Moreover, the GABAB receptor specific agonist baclofen reduced the frequency of miniature IPSCs without altering their amplitude distributions. These results suggest that synaptically released GABA also activated presynaptic GABAB autoreceptors, resulting in decreased GABA release in the GP. Together, we infer that both pre- and postsynaptic GABAB receptors may play crucial roles in the control of GP neuronal activity.

scholarly journals GABA transporters regulate tonic and synaptic GABAA receptor-mediated currents in the suprachiasmatic nucleus neurons

2017 ◽  
Vol 118 (6) ◽  
pp. 3092-3106 ◽  
Author(s):  
Michael Moldavan ◽  
Olga Cravetchi ◽  
Charles N. Allen
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Dependent Manner ◽  
Circadian Period ◽  
Gaba Concentration ◽  
Gaba Transporter ◽  
Concentration Dependent Manner ◽  
Gaba Transport ◽  
Gaba Transporters ◽  
Tonic Current

GABA is a principal neurotransmitter in the hypothalamic suprachiasmatic nucleus (SCN) that contributes to intercellular communication between individual circadian oscillators within the SCN network and the stability and precision of the circadian rhythms. GABA transporters (GAT) regulate the extracellular GABA concentration and modulate GABAA receptor (GABAAR)-mediated currents. GABA transport inhibitors were applied to study how GABAAR-mediated currents depend on the expression and function of GAT. Nipecotic acid inhibits GABA transport and induced an inward tonic current in concentration-dependent manner during whole cell patch-clamp recordings from SCN neurons. Application of either the selective GABA transporter 1 (GAT1) inhibitors NNC-711 or SKF-89976A, or the GABA transporter 3 (GAT3) inhibitor SNAP-5114, produced only small changes of the baseline current. Coapplication of GAT1 and GAT3 inhibitors induced a significant GABAAR-mediated tonic current that was blocked by gabazine. GAT inhibitors decreased the amplitude and decay time constant and increased the rise time of spontaneous GABAAR-mediated postsynaptic currents. However, inhibition of GAT did not alter the expression of either GAT1 or GAT3 in the hypothalamus. Thus GAT1 and GAT3 functionally complement each other to regulate the extracellular GABA concentration and GABAAR-mediated synaptic and tonic currents in the SCN. Coapplication of SKF-89976A and SNAP-5114 (50 µM each) significantly reduced the circadian period of Per1 expression in the SCN by 1.4 h. Our studies demonstrate that GAT are important regulators of GABAAR-mediated currents and the circadian clock in the SCN. NEW & NOTEWORTHY In the suprachiasmatic nucleus (SCN), the GABA transporters GAT1 and GAT3 are expressed in astrocytes. Inhibition of these GABA transporters increased a tonic GABA current and reduced the circadian period of Per1 expression in SCN neurons. GAT1 and GAT3 showed functional cooperativity: inhibition of one GAT increased the activity but not the expression of the other. Our data demonstrate that GABA transporters are important regulators of GABAA receptor-mediated currents and the circadian clock.

Measurement of continuing charge transfer in rocket-triggered lightning with low-frequency magnetic sensor at close range

2018 ◽  
Vol 175 ◽  
pp. 76-86 ◽  
Author(s):  
Gaopeng Lu ◽  
Yanfeng Fan ◽  
Hongbo Zhang ◽  
Rubin Jiang ◽  
Mingyuan Liu ◽  
...  
Keyword(s):  
Charge Transfer ◽  
Low Frequency ◽  
Magnetic Sensor ◽  
Triggered Lightning ◽  
Close Range

Quantum Dynamics of Exciton Transport and Dissociation in Multichromophoric Systems

2021 ◽  
Vol 72 (1) ◽  
pp. 591-616 ◽  
Author(s):  
Wjatscheslaw Popp ◽  
Dominik Brey ◽  
Robert Binder ◽  
Irene Burghardt
Keyword(s):  
Charge Transfer ◽  
Quantum Dynamics ◽  
Low Frequency ◽  
Functional Materials ◽  
Phonon Modes ◽  
Quantum Dynamical ◽  
Exciton Migration ◽  
Exciton Transport ◽  
Charge Transfer Excitons ◽  
Vibronic Couplings

Due to the subtle interplay of site-to-site electronic couplings, exciton delocalization, nonadiabatic effects, and vibronic couplings, quantum dynamical studies are needed to elucidate the details of ultrafast photoinduced energy and charge transfer events in organic multichromophoric systems. In this vein, we review an approach that combines first-principles parameterized lattice Hamiltonians with accurate quantum dynamical simulations using advanced multiconfigurational methods. Focusing on the elementary transfer steps in organic functional materials, we address coherent exciton migration and creation of charge transfer excitons in homopolymers, notably representative of the poly(3-hexylthiophene) material, as well as exciton dissociation at polymer:fullerene heterojunctions. We emphasize the role of coherent transfer, trapping effects due to high-frequency phonon modes, and thermal activation due to low-frequency soft modes that drive a diffusive dynamics.

G proteins activate ionic conductances at multiple sites in T84 cells

1997 ◽  
Vol 272 (4) ◽  
pp. C1222-C1231
Author(s):  
L. Izu ◽  
M. Li ◽  
R. DeMuro ◽  
M. E. Duffey
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Cell Voltage ◽  
Equilibrium Potential ◽  
T84 Cells ◽  
Ionic Conductances ◽  
Inward Currents ◽  
Cl Channels ◽  
K Current

We examined the role of G proteins in activation of ionic conductances in isolated T84 cells during cholinergic stimulation. When cells were whole cell voltage clamped to the K+ equilibrium potential (E(K)) or Cl- equilibrium potential (E(Cl)) under standard conditions, the cholinergic agonist, carbachol, induced a large oscillating K+ current but only a small inward current. Addition of the GDP analogue, guanosine 5'-O-(2-thiodiphosphate), to pipettes blocked the ability of carbachol to activate the K+ current. Addition of the nonhydrolyzable GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), to pipettes stimulated large oscillating K+ and inward currents. This occurred even when Ca2+ was absent from the bath but not when the Ca2+ chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, was added to pipettes. When all pipette and bath K+ was replaced with Na+ and cells were voltage clamped between E(Na) and E(Cl), GTPgammaS activated oscillating Na+ and Cl- currents. Finally, addition of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to pipettes activated large oscillating K+ currents but only small inward currents. These results suggest that a carbachol-induced release of Ca2+ from intracellular stores is activated by a G protein through the phospholipase C-Ins(1,4,5)P3 signaling pathway. In addition, this or another G protein activates Cl- current by directly gating Cl- channels to increase their sensitivity to Ca2+.

Synaptic Depolarizing GABA Response in Adults Is Excitatory and Proconvulsive When GABAB Receptors Are Blocked

2005 ◽  
Vol 93 (5) ◽  
pp. 2656-2667 ◽  
Author(s):  
Joshua T. Kantrowitz ◽  
N. Noelle Francis ◽  
Alejandro Salah ◽  
Katherine L. Perkins
Keyword(s):  
Voltage Clamp ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Phosphinic Acid ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Gaba Release ◽  
Gabab Receptors ◽  
The Mean ◽  
Ca3 Pyramidal Cells

In the presence of 4-aminopyridine, interneurons fire synchronously, causing giant GABA-mediated postsynaptic potentials (GPSPs; GPSCs in voltage clamp) in CA3 pyramidal cells in hippocampal slices from adult guinea pigs. These triphasic GPSPs are composed of a GABAA-mediated hyperpolarizing component, a depolarizing component, and a GABAB-mediated hyperpolarizing component. We propose that GABAB receptors exert control over the postsynaptic depolarizing GABA response. Microelectrode and cell-attached recordings demonstrated that the mean number of action potentials during the depolarizing component of the GPSP increased dramatically in the presence of the GABAB receptor antagonist (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2- hydroxypropyl](phenylmethyl) phosphinic acid (CGP 55845A; P = 0.003 and 0.0005, respectively). Whole cell voltage-clamp recordings showed that the postsynaptic GABAB and depolarizing GABA components of the GPSC overlap substantially, allowing the GABAB-mediated hyperpolarization to suppress the excitation mediated by the depolarizing GABA component. Further voltage-clamp recordings showed that CGP 55845A increased the duration of the depolarizing GABA component of the GPSC even when the GABAB component had already been blocked by internal QX-314, suggesting that CGP 55845A also increased the duration of GABA release. When glutamatergic transmission is intact, GPSPs directly precede epileptiform afterdischarges. We hypothesize that the depolarizing component of the GPSP triggers the epileptiform events and show here that enhancement of the depolarizing component with CGP 55845A increased epileptiform activity. CGP 55845A increased the likelihood of a GPSP triggering an epileptiform event from 32 to 99% ( P = 0.0000001), and significantly increased the number of afterdischarges per epileptiform event ( P = 0.001). Loss of GABAB receptor function is associated with temporal lobe epilepsy in rodents and humans. We show here that GABAB receptors exert control over the synaptic depolarizing GABA response and that block of GABAB receptors makes the depolarizing GABA response excitatory and proconvulsive.

scholarly journals 5-HT1B Receptor-Mediated Presynaptic Inhibition of GABA Release in the Suprachiasmatic Nucleus

2005 ◽  
Vol 93 (6) ◽  
pp. 3157-3164 ◽  
Author(s):  
Jayne R. Bramley ◽  
Patricia J. Sollars ◽  
Gary E. Pickard ◽  
F. Edward Dudek
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Receptor Agonist ◽  
Gaba Release ◽  
Presynaptic Receptors ◽  
Clear Effect ◽  
Whole Cell Patch Clamp ◽  
Bath Application ◽  
Hypothalamic Slices ◽  
Photic Input ◽  
Serotonergic Innervation

The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT1B) presynaptic receptors on retinal glutamatergic terminals. However, the majority of 5-HT1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT1B receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT1B receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat and mouse SCN neurons in hypothalamic slices. Using CsCl-containing microelectrodes with QX314, we isolated mPSCs that were sensitive to the GABAA receptor antagonist, bicuculline. Bath application of CP-93,129 (1 μM) decreased the frequency of mIPSCs by an average of 22% ( n = 7) in rat SCN neurons and by an average of 30% ( n = 8) in mouse SCN neurons with no clear effect on mIPSC amplitude. In mice lacking functional 5-HT1B receptors, CP-93,129 (1 μM) had no clear effect on the frequency or the amplitude of mIPSCs recorded in any of the cells tested ( n = 4). The decrease in the frequency of mIPSCs of SCN neurons produced by the selective 5-HT1B receptor agonist CP-93,129 is consistent with the interpretation that 5-HT1B receptors are located on GABA terminals in the SCN and that 5-HT inhibits GABA release via a 5-HT1B presynaptic receptor-mediated mechanism.

Model Passivated Carbon Electrodes for Fluorine Generation in MSRs and the Nuclear Fuel Cycle

2013 ◽  
Author(s):  
Kelvin S.-H. Seto ◽  
Brian M. Ikeda
Keyword(s):  
Charge Transfer ◽  
Molten Salt ◽  
Nuclear Fuel ◽  
Fuel Cycle ◽  
Nuclear Fuel Cycle ◽  
Chemical System ◽  
Equilibrium Potential ◽  
Carbon Electrodes ◽  
Test Model ◽  
F2 Generation

Elemental fluorine, F2, is used in the nuclear fuel cycle for the isotopic separation of uranium-235 and 238, as well as for the purification of LiF-BeF2 in molten salt reactors. F2 is generated on an industrial scale by an electrochemical process using carbon electrodes in a KF-2HF molten salt. Carbon electrodes are used for industrial F2 generation due to its chemical stability, high conductivity, and relatively low cost. One of the main issues faced when using carbon electrodes in this chemical system is passivation through the formation of C-F compounds on the surface of the electrode. This results in a loss of anode wettability to the electrolyte and diminished charge transfer rate. The voltage needed for the fluorine evolution reaction increases which negatively impacts the safety of the system, increases the operating costs, and leads to faster degradation of the electrode. The degradation of electrical properties during passivation is progressive, eventually leading to electrode deactivation. The process of deactivation begins with a passivating C-F layer at potentials above the equilibrium potential (2.92 V). The layer is both non-wetting to the KF-2HF media and insulating. Deactivation begins with inhibited F2 bubble detachment, formation of a persistent gas layer, and finally deactivation as the electrode surface is completely covered by a thick, insulating C-F layer causing charge transfer to cease. Only a small current is able to flow, even at high potentials (up to 9 V), indicating F2 generation is completely inhibited. The purpose of this study is to manufacture and test model carbon electrodes and, to examine the non-wetting properties of a partially fluorinated surface. The electrodes will be prepared by mixing PTFE-particles with Vulcan carbon powder and then pressing to form pellets. These electrodes should have a reproducible surface for electrochemical performance studies that will lead to a better understanding of the surface chemistry. The research will develop novel electrodes with a goal to minimize the voltage required for F2 production. This will enhance the efficiency in the overall process and lower the manufacturing costs for F2. Carbon electrodes with different PTFE-content (20 w.% and 35 w.%) were synthesized. Electrochemical fluorination was then carried out at different potentials in the F2 generation region (4 to 8 V) in molten KF·2HF electrolyte at ∼90 °C. The electrochemical behaviour of the carbon-PTFE electrodes was examined and compared for both fluorine passivated and non-passivated graphite, amorphous carbon, and vitreous carbon electrodes. The growth of the electrical double-layer capacitance between the carbon electrodes and the KF·2HF molten salt was studied. The effects of composition of fluorinated and non-fluorinated carbon on electrode performance are presented.

Allosteric modulation of GABAA receptors in acutely dissociated neurons of the suprachiasmatic nucleus

1996 ◽  
Vol 270 (6) ◽  
pp. C1726-C1734 ◽  
Author(s):  
M. Shimura ◽  
N. Harata ◽  
M. Tamai ◽  
N. Akaike
Keyword(s):  
Gabaa Receptor ◽  
Suprachiasmatic Nucleus ◽  
Gabaa Receptors ◽  
Response Curve ◽  
Equilibrium Potential ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Gabaa Receptor Antagonist ◽  
Inward Currents ◽  
Concentration Response Curve

The gamma-aminobutyric acid (GABA)-induced response was investigated in acutely dissociated suprachiasmatic nucleus (SCN) neurons of 11- to 14-day-old rats, under the voltage-clamp condition of nystatin-perforated patch recording. At a holding potential of -40 mV, application of GABA induced inward currents in a concentration-dependent manner. Pentobarbital and 5 beta-pregnan-3 alpha-ol-20-one (pregnanolone) similarly induced inward currents. GABA-induced inward currents were suppressed in a concentration-dependent manner by pretreating neurons with a GABAA receptor antagonist, bicuculline. Bicuculline (3 x 10(-6) M) shifted the concentration-response curve of GABA to the left in a competitive manner. Reversal potential of the GABA response (EGABA) was -3.4 +/- 0.7 mV, close to the theoretical Cl- equilibrium potential of -4.1 mV. Pretreating SCN neurons with diazepam, pentobarbital, and pregnanolone enhanced the 3 x 10(-6) M GABA response. Diazepam (3 x 10(-8) M), pentobarbital (3 x 10(-5) M), and pregnanolone (10(-7) M) shifted the concentration-response curve of GABA to the left without changing the maximal amplitude of GABA responses. EGABA in the presence of diazepam, pentobarbital, or pregnanolone was the same as that in their absence. These results show that the GABA response in acutely dissociated SCN neurons is mediated by the GABAA receptor. Because the GABAA receptor of SCN neurons is allosterically augmented by diazepam, pentobarbital, and pregnanolone, similarly as in other regions of the central nervous system, the present study opens up ways to functionally modulate the GABAA receptors in SCN.

scholarly journals Vibronic coherence evolution in multidimensional ultrafast photochemical processes

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
James D. Gaynor ◽  
Jason Sandwisch ◽  
Munira Khalil
Keyword(s):  
Excited State ◽  
Charge Transfer ◽  
Vibrational Spectroscopy ◽  
Low Frequency ◽  
Coherence Transfer ◽  
Transfer Energy ◽  
Electronic Delocalization ◽  
Vibronic States ◽  
High Frequency Vibrations ◽  
Vibronic Couplings

AbstractThe complex choreography of electronic, vibrational, and vibronic couplings used by photoexcited molecules to transfer energy efficiently is remarkable, but an unambiguous description of the temporally evolving vibronic states governing these processes has proven experimentally elusive. We use multidimensional electronic-vibrational spectroscopy to identify specific time-dependent excited state vibronic couplings involving multiple electronic states, high-frequency vibrations, and low-frequency vibrations which participate in ultrafast intersystem crossing and subsequent relaxation of a photoexcited transition metal complex. We discover an excited state vibronic mechanism driving long-lived charge separation consisting of an initial electronically-localized vibrational wavepacket which triggers delocalization onto two charge transfer states after propagating for ~600 femtoseconds. Electronic delocalization consequently occurs through nonadiabatic internal conversion driven by a 50 cm−1 coupling resulting in vibronic coherence transfer lasting for ~1 picosecond. This study showcases the power of multidimensional electronic-vibrational spectroscopy to elucidate complex, non-equilibrium energy and charge transfer mechanisms involving multiple molecular coordinates.

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