scholarly journals Reduced GABAB receptor subunit expression and paired-pulse depression in a genetic model of absence seizures

2007 ◽  
Vol 25 (3) ◽  
pp. 631-641 ◽  
Author(s):  
D. Merlo ◽  
C. Mollinari ◽  
Y. Inaba ◽  
A. Cardinale ◽  
A.M. Rinaldi ◽  
...  
Keyword(s):  
Genetic Model ◽  
Gabab Receptor ◽  
Receptor Subunit ◽  
Absence Seizures ◽  
Paired Pulse ◽  
Subunit Expression ◽  
Paired Pulse Depression

scholarly journals Ontogenesis of Presynaptic GABAB Receptor-Mediated Inhibition in the CA3 Region of the Rat Hippocampus

1998 ◽  
Vol 79 (3) ◽  
pp. 1341-1348 ◽  
Author(s):  
Olivier Caillard ◽  
Heather A. McLean ◽  
Yehezkel Ben-Ari ◽  
Jean-Luc Gaïarsa
Keyword(s):  
Pyramidal Neurons ◽  
Gabab Receptor ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Rat Hippocampus ◽  
Dependent Manner ◽  
Paired Pulse ◽  
Ca3 Pyramidal Neurons ◽  
Paired Pulse Depression ◽  
Ca3 Region

Caillard, Olivier, Heather A. McLean, Yehezkel Ben-Ari, and Jean-Luc Gaı̈arsa. Ontogenesis of presynaptic GABAB receptor-mediated inhibition in the CA3 region of the rat hippocampus. J. Neurophysiol. 79: 1341–1348, 1998. γ-Aminobutyric acid-B(GABAB) receptor-dependent and -independent components of paired-pulse depression (PPD) were investigated in the rat CA3 hippocampal region. Intracellular and whole cell recordings of CA3 pyramidal neurons were performed on hippocampal slices obtained from neonatal (5–7 day old) and adult (27–34 day old) rats. Electrical stimulation in the hilus evoked monosynaptic GABAA postsynaptic currents (eIPSCs) isolated in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and d(−)2-amino-5-phosphovaleric acid (d-AP5, 50 μM) with 2(triethylamino)- N-(2,6-dimethylphenyl) acetamine (QX314) filled electrodes. In adult CA3 pyramidal neurons, when a pair of identical stimuli was applied at interstimulus intervals (ISIs) ranging from 50 to 1,500 ms the amplitude of the second eIPSC was depressed when compared with the first eIPSC. This paired-pulse depression (PPD) was partially blockedb y  P - 3 - a m i n o p r o p y l - P - d i e t h o x y m e t h y l  p h o s p h o r i c  a c i d(CGP35348, 0.5 mM), a selective GABAB receptor antagonist. In neonates, PPD was restricted to ISIs shorter than 200 ms and was not affected by CGP35348. The GABAB receptor agonist baclofen reduced the amplitude of eIPSCs in a dose-dependent manner with the same efficiency in both adults and neonates. Increasing the probability of transmitter release with high Ca2+ (4 mM)/low Mg2+ (0.3 mM) external solution revealed PPD in neonatal CA3 pyramidal neurons that was 1) partially prevented by CGP35348, 2) independent of the membrane holding potential of the recorded cell, and 3) not resulting from a change in the reversal potential of GABAA eIPSCs. In adults the GABA uptake blocker tiagabine (20 μM) increased the duration of eIPSCs and the magnitude of GABAB receptor-dependent PPD. In neonates, tiagabine also increased duration of eIPSCs but to a lesser extent than in adult and did not reveal a GABAB receptor-dependent PPD. These results demonstrate that although GABAB receptor-dependent and -independent mechanisms of presynaptic inhibition are present onGABAergic terminals and functional, they do not operate at the level of monosynaptic GABAergic synaptic transmission at early stages of development. Absence of presynaptic autoinhibition of GABA release seems to be due to the small amount of transmitter that can access presynaptic regulatory sites.

Discrimination of post- and presynaptic GABAB receptor-mediated responses by tetrahydroaminoacridine in area CA3 of the rat hippocampus

1993 ◽  
Vol 69 (2) ◽  
pp. 630-635 ◽  
Author(s):  
N. A. Lambert ◽  
W. A. Wilson
Keyword(s):  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Hippocampal Slices ◽  
Outward Current ◽  
Gabab Receptors ◽  
Rat Hippocampus ◽  
Stratum Radiatum ◽  
Paired Pulse ◽  
Paired Pulse Depression ◽  
Area Ca3

1. The effects of the K+ channel blocker 9-amino-1,2,3,4-tetrahydroacridine (THA) on the actions of baclofen and gamma-aminobutyric acid (GABA) at post- and presynaptic GABAB receptors were studied with whole-cell voltage-clamp recording in area CA3 of rat hippocampal slices. 2. The effect of THA on postsynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with potassium gluconate and guanosine triphosphate (GTP). At a holding potential of -70 mV, the GABAB receptor agonist (+/-)-baclofen (30 microM) induced an outward current and increased membrane conductance. In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovalerate (APV), stimulation in stratum pyramidale or proximal stratum radiatum evoked GABAA receptor-mediated, fast monosynaptic inhibitory postsynaptic currents (IPSCs) and GABAB receptor-mediated, late monosynaptic IPSCs. THA (0.3 mM) blocked the baclofen-induced current and conductance increase and GABAB receptor-mediated IPSCs. 3. The effect of THA on presynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with Cs+ and lidocaine N-ethyl bromide (QX-314), which blocked post-synaptic GABAB receptor-mediated responses. Stimulation in the presence of DNQX and APV evoked GABAA receptor-mediated IPSCs; when pairs of stimuli were delivered 200 ms apart the second IPSC was depressed. Baclofen reversibly depressed IPSCs, and partially occluded paired-pulse depression of IPSCs. The GABAB receptor antagonist CGP 35348 (0.5-1.0 mM) reversed baclofen-induced depression of IPSCs and partially blocked paired-pulse depression. Baclofen-induced and paired-pulse depression of IPSCs were not by affected by THA (0.3 mM). 4. Baclofen reversibly decreased the amplitude and frequency of spontaneous monosynaptic IPSCs (sIPSCs). Depression of sIPSCs by baclofen was unchanged by THA. 5. These results indicate that THA blocks the actions of baclofen and GABA at post- but not presynaptic GABAB receptors. We conclude that post- and presynaptic GABAB receptors in area CA3 of the rat hippocampus couple to different effector mechanisms; postsynaptic GABAB receptors activate THA-sensitive K+ channels, and presynaptic GABAB receptors decrease neurotransmitter release through a THA-insensitive mechanism.

Ontogeny of GABAB receptor subunit expression and function in the rat spinal cord

2003 ◽  
Vol 972 (1-2) ◽  
pp. 197-206 ◽  
Author(s):  
Scott A. Sands ◽  
Maya Gadhvi Purisai ◽  
Bibie M. Chronwall ◽  
S.J. Enna
Keyword(s):  
Spinal Cord ◽  
Gabab Receptor ◽  
Receptor Subunit ◽  
Rat Spinal Cord ◽  
Subunit Expression ◽  
And Function

GABAB autoreceptors mediate activity-dependent disinhibition and enhance signal transmission in the dentate gyrus

1993 ◽  
Vol 69 (3) ◽  
pp. 674-691 ◽  
Author(s):  
D. D. Mott ◽  
C. W. Xie ◽  
W. A. Wilson ◽  
H. S. Swartzwelder ◽  
D. V. Lewis
Keyword(s):  
Dentate Gyrus ◽  
Receptor Antagonist ◽  
Granule Cells ◽  
Gabab Receptor ◽  
Mossy Fiber ◽  
Signal Transmission ◽  
Paired Pulse ◽  
Activity Dependent ◽  
Paired Pulse Depression ◽  
Stimulation Of

1. Activity-dependent depression (fading) of polysynaptic inhibition and the effects of this disinhibition on signal transmission were studied in the dentate gyrus of the rat hippocampal slice with the use of intracellular and extracellular recordings. 2. Polysynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) were evoked in dentate granule cells by stimulation of mossy fibers in stratum lucidum of area CA3b/c. These mossy fiber-evoked IPSP/Cs consisted of an early GABAA receptor-mediated component (IPSP/CA) and a late GABAB receptor-mediated component (IPSP/CB). 3. When paired stimuli were delivered 200 ms apart under voltage clamp, the amplitude of the IPSCA and IPSCB evoked by the second stimulus was reduced by 37.0 +/- 4.0 and 61.6 +/- 7.8% (mean +/- SE), respectively. Paired-pulse depression of both IPSCA and IPSCB was greatest at interstimulus intervals of 100-400 ms with a maximal effect when stimuli were delivered 200 ms apart. 4. (+/-) Baclofen, a GABAB receptor agonist, suppressed both components of the mossy fiber-evoked IPSP in a concentration-dependent fashion. At a concentration that only partially suppressed the initial IPSP, baclofen occluded paired-pulse depression of IPSPA. In addition, paired-pulse depression of IPSPA was blocked in a concentration-dependent fashion by 2-hydroxy-saclofen (10-400 microM), a GABAB receptor antagonist. 5. The contribution of the IPSPB conductance increase to paired-pulse depression of IPSPA was evaluated. Paired-pulse depression of IPSPA was significantly greater than was the depression of the response to a current pulse delivered 200 ms after the mossy fiber stimulus. In addition, injection of granule cells with GTP gamma S, a nonhydrolyzable guanosine triphosphate (GTP) analogue, occluded both IPSPB as well as the effects of baclofen on the granule cell membrane by activating G proteins but did not reduce paired-pulse depression of IPSPA or suppression of IPSPA by baclofen. Finally, examination of the first and second IPSCA evoked by paired stimuli 200 ms apart revealed no significant differences in response kinetics. Taken together, these results indicate that postsynaptic GABAB receptors on the granule cells are not responsible for paired-pulse depression of IPSPA. 6. Monosynaptic IPSPs were evoked by direct stimulation of inhibitory neurons in the inner molecular layer of the dentate gyrus during pharmacological blockade of excitatory transmission with D(-)-2-amino-5-phosphonovaleric acid (D-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA glutamate receptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

Hippocampal CA1 lacunosum-moleculare interneurons: modulation of monosynaptic GABAergic IPSCs by presynaptic GABAB receptors

1995 ◽  
Vol 74 (5) ◽  
pp. 2126-2137 ◽  
Author(s):  
R. Khazipov ◽  
P. Congar ◽  
Y. Ben-Ari
Keyword(s):  
Receptor Antagonist ◽  
Transmitter Release ◽  
Gabab Receptor ◽  
Molecular Layer ◽  
Pyramidal Cells ◽  
Gabab Receptors ◽  
Stratum Radiatum ◽  
Paired Pulse ◽  
High Level ◽  
Paired Pulse Depression

1. Whole cell patch-clamp recordings were employed to characterize monosynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stratum lacunosum moleculare, or near the border of the stratum radiatum (LM interneurons), in the CA1 region of hippocampal slices taken from 3- to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM) were biphasic. The gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (20 microM), blocked the fast IPSC, and the slow IPSC was blocked by the GABAB receptor antagonist CGP35348 (500 microM). 2. Monosynaptic IPSCs were evoked by electrical stimulation in several distant regions including the stratum radiatum, the stratum oriens, the stratum lacunosum-moleculare, and the molecular layer of dentate gyrus, suggesting an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs were evoked by electrical stimulation of most of these distal regions with the exception of the molecular layer of dentate gyrus, which evoked an IPSC only in LM interneurons. 3. Frequent (> 0.1 Hz) stimulation depressed the evoked IPSCs. With a paired-pulse protocol, the second IPSC was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms. 4. The GABAB receptor agonist baclofen (1 microM) reduced the amplitude of evoked IPSCs and the paired-pulse depression of the second IPSC. The GABAB receptor antagonist CGP35348 (0.5-1 mM) had no significant effect on the amplitude of isolated IPSCs. However, CGP35348 reduced but did not fully block paired-pulse depression, suggesting that this depression is partly due to the activation of presynaptic GABAB receptors. 5. The paired-pulse depression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concentration to 4 mM and reducing the extracellular Mg2+ concentration to 0.1 mM, enhanced the depression. Reduction of transmitter release by increasing extracellular Mg2+ concentration to 7 mM diminished the paired-pulse depression of IPSCs. After potentiation of transmitter release, CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesium medium was preferentially due to the potentiation of a GABAB-independent component. 6. In summary, monosynaptic IPSCs recorded in LM interneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and the degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.

GABAB receptor subunit expression in glia

2003 ◽  
Vol 24 (1) ◽  
pp. 214-223 ◽  
Author(s):  
K.J Charles ◽  
J Deuchars ◽  
C.H Davies ◽  
M.N Pangalos
Keyword(s):  
Gabab Receptor ◽  
Receptor Subunit ◽  
Subunit Expression
Sign in / Sign up

Export Citation Format

Share Document