In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis

Lerma, Juan; Herranz, Arantxa; Herreras, Óscar; Abraira, Víctor; Rı́o, Rafael Martı́n del

doi:10.1016/0006-8993(86)91230-8

Cited by 391 publications

(256 citation statements)

References 22 publications

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“…We also suggest that, because in all likelihood the concentration of ambient GABA in our slices under control conditions is lower than that which exists in vivo (Lerma et al, 1986), our apparent tonic current amplitude in vitro may be an underestimation of its in vivo counterpart. Furthermore, given that the concentration of ambient GABA in vivo is likely to depend on the activity of GABA-releasing neurons, we might expect that tonic current amplitude would dynamically fluctuate.…”

Section: Properties Of the Tonic Gaba A Currentmentioning

confidence: 71%

GABA_AReceptor-Mediated Tonic Inhibition in Thalamic Neurons

Cope

Hughes²,

Crunelli³

2005

J. Neurosci.

284

342

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Tonic GABA A receptor-mediated inhibition is typically generated by ␦ subunit-containing extrasynaptic receptors. Because the ␦ subunit is highly expressed in the thalamus, we tested whether thalamocortical (TC) neurons of the dorsal lateral geniculate nucleus (dLGN) and ventrobasal complex exhibit tonic inhibition. Focal application of gabazine (GBZ) (50 M) revealed the presence of a 20 pA tonic current in 75 and 63% of TC neurons from both nuclei, respectively. No tonic current was observed in GABAergic neurons of the nucleus reticularis thalami (NRT). Bath application of 1 M GABA increased tonic current amplitude to ϳ70 pA in 100% of TC neurons, but it was still not observed in NRT neurons. In dLGN TC neurons, the tonic current was sensitive to low concentrations of the ␦ subunit-specific receptor agonists allotetrahydrodeoxycorticosterone (100 nM) and 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) (100 nM) but insensitive to the benzodiazepine flurazepam (5 M). Bath application of low concentrations of GBZ (25-200 nM) preferentially blocked the tonic current, whereas phasic synaptic inhibition was primarily maintained. Under intracellular current-clamp conditions, the preferential block of the tonic current with GBZ led to a small depolarization and increase in input resistance. Using extracellular single-unit recordings, block of the tonic current caused the cessation of low-threshold burst firing and promoted tonic firing. Enhancement of the tonic current by THIP hyperpolarized TC neurons and promoted burst firing. Thus, tonic current in TC neurons generates an inhibitory tone. Its modulation contributes to the shift between different firing modes, promotes the transition between different behavioral states, and predisposes to absence seizures.

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Section: Properties Of the Tonic Gaba A Currentmentioning

confidence: 71%

GABA_AReceptor-Mediated Tonic Inhibition in Thalamic Neurons

Cope

Hughes²,

Crunelli³

2005

J. Neurosci.

284

342

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“…Additional factors such as anatomical barriers to diffusion as seen in the cerebellar glomerulus can influence levels of ambient GABA (Rossi and Hamann, 1998) as can alterations in the metabolic clearance rate via GABA transaminase (Overstreet and Westbrook, 2001). In fact, ambient levels of GABA appear to be closely controlled by these mechanisms to achieve mean levels close to 0.8-3 μM in the extracellular space (Lerma et al, 1986;Wu et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Short-term steroid treatment increases δ GABAA receptor subunit expression in rat CA1 hippocampus: Pharmacological and behavioral effects

et al. 2005

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In this study, 48 h administration of 3α-OH-5β-pregnan-20-one (3α,5β-THP) or 17β-estradiol (E 2 )+progesterone (P) to female rats increased expression of the δ subunit of the GABA A receptor (GABAR) in CA1 hippocampus. Coexpression of α4 and δ subunits was suggested by an increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), following 48 h steroid treatment, and nearly complete blockade by 300 μM lanthanum (La 3+ ). Because α4βδ GABAR are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice. The La 3+ -sensitive THIP current, representative of current gated by α4βδ GABAR, was measurable only following 48 h steroid treatment. In contrast, the bicucullinesensitive current was not altered by steroid treatment, assessed with or without 200 nM gabazine to block synaptic current. However, 48 h steroid treatment resulted in a tonic current insensitive to the benzodiazepine agonists lorazepam (10 μM) and zolpidem (100 nM). These results suggest that 48 h steroid treatment increases expression of α4βδ GABAR which replace the ambient receptor population. Increased anxiolytic effects of THIP were also observed following 48 h steroid treatment. The findings from the present study may be relevant for alterations in mood and benzodiazepine sensitivity reported across the menstrual cycle.

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“…After a 1-hr recovery period, slices were placed in a laminar flow recording chamber and superfused with amedium containing (in mM) 125 NaCl, 5 KCI, 4 MgCl2, 4 CaCl2, 26 NaHCO3, 1 NaH2PO4, and 10 glucose and equilibrated with 95% 02/5% CO2. For all experiments examining synaptic currents or iontophoretic responses in slices, picrotoxin (50-100 lOM) and DL-2-amino-5-phosphonovaleric acid (50 ,uM) were added to the medium to block y-aminobutyric acid type A (GABAA) receptors and NMDA receptors, respectively.…”

Section: Methodsmentioning

confidence: 99%

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

Isaacson

Nicoll²

1991

Proc. Natl. Acad. Sci. U.S.A.

184

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Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544]. We have used patch clamp recording techniques in hippocampal slices to elucidate the mechanism for this selective action. We find that aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization. In addition, aniracetam selectively prolongs the time course and increases the peak amplitude of fast synaptic currents. A general property of neurotransmitter receptor channels is that in the cQntinuous presence of agonist the response rapidly diminishes. Although this desensitization, which results from a conformational change in the receptors, is readily demonstrated for a number of neurotransmitters, including acetylcholine (1, 2), y-aminobutyric acid (3), glycine (4), serotonin (5), and glutamate (6-12), a physiological role for desensitization in synaptic transmission has not been established. Rapid perfusion experiments with the non-N-methyl-D-aspartate (NMDA) type of glutamate receptor indicate that this receptor desensitizes extremely quickly in the presence of glutamate (6,7,(10)(11)(12) with a time course similar to that of glutamate-mediated synaptic responses. We have investigated whether desensitization could contribute to the decay of excitatory postsynaptic currents (EPSCs) (6, 7). We find that aniracetam, a drug reported to enhance glutamate responses (13), strongly reduces glutamate receptor desensitization. In addition, this drug prolongs the time course and increases the peak amplitude of synaptic currents. These findings suggest that receptor desensitization governs the strength of excitatory synaptic transmission in the brain. MATERIALS AND METHODSExperiments were performed on guinea pig hippocampal slices (500 jmm) prepared by standard methods (14). After a 1-hr recovery period, slices were placed in a laminar flow recording chamber and superfused with amedium containing (in mM) 125 NaCl, 5 KCI, 4 MgCl2, 4 CaCl2, 26 NaHCO3, 1 NaH2PO4, and 10 glucose and equilibrated with 95% 02/5% CO2. For all experiments examining synaptic currents or iontophoretic responses in slices, picrotoxin (50-100 lOM) and DL-2-amino-5-phosphonovaleric acid (50 ,uM) were added to the medium to block y-aminobutyric acid type A (GABAA) receptors and NMDA receptors, respectively. In the majority of experiments examining iontophoretic responses, tetrodotoxin (0.5-1 1uM) was included to block sodium-dependent action potentials. Currents were recorded with an Axopatch 1B amplifier from neurons in the CA1 and CA3 pyramidal cell layers and granule cell layer of the dentate gyrus using the "blind" whole-cell recording technique (15,16 NaCI, pH 8). All experiments were performed at room temperature at a holding potential of -80 mV, unless otherwise state...

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In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis

Cited by 391 publications

References 22 publications

GABA_AReceptor-Mediated Tonic Inhibition in Thalamic Neurons

GABA_AReceptor-Mediated Tonic Inhibition in Thalamic Neurons

Short-term steroid treatment increases δ GABAA receptor subunit expression in rat CA1 hippocampus: Pharmacological and behavioral effects

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

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In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis

Cited by 391 publications

References 22 publications

GABAAReceptor-Mediated Tonic Inhibition in Thalamic Neurons

GABAAReceptor-Mediated Tonic Inhibition in Thalamic Neurons

Short-term steroid treatment increases δ GABAA receptor subunit expression in rat CA1 hippocampus: Pharmacological and behavioral effects

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

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GABA_AReceptor-Mediated Tonic Inhibition in Thalamic Neurons

GABA_AReceptor-Mediated Tonic Inhibition in Thalamic Neurons