Cited by 522Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionIon channel regulation and function

Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor‐mediated responses in neocortex of rat and cat.

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Connors, B W, Malenka, R C, Silva, L R·1988·The Journal of Physiology

Abstract

1. Pyramidal neurones from layers II and III of the rat primary somatosensory cortex and cat primary visual cortex were studied in vitro. Inhibitory postsynaptic potentials (IPSPs) and responses to exogenously applied gamma-aminobutyric acid (GABA) and its analogue baclofen were characterized. The results from rats and cats were very similar. 2. Single electrical stimuli to deep cortical layers evoked a sequence of PSPs in the resting neurone: (a) an initial, brief excitation (EPSP), (b) a short-latency, fast inhibition (the f-IPSP) and (c) a long-latency, more prolonged inhibition (the l-IPSP). The f-IPSP was accompanied by a large conductance increase (about 70-90 nS) and reversed polarity at -75 mV; the l-IPSP displayed a relatively small conductance increase (about 10-20 nS) and reversed at greater than -90 mV. 3. Focal application of GABA near the soma evoked a triphasic response when measured near the threshold voltage for action potentials: (a) the GABAhf (hyperpolarizing, fast) phase was very brief and was generated by a large conductance increase with a reversal potential of -78 mV, (b) the GABAd (depolarizing) phase also had a high conductance but reversed at -51 mV, (c) the GABAhl (hyperpolarizing, long-lasting) phase had a relatively low conductance and reversed at -70 mV. The GABAhf response was specifically localized to the soma, whereas the apical or basilar dendrites generated predominantly GABAd responses. 4. Baclofen, a selective GABAB receptor agonist, caused a small (about 2 mV), slow hyperpolarization of the resting potential, which reversed at -90 mV. Saturating baclofen doses increased membrane conductance by a maximum of about 12 nS. Baclofen depressed the amplitude and conductance of PSPs; when baclofen was focally applied near the soma. IPSPs were selectively depressed. 5. The GABAA receptor antagonists bicuculline methiodide or picrotoxin (10 microM) greatly depressed f-IPSPs, but either enhanced or did not affect l-IPSPs. Concomitantly, GABAhf and GABAd responses were antagonized, leaving a more prominent GABAhl response that reversed polarity at a more negative level of -87 mV. Baclofen responses were unaffected by bicuculline and picrotoxin. Extracellular barium abolished the baclofen response, and shifted the reversal potentials of the GABAd and GABAhl responses in the positive direction; the GABAhf response was unaffected. 6. Both focal GABA and f-IPSPs strongly depressed the intrinsic excitability of pyramidal neurones. Each greatly increased spike threshold and abolished or vastly reduced the capacity of the cells to fire repetitively during intense stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

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  • GABAergic agonists like benzodiazepines impair LTP and LTP-related plasticity in glutamatergic synapses via activation of GABA A receptor.

    “GABAergic agonists, like benzodiazepines that are also used clinically to improve sleep, were consistently revealed to impair LTP as well as LTP-related plasticity in glutamatergic synapses via activation of the ionotropic GABA A receptor (e.g., Refs. 225, 277, 549, 575, 633, 1008Refs. 225, 277, 549, 575, 633, , 1270)).”

    From About Sleep's Role in Memory (2013) · cites this paper as [225]

    The study summary (page not supplied) reports GABAA receptor-mediated inhibitory responses and reduced excitability of rat and cat cortical neurons after GABA application. It does not report that benzodiazepines impair LTP or LTP-related plasticity at glutamatergic synapses; the GABA analogue it tests, baclofen, is identified as a GABAB agonist. (LLM, conf=0.84)

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References 48 · Cited by 522

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Authors
Connors, B. W., Malenka, R. C., & Silva, L. R.
Affiliations
Stanford Medicine (US)
Venue
The Journal of Physiology
Publisher
Wiley
Published
1988-12
Volume
406
Issue
1
Pages
443-468
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
OpenAlex
W1969319931
Cited by
522
References
48
Citations by year
2026: 3 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 9 · 2014: 15 · 2013: 9 · 2012: 12
FWCI
6.34
Type
journal article
Language
en
Open access
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS 01016, NS12151)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
inhibitory postsynaptic potentials, GABAA receptor, GABAB receptors, baclofen, pyramidal neurons, primary somatosensory cortex, primary visual cortex, membrane conductance, bicuculline methiodide, picrotoxin, synaptic depression, rats, cats, comparative neurophysiology
MeSH terms
Action Potentials, Animals, Baclofen, Barium, Bicuculline, Cats, gamma-Aminobutyric Acid, Neural Inhibition, Neurons, Picrotoxin, Receptors, GABA-A, Somatosensory Cortex, Synapses, Time Factors, Visual Cortex, Rats, In Vitro Techniques

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