Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat.
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)
Connors
B W
BW
Department of Neurology, Stanford University School of Medicine, CA 94305.
Malenka
R C
RC
Silva
L R
LR
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002415:Cats; D066298:In Vitro Techniques; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D013003:Somatosensory Cortex / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D014793:Visual Cortex / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001418:Baclofen; D001464:Barium; D001640:Bicuculline; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid