title: Differential arithmetic of shunting inhibition for voltage and spike rate in neocortical pyramidal cells.
abstract: The main inhibitory neurotransmitter in the mammalian forebrain is gamma-amino butyric acid (GABA), which acts through A and B type receptors. GABAA receptors mediate inhibition via an increase in membrane conductance (shunting) and/or membrane potential hyperpolarization. Shunting inhibition is thought to decrease the gain between neural input and output, and thus to act as a divisor, but may do so only below the spike threshold. To investigate the role of shunting inhibition in neocortical neurons, whole-cell patch-clamp recordings were obtained from layer V pyramidal cells of somatosensory cortex in juvenile rats. Sub- and suprathreshold voltage responses were elicited by somatic step current injections and a shunting conductance was generated via a dynamic clamp. Increasing the dynamic clamp shunting conductance led to a parallel shift of the current-discharge curves and a reduced slope of the current-voltage relationship, i.e. a decrease of neural gain. Selective activation of GABAAA receptors with the competitive agonist isoguvacine or rises of endogenous GABA with the specific reuptake blocker nipecotic acid led to a proportional decrease of subthreshold membrane voltage, but a constant offset of discharge rates, thus acting like a shunting conductance. Similarly, isoguvacine and nipecotic acid decreased the gain of excitatory postsynaptic potentials. In all three experimental conditions, shunting inhibition divisively affected subthreshold voltages, while the time-averaged suprathreshold membrane potential was offset by a constant amount. I conclude that shunting inhibition in pyramidal cells has a dual impact on neural output: it is divisive for subthreshold voltages but subtractive for spike frequencies.
authors: Institute of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland. ulrich@pyl.unibe.ch
authors: Daniel
authors: D
authors: Ulrich
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004056:Differential Threshold / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007539:Isonicotinic Acids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019579:Neocortex / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D018756:GABA Antagonists; D007539:Isonicotinic Acids; D009557:Nipecotic Acids; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C030278:nipecotic acid; C015300:isoguvacine