Outwardly rectifying tonically active GABAA receptors in pyramidal cells modulate neuronal offset, not gain.
Hippocampal pyramidal cell excitability is regulated both by fast synaptic inhibition and by tonically active high-affinity extrasynaptic GABA(A) receptors. The impact of tonic inhibition on neuronal gain and offset, and thus on information processing, is unclear. Offset is altered by shunting inhibition, and the gain of a neuronal response to an excitatory input can be modified by changing the level of "background" synaptic noise. Therefore, tonic activation of GABA(A) receptors would be expected to modulate offset and, in addition, to alter gain through a shunting effect on synaptic noise. Here we show that tonically active GABA(A) receptors in CA1 pyramidal cells show marked outward rectification, while the peaks of IPSCs exhibit a linear current-voltage relationship. As a result, tonic GABA(A) receptor-mediated currents have a minimal effect upon subthreshold membrane potential variation due to synaptic noise, but predominantly affect neurons at spiking threshold. Consistent with this, tonic GABA(A) receptor-mediated currents in pyramidal cells exclusively affect offset and not gain. Modulation of tonically active GABA(A) receptors by fluctuations in extracellular GABA concentrations or neuromodulators acting on high-affinity receptors potentially provides a powerful mechanism to alter neuronal offset independently of neuronal gain.
Pavlov
Ivan
I
UCL Institute of Neurology, University College London, London WC1 N3BG, United Kingdom.
Savtchenko
Leonid P
LP
Kullmann
Dimitri M
DM
Semyanov
Alexey
A
Walker
Matthew C
MC
D000818:Animals; D019540:Area Under Curve; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000166:cytology; D002712:Chlorides / Q000378:metabolism; D004553:Electric Conductivity; D004558:Electric Stimulation / Q000379:methods; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D018682:GABA Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid