GABAB receptor-dependent modulation of network activity in the rat prefrontal cortex in vitro.
GABA (gamma-aminobutyric acid) can mediate inhibition via pre- and post/extrasynaptic GABA receptors. In this paper we demonstrate potentially post/extrasynaptic GABA(B) receptor-dependent tonic inhibition in L2/3 pyramidal cells of rat medial prefrontal cortex (mPFC) in vitro. First, we show via voltage-clamp experiments the presence of a tonic GABA(B) receptor-dependent outward current in these neurons. This GABA(B)ergic current could be induced by ambient GABA when present at sufficient concentrations. To increase ambient GABA levels in the usually silent slice preparation, we amplified network activity and hence synaptic GABA release with a modified artificial cerebrospinal fluid. The amplitude of tonic GABA(B) current was similar at different temperatures. In addition to the tonic GABA(B) current, we found presynaptic GABA(B) effects, GABA(B)-mediated inhibitory postsynaptic currents and tonic GABA(A) currents. Second, we performed current-clamp experiments to evaluate the functional impact of GABA(B) receptor-mediated inhibition in the mPFC. Activating or inactivating GABA(B) receptors led to rightward (reduction of excitability) or leftward (increase of excitability) shifts, respectively, of the input-output function of mPFC L2/3 pyramidal cells without effects on the slope. Finally, we showed in electrophysiological recordings and epifluorescence Ca(2+)-imaging that GABA(B) receptor-mediated tonic inhibition is capable of regulating network activity. Blocking GABA(B) receptors increased the frequency of excitatory postsynaptic currents impinging on a neuron and prolonged network upstates. These results show that ambient GABA via GABA(B) receptors is powerful enough to modulate neuronal excitability and the activity of neural networks.
Department of Physiology, University of Bern, Bern, Switzerland.
Ying
Y
Wang
Florian B
FB
Neubauer
Hans-Rudolf
HR
Lüscher
Kay
K
Thurley
D000818:Animals; D002118:Calcium / Q000378:metabolism; D046169:Dermoscopy; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D002118:Calcium