Tonic current through GABAA receptors and hyperpolarization-activated cyclic nucleotide-gated channels modulate resonance properties of rat subicular pyramidal neurons.
The subiculum, considered to be the output structure of the hippocampus, modulates information flow from the hippocampus to various cortical and sub-cortical areas such as the nucleus accumbens, lateral septal region, thalamus, nucleus gelatinosus, medial nucleus and mammillary nuclei. Tonic inhibitory current plays an important role in neuronal physiology and pathophysiology by modulating the electrophysiological properties of neurons. While the alterations of various electrical properties due to tonic inhibition have been studied in neurons from different regions, its influence on intrinsic subthreshold resonance in pyramidal excitatory neurons expressing hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is not known. Using pharmacological agents, we show the involvement of α5βγ GABAA receptors in the picrotoxin-sensitive tonic current in subicular pyramidal neurons. We further investigated the contribution of tonic conductance in regulating subthreshold electrophysiological properties using current clamp and dynamic clamp experiments. We demonstrate that tonic GABAergic inhibition can actively modulate subthreshold properties, including resonance due to HCN channels, which can potentially alter the response dynamics of subicular pyramidal neurons in an oscillating neuronal network.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India.
Nirnath
N
Sah
Sujit K
SK
Sikdar
D000818:Animals; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D008959:Models, Neurological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D046509:Tissue Culture Techniques
D058787:GABA-A Receptor Antagonists; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D010852:Picrotoxin; D011963:Receptors, GABA-A; C511535:Gabra5 protein, rat
GABAA receptor current rectification; dynamic clamp; hippocampus; hyperpolarization-activated cyclic nucleotide-gated channels; theta frequency resonance