Dual GABAergic synaptic response of fast excitation and slow inhibition in the medial habenula of rat epithalamus.
We report here a novel action of GABAergic synapses in regulating tonic firing in the mammalian brain. By using gramicidin-perforated patch recording in rat brain slices, we show that cells of the medial habenula of the epithalamus generate tonic firing in basal conditions. The GABAergic input onto these cells at postnatal days 18-25 generates a combinatorial activation of fast excitation and slow inhibition. The fast excitation, mediated by gamma-aminobutyric acid type A receptors (GABA A Rs), is alone capable of triggering robust action potentials to increase cell firing. This excitatory influence of GABAergic input results from the Cl(-) homeostasis that maintains intracellular Cl(-) at high levels. The GABA A excitation is often followed by a slow inhibition mediated by GABA B Rs that suppresses tonic firing. Interestingly, in a subpopulation of the cells, the GABA B inhibition exhibits a remarkably low threshold for synaptic activation in that low-strength GABAergic input often activates selectively the GABA B slow inhibition, whereas the GABA A excitation requires further increases in stimulus strength. Our study demonstrates that the dual activation of GABAergic excitation and inhibition through GABA A Rs and GABA B Rs generates distinct temporal patterns of cell firing that alter the cellular output in an activity-dependent manner.
Kim
Uhnoh
U
Department of Neurosurgery and Interdisciplinary Neuroscience Program, College of Medicine, Pennsylvania State University, Hershey, PA 17033-0850, USA. ukim@hmc.psu.edu
Chung
Lee-yup
LY
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology / Q000379:methods; D019261:Epithalamus / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D019262:Habenula / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014966:Xanthenes / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; C114624:LY 341495; D010721:Phosphinic Acids; D011412:Propanolamines; D011963:Receptors, GABA-A; D014966:Xanthenes; C085075:CGP 55845A; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline