Conductances mediating intrinsic theta-frequency membrane potential oscillations in layer II parasubicular neurons.
Ionic conductances that generate membrane potential oscillations in neurons of layer II of the parasubiculum were studied using whole cell current-clamp recordings in horizontal slices from the rat brain. Blockade of ionotropic glutamate and GABA synaptic transmission did not reduce the power of the oscillations, indicating that oscillations are not dependent on synaptic inputs. Oscillations were eliminated when cells were hyperpolarized 6-10 mV below spike threshold, indicating that they are mediated by voltage-dependent conductances. Application of TTX completely eliminated oscillations, suggesting that Na(+) currents are required for the generation of the oscillations. Oscillations were not reduced by blocking Ca(2+) currents with Cd(2+) or Ca(2+)-free artificial cerebrospinal fluid, or by blocking K(+) conductances with either 50 microM or 5 mM 4-aminopyridine (4-AP), 30 mM tetraethylammonium (TEA), or Ba(2+)(1-2 mM). Oscillations also persisted during blockade of the muscarinic-dependent K(+) current, I(M), using the selective antagonist XE-991 (10 microM). However, oscillations were significantly attenuated by blocking the hyperpolarization-activated cationic current I(h) with Cs(+) and were almost completely blocked by the more potent I(h) blocker ZD7288 (100 microM). Intrinsic membrane potential oscillations in neurons of layer II of the parasubiculum are therefore likely driven by an interaction between an inward persistent Na(+) current and time-dependent deactivation of I(h). These voltage-dependent conductances provide a mechanism for the generation of membrane potential oscillations that can help support rhythmic network activity within the parasubiculum during theta-related behaviors.
Glasgow
Stephen D
SD
Ctr. for Studies in Behavioral Neurobiology, Dept. of Psychology, Concordia Univ., 7141 Sherbrooke St. W., Rm. SP-244, Montréal, Québec, Canada H4B 1R6.
Chapman
C Andrew
CA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013826:Theta Rhythm / Q000187:drug effects
D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D026902:Potassium Channel Blockers; D011412:Propanolamines; D011743:Pyrimidines; D026941:Sodium Channel Blockers; C082246:ICI D2788; C085075:CGP 55845A; D013779:Tetrodotoxin; D015761:4-Aminopyridine; D007736:Kynurenic Acid; D001640:Bicuculline