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J Neurophysiol (September 24, 2008). doi:10.1152/jn.90351.2008
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Submitted on March 10, 2008
Revised on August 8, 2008
Accepted on September 18, 2008

Conductances mediating intrinsic theta-frequency membrane potential oscillations in layer II parasubicular neurons

Stephen Douglas Glasgow1 and C. Andrew Chapman1*

1 Concordia University

* To whom correspondence should be addressed. E-mail: andrew.chapman{at}concordia.ca.

Ionic conductances that generate membrane potential oscillations in neurons of layer II of the parasubiculum were investigated 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 to 10 mV below spike threshold, indicating that they are mediated by voltage-dependent conductances. Application of tetrodotoxin (TTX) completely eliminated oscillations, suggesting that Na+ currents are required for the generation of the oscillations. Oscillations were not reduced by blocking Ca2+ currents with Cd2+ or Ca2+-free ACSF, or by blocking K+ conductances with either 50 µM or 5 mM 4-aminopyridine (4-AP), 30 mM tetraethylammonium (TEA), or Ba2+ (1-2 mM). Oscillations also persisted during blockade of the muscarinic-dependent K+ current, IM, using the selective antagonist XE-991 (10 µM). However, oscillations were significantly attenuated by blocking the hyperpolarization-activated cationic current Ih with Cs+ and were almost completely blocked by the more potent Ih blocker ZD7288 (100 µM). 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 Ih. 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.







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