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Abstract

 
Abstract No.:A-B1027
Country:Canada
  
Title:CONDUCTANCES MEDIATING INTRINSIC SUBTHRESHOLD MEMBRANE POTENTIAL OSCILLATIONS IN LAYER II NEURONS OF THE PARASUBICULUM.
  
Authors/Affiliations:1 Stephen Glasgow*; 1 Andrew Chapman;
1 Concordia University, Montreal, QC, Canada
  
Content:Objectives: The parasubiculum receives synaptic inputs from the hippocampus and anterior thalamus and projects exclusively to layer II of the entorhinal cortex. It is thus well-poised to play a significant role in spatial and mnemonic processing associated with the hippocampal formation. We have previously demonstrated that layer II cells of the parasubiculum display intrinsic membrane potential oscillations at theta-frequency when depolarized to near-threshold voltage levels, but the mechanisms that underlie these oscillations are unknown. Methods and Materials: Whole-cell current clamp recordings were used to investigate the ionic conductances responsible for the generation of theta-frequency membrane potential oscillations in layer II parasubicular neurons. Results: The oscillations were eliminated by blockade of Na+ channels using tetrodotoxin (0.5 然), suggesting that Na+ currents contribute to the generation of the depolarizing phase of oscillations. Blockade of Ca2+ currents using cadmium (Cd2+, 100 然), or use of Ca2+-free ACSF, failed to alter the oscillations, suggesting that Ca2+ currents are not required. To investigate the role of K+ conductances, K+ channel antagonists tetraethylammonium (TEA, 30 mM), barium (Ba2+, 2 mM) and 4-aminopyridine (4-AP, 50 然 or 1 mM) were applied in the presence of synaptic antagonists kynurenic acid (1 mM) and bicuculline (25 然). Both doses of 4-AP failed to significantly reduce the power of oscillations, indicating that voltage-gated K+ channels do not contribute to the generation of the oscillations. Blockade of TEA-sensitive K+ conductances also did not significantly reduce the power of oscillations. In addition, blockade of inward-rectifying K+ currents with Ba2+ did not significantly reduce the power of oscillations. Recent evidence has suggested that the K+ current Im, which is blocked by muscarinic activation, may play a role in regulating neuronal excitability and theta-frequency resonance in CA1 pyramidal cells and in layer V entorhinal neurons. However, selective blockade of Im using XE991 failed to disrupt the oscillations, suggesting that Im is not involved in the generation of these oscillations in layer II parasubicular neurons. Subthreshold membrane potential oscillations in stellate cells of the entorhinal cortex are generated by an interaction between a persistent Na+ current and a hyperpolarization-activated inward cationic current (Ih). Blockade of Ih using cesium (Cs+, 1-2 mM with kynurenic acid and bicuculline) resulted in a significant reduction of the oscillations, and the selective Ih blocker ZD7288 (100 然) also eliminated the oscillations. Conclusions: These findings suggest that intrinsic membrane potential oscillations in layer II neurons of the parasubiculum are generated mainly through an interplay between a persistent sodium conductance and Ih. These voltage-dependent conductances provide a mechanism for membrane potential oscillations that can help support rhythmic network activity within the parasubiculum during theta-related behaviors.
  
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