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Characterisation of Hyperpolarization-Activated Currents (Ih) in the Medial Septum/Diagonal Band Complex in the Mouse
Brain Research
  • Neil P. Morris
  • Robert E.W. Fyffe, Wright State University - Main Campus
  • Brian Robertson
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Hyperpolarization-activated cyclic nucleotide gated (HCN) channel subunits are distributed widely, but selectively, in the central nervous system, and underlie hyperpolarization-activated currents (Ih) that contribute to rhythmicity in a variety of neurons. This study investigates, using current and voltage-clamp techniques in brain slices from young mice, the properties of Ih currents in medial septum/diagonal band (MS/DB) neurons. Subsets of neurons in this complex, including GABAergic and cholinergic neurons, innervate the hippocampal formation, and play a role in modulating hippocampal theta rhythm. In support of a potential role for Ih in regulating MS/DB firing properties and consequently hippocampal neuron rhythmicity, Ih currents were present in around 60% of midline MS/DB complex neurons. The Ih currents were sensitive to the selective blocker ZD7288 (10 μM). The Ih current had a time constant of activation of around 220 ms (at −130 mV), and tail current analysis revealed a half-activation voltage of −98 mV. Notably, the amplitude and kinetics of Ih currents in MS/DB neurons were insensitive to the cAMP membrane permeable analogue 8-bromo-cAMP (1 mM), and application of muscarine (100 μM). Immunofluoresence using antibodies against HCN1, 2 and 4 channel subunits revealed that all three HCN subunits are expressed in neurons in the MS/DB, including neurons that express the calcium binding protein parvalbumin (marker of fast spiking GABAergic septo-hippocampal projection neurons).The results demonstrate, for the first time, that specific HCN channel subunits are likely to be coexpressed in subsets of MS/DB neurons, and that the resultant Ih currents show both similarities, and differences, to previously described Ih currents in other CNS neurons.
Citation Information
Neil P. Morris, Robert E.W. Fyffe and Brian Robertson. "Characterisation of Hyperpolarization-Activated Currents (Ih) in the Medial Septum/Diagonal Band Complex in the Mouse" Brain Research Vol. 1006 Iss. 1 (2004) p. 74 - 86 ISSN: 0006-8993
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