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@ARTICLE{Datunashvili:857201,
author = {Datunashvili, Maia and Chaudhary, Rahul and Zobeiri,
Mehrnoush and Lüttjohann, Annika and Mergia, Evanthia and
Baumann, Arnd and Balfanz, Sabine and Budde, Björn and van
Luijtelaar, Gilles and Pape, Hans-Christian and Koesling,
Doris and Budde, Thomas},
title = {{M}odulation of {H}yperpolarization-{A}ctivated {I}nward
{C}urrent and {T}halamic {A}ctivity {M}odes by {D}ifferent
{C}yclic {N}ucleotides},
journal = {Frontiers in cellular neuroscience},
volume = {12},
issn = {1662-5102},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {FZJ-2018-06438},
pages = {369},
year = {2018},
abstract = {The hyperpolarization-activated inward current, Ih, plays a
key role in the generation of rhythmic activities in
thalamocortical (TC) relay neurons. Cyclic nucleotides, like
3′,5′-cyclic adenosine monophosphate (cAMP), facilitate
voltage-dependent activation of hyperpolarization-activated
cyclic nucleotide-gated (HCN) channels by shifting the
activation curve of Ih to more positive values and thereby
terminating the rhythmic burst activity. The role of
3′,5′-cyclic guanosine monophosphate (cGMP) in
modulation of Ih is not well understood. To determine the
possible role of the nitric oxide (NO)-sensitive
cGMP-forming guanylyl cyclase 2 (NO-GC2) in controlling the
thalamic Ih, the voltage-dependency and
cGMP/cAMP-sensitivity of Ih was analyzed in TC neurons of
the dorsal part of the lateral geniculate nucleus (dLGN) in
wild type (WT) and NO-GC2-deficit (NO-GC2−/−) mice.
Whole cell voltage clamp recordings in brain slices revealed
a more hyperpolarized half maximal activation (V1/2) of Ih
in NO-GC2−/− TC neurons compared to WT. Different
concentrations of 8-Br-cAMP/8-Br-cGMP induced dose-dependent
positive shifts of V1/2 in both strains. Treatment of WT
slices with lyase enzyme (adenylyl and guanylyl cyclases)
inhibitors (SQ22536 and ODQ) resulted in further
hyperpolarized V1/2. Under current clamp conditions
NO-GC2−/− neurons exhibited a reduction in the
Ih-dependent voltage sag and reduced action potential firing
with hyperpolarizing and depolarizing current steps,
respectively. Intrathalamic rhythmic bursting activity in
brain slices and in a simplified mathematical model of the
thalamic network was reduced in the absence of NO-GC2. In
freely behaving NO-GC2−/− mice, delta and theta band
activity was enhanced during active wakefulness (AW) as well
as rapid eye movement (REM) sleep in cortical local field
potential (LFP) in comparison to WT. These findings indicate
that cGMP facilitates Ih activation and contributes to a
tonic activity in TC neurons. On the network level basal
cGMP production supports fast rhythmic activity in the
cortex.},
cin = {ICS-4},
ddc = {610},
cid = {I:(DE-Juel1)ICS-4-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30405353},
UT = {WOS:000448147900001},
doi = {10.3389/fncel.2018.00369},
url = {https://juser.fz-juelich.de/record/857201},
}