TY - JOUR
T1 - Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels
AU - Zobeiri, Mehrnoush
AU - Chaudhary, Rahul
AU - Datunashvili, Maia
AU - Heuermann, Robert J.
AU - Lüttjohann, Annika
AU - Narayanan, Venu
AU - Balfanz, Sabine
AU - Meuth, Patrick
AU - Chetkovich, Dane M.
AU - Pape, Hans Christian
AU - Baumann, Arnd
AU - van Luijtelaar, Gilles
AU - Budde, Thomas
N1 - Funding Information:
Acknowledgements The authors thank Elke Naß, Alexandra Mar-kovic, Katrin Foraita, Julia Schröer and Svetlana Kiesling for excellent technical assistance. This work has been supported by Deutsches Forschungsgemeinschaft (DFG, BU 1019/15-1), Interdisziplinäres Zentrum für Klinische Forschung Münster (IZKF, Bud3/001/16) and National Institutes of Health (NIH) grants NS059934 and GM008152. Rahul Chaudhary and Maia Datunashvili were DAAD fellows. This work was done in partial fulfillment of the Ph.D. thesis of Mehrnoush Zobeiri.
Funding Information:
TB designed and supervised the project, interpreted data, reviewed all experimental work and wrote the manuscript. MZ designed and performed experiments and analyzed data and wrote the manuscript. RCH performed experiments, analyzed data and did the mathematical modeling. MD performed experiments and analyzed data. GVL supervised the in vivo part of the experiments, interpreted data and wrote the manuscript. AB and SB performed cAMP quantification. AB wrote the manuscript. RJH, DMC. and HCP gave important intellectual and scientific input and provided material. AL and VN performed parts of the in vivo experiments. PM did data analysis. All authors revised the manuscript and approved the final version of the manuscript. The authors thank Elke Na?, Alexandra Markovic, Katrin Foraita, Julia Schr?er and Svetlana Kiesling for excellent technical assistance. This work has been supported by Deutsches Forschungsgemeinschaft (DFG, BU 1019/15-1), Interdisziplin?res Zentrum f?r Klinische Forschung M?nster (IZKF, Bud3/001/16) and National Institutes of Health (NIH) grants NS059934 and GM008152. Rahul Chaudhary and Maia Datunashvili were DAAD fellows. This work was done in partial fulfillment of the Ph.D. thesis of Mehrnoush Zobeiri. The authors declare that they have no conflict of interest.
Publisher Copyright:
© 2017, The Author(s).
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, Ih, in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in Ih current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b−/−). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K+ current, IA, in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5–4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings.
AB - Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, Ih, in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in Ih current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b−/−). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K+ current, IA, in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5–4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings.
KW - Delta oscillations
KW - HCN channels
KW - I
KW - In vivo
KW - Knockout mice
KW - Thalamocortical oscillations
KW - TRIP8b
UR - https://www.scopus.com/pages/publications/85034652048
U2 - 10.1007/s00429-017-1559-z
DO - 10.1007/s00429-017-1559-z
M3 - Article
C2 - 29168010
AN - SCOPUS:85034652048
SN - 1863-2653
VL - 223
SP - 1537
EP - 1564
JO - Brain Structure and Function
JF - Brain Structure and Function
IS - 3
ER -