Abstract:
: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, I h, in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I h 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, I A, 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.
journal_name
Brain Struct Functjournal_title
Brain structure & functionauthors
Zobeiri M,Chaudhary R,Datunashvili M,Heuermann RJ,Lüttjohann A,Narayanan V,Balfanz S,Meuth P,Chetkovich DM,Pape HC,Baumann A,van Luijtelaar G,Budde Tdoi
10.1007/s00429-017-1559-zsubject
Has Abstractpub_date
2018-04-01 00:00:00pages
1537-1564issue
3eissn
1863-2653issn
1863-2661pii
10.1007/s00429-017-1559-zjournal_volume
223pub_type
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