The Brain Network in a Model of Thalamocortical Dysrhythmia.

Zobeiri M, van Luijtelaar G, Budde T, Sysoev IV

Abstract

Sensory information processing and higher cognitive functions rely on the interactions between thalamus and cortex. Many types of neurological and psychiatric disorders are accompanied or driven by alterations in the brain connectivity. In this study, putative changes in functional and effective corticocortical (CC), thalamocortical (TC), and corticothalamic (CT) connectivity during wakefulness and slow-wave sleep (SWS) in a model of thalamocortical dysrhythmia, TRIP8b−/− mice, and in control (wild-type or WT) mice are described. Coherence and nonlinear Granger causality (GC) were calculated for twenty 10 s length epochs of SWS and active wakefulness (AW) of each animal. Coherence was reduced between 4 and ca 20 Hz in the cortex and between cortex and thalamus during SWS compared with AW in WT but not in TRIP8b−/− mice. Moreover, TRIP8b−/− mice showed lower CT coherence during AW compared with WT mice; these differences were no longer present during SWS. Unconditional GC analysis also showed sleep-related reductions in TC and CT couplings in WT mice, while TRIP8b−/− mice showed diminished wake and enhanced sleep CC coupling and rather strong CT-directed coupling during wake and sleep, although smaller during sleep. Conditional GC coupling analysis confirmed the diminished CC and enhanced CT coupling in TRIP8b−/− mice. Our findings indicate that altered properties of hyperpolarization-activated cyclic nucleotide-gated cation channels, characterizing TRIP8b−/− mice, have clear effects on CC, TC, and CT networks. A more complete understanding of the function of the altered communication within these networks awaits detailed phenotyping of TRIP8b−/− mice aimed at specifics of sensory and attentional processes.