The transition from wakefulness to a nonrapid eye movement (NREM) sleep state at the onset of sleep involves a transition from low-voltage, high-frequency irregular electroencephalography (EEG) waveforms to large-amplitude, low-frequency EEG waveforms accompanying synchronized oscillatory activity in the thalamocortical circuit. The thalamocortical circuit consists of reciprocal connections between the thalamus and cortex. The cortex sends strong excitatory feedback to the thalamus, however the function of which is unclear. In this study, we investigated the role of the thalamic metabotropic glutamate receptor 1 (mGluR1)-phospholipase C β4 (PLCβ4) pathway in sleep control in PLCβ4-deficient (PLCβ4-/-) mice. The thalamic mGluR1-PLCβ4 pathway contains synapses that receive corticothalamic inputs. In PLCβ4-/- mice, the transition from wakefulness to the NREM sleep state was stimulated, and the NREM sleep state was stabilized, which resulted in increased NREM sleep. The power density of delta (δ) waves increased in parallel with the increased NREM sleep. These sleep phenotypes in PLCβ4-/- mice were consistent in TC-restricted PLCβ4 knockdown mice. Moreover, in vitro intrathalamic oscillations were greatly enhanced in the PLCβ4-/- slices. The results of our study showed that thalamic mGluR1-PLCβ4 pathway was critical in controlling sleep architecture.
Bibliographical noteFunding Information:
This work was supported by NRF-2014R1A2A2A01006940 and NRF-2014M3A7B4051596, which was funded by the government of the Republic of Korea (Ministry of Science, ICT & Future Planning); the International Collaborative R&D Program, which was funded by the Ministry of Trade, Industry and Energy, Korea; Yonsei University Future-Leading Research Initiative of 2015 (2015-22-0163) and the Brain Korea 21(BK21) PLUS program. Joohyeon Hong and Go Eun Ha are fellowship awardee by BK21 PLUS program.
© 2016 The Author(s).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cellular and Molecular Neuroscience