To investigate the effects of clesmatine on the myelination and neural oscillation-related firing activities during sleep in the hippocampus of adult APP/PS1 mice.

Oral administration of clemastine in drinking water was given to APP/PS1 mice for 3 months to enhance myelination in adulthood. Based on the treatment regimens, the mice were randomly assigned into APP/PS1 group, APP/PS1+clemastine group, and wild-type (WT) group. Local field potentials combined with three-dimensional acceleration of the head and neck were employed to determine the brain states, that is, wakefulness, non-rapid eye movement (NREM) sleep, REM sleep. In vivo multi-electrode arrays were utilized to continuously monitor neuronal firing activities in the dorsal hippocampus across the 3 sleep states.

① Oral clemastine administration via drinking water significantly increased MBP⁺ protein expression levels in APP/PS1+Clemastine mice than the APP/PS1 controls (P < 0.001). ② Clemastine administration did not alter the time proportions of NREM sleep, REM sleep and wakefulness during the daytime phase in APP/PS1 mice (P_s > 0.05). ③ Clemastine administration obviously reduced the mean firing rate of hippocampal pyramidal cells (P < 0.05) while increasing that of hippocampal interneurons (P < 0.05) in APP/PS1 mice. ④ Clemastine administration increased the occurrence rate of hippocampal sharp wave-ripple (SWR) oscillations during NREM sleep and specifically reduced the firing rate of pyramidal cells during SWR oscillations in APP/PS1 mice (P < 0.05). ⑤ Clemastine administration had no significant effect on the P hippocampal neuronal firing activity during theta oscillation in REM sleep in APP/PS1 mice (P_s > 0.05).

Clemastine administration not only enhances the adult myelination, but also rescues both the SWRs and associated hippocampal neuronal firing during NREM sleep in APP/PS1 mice.

To investigate the difference of dentate gyrus（DG）neuronal activity between wakefulness and sleep state, and the characteristics of DG neuronal activity during hippocampal sharp wave ripple and θ oscillations.

Six 3-month-dd male wild-type C57BL/6 mice（22~25 g）were employed. The oscillation state of local field potential in the dorsal hippocampus and three-dimensional acceleration of the head and neck were used to determine the brain state which were classified into three types: wakefulness, non-rapid eye movement（NREM）sleep and rapid eye movement（REM）sleep. In vivo multi-electrode arrays were utilized to record the firing activity of DG neurons under distinct states.

The DG neurons were divided into the granule cells, mossy cells and interneurons according to characteristics of spike rates and valley-to-peak spike waveform width. The firing rates of granule cells（n=75）in NREM sleep were significantly higher than those in either REM sleep（P<0.05）or wakefulness（P<0.05）. The granule cells exhibited further elevated spike activity during sharp wave ripples during NREM sleep and θ oscillations during REM sleep（P<0.05）. The firing rates of mossy cells（n=27）in REM sleep were significantly higher than in either NREM sleep（P<0.05）or wakefulness（P<0.05）, but no statistical difference was observed in firing rates between NREM sleep and wakefulness. Likewise, the mossy cells exhibited increased spike activity during sharp wave ripples in NREM sleep and θ oscillations in REM sleep（P<0.05）. The firing rates of interneurons（n=9）during REM sleep were significantly higher than that in NREM sleep（P<0.05）. However, there was no significant difference in spike activities of interneurons between NREM sleep and wakefulness. 67% of the DG interneurons increased their spike activities, whereas the remaining interneurons（33%）decreased their spike activities during sharp wave ripples. The spike activity of interneurons had greatest decline among 3 types of DG neurons（P<0.05）.

The granule cells and mossy cells in the DG area are significantly different between wakefulness and sleep states in the firing activities. The granule cells exhibit strongest firing activities during NREM sleep, whereas the mossy cells show strongest firing activities during REM sleep.

To investigate the characteristics of ventromedial thalamus (VM) neuronal activity during sleep-wake cycles.

Both the oscillation state of electrical activity in the parietal cortex and three-dimensional acceleration of the head and neck were employed to determine the brain states of male mouse (n=4). The brain states were classified into three types: wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. In vivo multi-electrode arrays were utilized to record the firing activity of VM and ventrolateral thalamus (VL) neurons in these three distinctive brain states and during their switching process.

①The firing rates of VM neurons (n=50) during wakefulness (4.13±0.47) Hz were significantly higher than in either NREM sleep (2.46±0.34 Hz, P<0.01) or REM sleep (2.35±0.32 Hz, P<0.01). There was no significant difference as to the firing rates between NREM and REM sleep state (P>0.05). ②The firing rates of VM neurons (n=50) increased significantly from NREM sleep state to wakefulness (P<0.001) and evidently reduced from wakefulness to NREM sleep state (P<0.01). However, there was no obvious difference from NREM sleep state to REM sleep state (P>0.05). ③The firing rates of VL neurons (n=40) during NREM sleep state (3.68±0.62) Hz were lower than in either wakefulness (10.42±1.03 Hz, P<0.01) or REM sleep condition (8.95±0.89 Hz, P<0.01). In contrast, the firing rates of VL neurons significantly increased from NREM sleep stated to either wakefulness (P<0.01) or REM sleep state (P<0.01).

The wakefulness state has the greatest firing activities of VM neurons. The firing activities of VM neurons reduce during the transition from wakefulness to sleep state, whereas the activities increase during the transition from sleep state to wakefulness state.