Identification of the sleep-wake states in rats using the high-frequency activity of the electroencephalogram.

The electroencephalographic signal constitutes the main sign classically used for the identification of states of alertness. However, activities in the high frequency (>100 Hz) range have not been properly studied despite their high potential for sleep scoring in rodents. In the present study, we designed a method for the identification of the sleep-wake states in rats by exclusively using high-frequency activities of the electroencephalogram. By calculating the ratio between the amplitude of the electroencephalographic signal from 110 to 200 Hz and from 110 to 300 Hz, we obtained an index that had values that were low during wakefulness, intermediate during non-REM sleep and high during REM sleep. This high-frequency index (HiFI) allowed the identification of each state without the need to study other signs such as muscle activity or eye movements. To evaluate the performance of the index, we compared it with the conventional scoring of the sleep-wake cycle based upon the study of the electromyogram and delta (0.5-4 Hz), theta (6-9 Hz) and sigma (10-14 Hz) bands of the electroencephalogram. The index had an accuracy of 90.43 ± 1.91% (Cohen's kappa value of 0.82), confirming that the study of the high-frequency activities of the electroencephalogram was sufficient to reliably identify alertness states in the rat. Compared to other sleep-scoring methods, the HiFI has several advantages. It only requires one electroencephalography electrode, thus reducing the severity of the surgical preparation of the experimental animal, and its calculation is very simple, so it can be easily implemented online to classify sleep-wake states in real time.

Persistent ∆FosB expression limits recurrent seizure activity and provides neuroprotection in the dentate gyrus of APP mice.

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection to dentate granule cells, indicating that ∆FosB may act over long timescales to coordinate neuroprotective pathways. To test this hypothesis, we used viral-mediated expression of ∆JunD to interfere with ∆FosB signaling over the course of several months in transgenic mice expressing mutant human amyloid precursor protein (APP), which exhibit spontaneous seizures and develop AD-related neuropathology and cognitive deficits. Our results demonstrate that persistent ∆FosB activity acts through discrete modes of hippocampal target gene regulation to modulate neuronal excitability, limit recurrent seizure activity, and provide neuroprotection to hippocampal dentate granule cells in APP mice.

Temporal dynamics of the transition period between nonrapid eye movement and rapid eye movement sleep in the rat.

Study Objectives: We studied the sequence of events that occur in electroencephalogram (EEG), electromyogram (EMG), and ocular activities along the transition period between nonrapid eye movement and rapid eye movement (REM) sleep and their temporal relationships. Methods: Twenty adult Wistar rats underwent polygraphic recordings of EEG, EMG, and eye movements during the transition periods. The studied EEG variables included the time of occurrence of the last sleep spindle and the evolution of the amplitudes of δ (1-5 Hz), θ (6-9 Hz), and high-frequency (110-160 Hz) oscillations (HFO). Motor variables included the development of atonia in the acromiotrapezius muscle and the occurrence of the first REM. The phase-amplitude coupling between θ and HFO was also analyzed. Results: The transition periods started with the onset of θ, followed by HFO onset and the decline of δ activities. From onset, HFO amplitude was coupled to the phase of θ. The first REM and the last sleep spindle coincided with the complete extinction of δ. At that point, the muscle tonus started to decrease, reaching its atonia when HFO achieved maximum amplitude. Conclusions: As the development of HFO delimited the duration of all transitional changes with precision, it can be considered a good delimiter for the transition period. Furthermore, as transitional changes occurred in a precise sequence, alterations in their temporal dynamics could be of interest in the study of sleep disorders and pathologies.