Physiological markers of local sleep

Abstract

Substantial evidence suggests that brain regions that have been disproportionately used during waking will require a greater intensity and/or duration of subsequent sleep. For example, rats use their whiskers in the dark and their eyes during the light, and this is manifested as a greater magnitude of electroencephalogram (EEG) slow-wave activity in the somatosensory and visual cortex during sleep in the corresponding light and dark periods respectively. The parsimonious interpretation of such findings is that sleep is distributed across local brain regions and is use-dependent. The fundamental properties of sleep can also be experimentally defined locally at the level of small neural assemblies such as cortical columns. In this view, sleep is orchestrated, but not fundamentally driven, by central mechanisms. We explore two physiological markers of local, use-dependent sleep, namely, an electrical marker apparent as a change in the size and shape of an electrical evoked response, and a metabolic marker evident as an evoked change in blood volume and oxygenation delivered to activated tissue. Both markers, applied to cortical columns, provide a means to investigate physiological mechanisms for the distributed homeostatic regulation of sleep, and may yield new insights into the consequences of sleep loss and sleep pathologies on waking brain function.

Figure 1

Typical evoked electrical responses (ERP) to auditory clicks in the rat. ERPs for wake, quiet sleep, and REM were averaged across stimuli and plotted across time (thick black lines). The gray regions illustrate the standard deviation from 100 trials. The vertical line represents the time of the stimulus. The ERP amplitude, measured from the first peak to the first trough, was significantly larger during quiet sleep than during both wake and REM.

Figure 2

Temporal changes in the amplitude of event-related potentials. Animals were presented with single auditory clicks randomly at intervals from 2 to 3 seconds and the size of each individual evoked response was measured and plotted across time (∼10 minutes of data from one rat are shown here). The dark gray trace shows an 8 point moving boxcar average over time, while the black trace shows the data smoothed with a 50 point moving boxcar average to illustrate the evoked response amplitude trend over time. The horizontal line represents the average response from all trials in the period. When the animal was awake (white background), the evoked response usually exhibited low amplitude. When the animal was in quiet sleep (gray background), the evoked response usually showed high amplitude. However, across time, the evoked response was highly variable, sometimes of high and sometimes of low amplitude.

Figure 3

Comparison of evoked response potentials from adjacent whisker barrels. When two rat whiskers were simultaneously stimulated, two evoked responses were generated over the corresponding whisker barrel cortical columns in the cortex. The average traces (top) showed that the evoked responses were almost identical on average, but the individual trials showed large variability both among trials (downwards) and between the two different whiskers (left traces vs. right traces).

Figure 4

Comparison of variability in a cortical column and its associated thalamic region. Evoked electrical responses from the rat whisker barrel cortical columns in the cortex (left panel) showed much higher variability than local field potentials recorded from the corresponding thalamic region that projects to the respective cortical column (right panel). The thick black line represents the average of all responses and the traces with varying shades of gray are the individual responses. Each response was generated by identically deflecting the rat whisker by 1mm in 0.2ms. The stimulus time is indicated by the vertical line.

Figure 5

Averaged evoked optical (lower panel) and electrical (upper panel) responses to a 10 Hz burst of five auditory clicks across wake, quiet sleep, and REM sleep. The responses showed significantly larger hemodynamic optical changes (as recorded by changes in 660 nm light absorption) during quiet sleep than during wake and REM. The electrical evoked responses followed a similar state-dependent trend as shown in Figure 1. The vertical scale bar indicates percent change from baseline, pre-stimulus conditions. An upward deflection in the evoked optical signal corresponded to a decrease in backscattered light, an increase in 660 nm light absorption, and an increase in deoxyhemoglobin and blood volume. Note the time scale differences between the electrical and optical plots. The five thin vertical lines correspond to each of the five auditory clicks.