Homeostatic regulation of rapid eye movement sleep by the preoptic area of the hypothalamus

  1. John J Maurer
  2. Alexandra Lin
  3. Xi Jin
  4. Jiso Hong
  5. Nicholas Sathi
  6. Romain Cardis
  7. Alejandro Osorio-Forero
  8. Anita Lüthi
  9. Franz Weber
  10. Shinjae Chung  Is a corresponding author
  1. Department of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, United States
  2. Department of Fundamental Neurosciences, University of Lausanne, Switzerland
8 figures and 2 additional files

Figures

Figure 1 with 2 supplements
POAGAD2→TMN neurons are most active during rapid eye movement sleep (REMs).

(A) Left, schematic of fiber photometry with simultaneous electroencephalogram (EEG) and electromyogram (EMG) recordings. Mouse brain figure adapted from the Allen Reference Atlas - Mouse Brain. …

Figure 1—figure supplement 1
POAGAD2→TMN axonal fibers are most active during rapid eye movement sleep (REMs).

Related to Figure 1. (A) Left, schematic of fiber photometry with simultaneous electroencephalogram (EEG) and electromyogram (EMG) recordings. Mouse brain figure adapted from the Allen Reference …

Figure 1—figure supplement 2
TMNHIS neurons are least active during sleep.

Related to Figure 1. (A) Left, schematic of fiber photometry with simultaneous electroencephalogram (EEG) and electromyogram (EMG) recordings. Middle, fluorescence image of TMN in an HDC-Cre mouse …

Figure 2 with 2 supplements
Inhibiting POAGAD2→TMN neurons reduces rapid eye movement sleep (REMs).

(A) Left, schematic of optogenetic inhibition experiments. Center left, fluorescence image of POA in a GAD2-CRE mouse injected with AAVretro-DIO-SwiChR++-eYFP into the TMN. Scale bar, 1 mm. Center …

Figure 2—figure supplement 1
Effects of inhibiting POAGAD2→TMN neurons on brain states and electroencephalogram (EEG).

Related to Figure 2. (A) Duration of rapid eye movement sleep (REMs), non-rapid eye movement sleep (NREMs), and wake episodes with and without laser stimulation in SwiChR++ and eYFP mice. (B) …

Figure 2—figure supplement 2
Effects of inhibiting TMNHIS neurons on brain states and electroencephalogram (EEG).

Related to Figure 2. (A) Left, schematic of optogenetic inhibition experiments. Center left, fluorescence image of TMN in HDC-Cre mouse injected with AAV2-EF1a-DIO-SwiChR++-eYFP into the TMN. Scale …

Figure 3 with 2 supplements
POAGAD2→TMN neurons exhibit an increased number of calcium transients during rapid eye movement sleep (REMs) restriction.

(A) Schematic of REMs restriction/rebound and photometry recording experiments. The brain state was continuously monitored; once a REMs episode was detected, we used a vibrating motor (zeitgeber …

Figure 3—figure supplement 1
Effects of rapid eye movement sleep (REMs) restriction on brain states and electroencephalogram (EEG).

Related to Figure 3. (A) Example session during REMs restriction (top) and REMs rebound (bottom) from the same mouse. Shown are EEG spectrogram, electromyogram (EMG) amplitude, motor vibration …

Figure 3—figure supplement 2
Rapid eye movement sleep (REMs) amount, duration, and frequency of episodes during photometry recordings combined with REMs restriction and rebound.

Related to Figure 3. (A) Percentage of REMs, duration, and frequency of REMs episodes during REMs restriction (green, zeitgeber time [ZT] 6.5–7.5) and baseline recordings (gray, ZT 6.5–7.5). Paired …

Figure 4 with 1 supplement
Inhibition of POAGAD2→TMN neurons during rapid eye movement sleep (REMs) restriction attenuates the REMs rebound.

(A) Schematic of REMs restriction/rebound and optogenetic inhibition experiments. During closed-loop REMs restriction (zeitgeber time [ZT] 1.5–7.5), a vibrating motor attached to the mouse head was …

Figure 4—figure supplement 1
Duration and frequency of rapid eye movement sleep (REMs) episodes and electroencephalogram (EEG) power during SwiChR++-mediated inhibition combined with REMs restriction and rebound.

Related to Figure 4. (A) Duration of REMs, non-rapid eye movement sleep (NREMs), and wake episodes during the last 3 hr of REMs restriction with laser stimulation (zeitgeber time [ZT] 4.5–7.5) in …

Author response image 1
Location of virus expression (A) and optic fiber placement (B) within subregions of POA.

Mouse brain figure adapted from the Allen Reference Atlas - Mouse Brain.

Author response image 2
Cumulative amount of REMs during REMs deprivation and rebound combined with optogenetic stimulation in eYFP and SwiChR groups.

This data is shown as bar graphs in Figure 4.

Author response image 3
Inhibiting POA GAD2→ TMN neurons at ZT5-8 reduces REMs.

(A) Schematic of optogenetic inhibition experiments. Mouse brain figure adapted from the Allen Reference Atlas - Mouse Brain. (B) Percentage of time spent in REMs, NREMs and wakefulness with laser …

Author response image 4
ΔF/Factivity of POA GAD2→TMN neurons during NREMs.

The duration of NREMs episodes was normalized in time, ranging from 0 to 100%. Shading, ± s.e.m. Pairwise t-tests with Holm-Bonferroni correctionp = 5.34 e-4 between80 and100. Graybar, intervals …

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