Inhibition of Orexin Neurons Induces Sleep

Tsunematsu et al. · 2011

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Evidence (2)
Causal Control # Continue PAPER_TPL BIO
Optogenetic photoinhibition (halorhodopsin) of orexin neurons triggers non-REM sleep and reduces dorsal raphe firing.
"During orange light illumination of the hypothalamus, EEG power gradually increased and EMG power gradually decreased (Fig. 5A).... During the second half of the 60 s photic illumination period, all orexin/Halo transgenic mice showed SWS (n = 7) (Fig. 5G–I)."
In vivo orange light illumination of the hypothalamus induces SWS in mice during the light, but not dark, period, p. 10533
Direct, reversible inhibition of orexin neurons is sufficient to causally induce a systems-level transition into SWS, a strong example of interventional leverage over global brain state relevant to consciousness research and to potential causal tests in AI systems via analogous circuit-level manipulations .
"Here, acute silencing of orexin neurons induced a gradual decrease in the firing frequency in DR serotonergic neurons to the same level as observed in SWS."
Acute inhibition of orexin neurons decreased firing in DR neurons, p. 10537
The manipulation not only changes global state but also systematically reduces activity in a downstream arousal hub (dorsal raphe), strengthening the causal chain from intervention to network-level changes often sought in mechanistic consciousness studies and their AI analogues .
Figures
Figure 5 (p. 10535) : This figure shows that photoinhibiting orexin neurons during wakefulness leads to EEG/EMG signatures of SWS, illustrating causal control over state transitions relevant to consciousness-level changes .
Figure 7 (p. 10536) : Simultaneous recordings demonstrate that the causal manipulation depresses DR activity alongside SWS induction, linking targeted control to distributed network effects tied to arousal and conscious state regulation .
Tables
Table 3 (p. 10536) : Table 3. Episode duration of wakefulness, SWS, and REM sleep during light period of orexin/Halo transgenic mice and wild-type mice
Limitations: Photic inhibition failed to induce SWS during the dark period, suggesting circadian/homeostatic constraints and possible ceiling effects from other wake-promoting systems; thus, causal efficacy depends on background state and might not generalize across conditions .
State Transitions # Continue PAPER_TPL BIO
Brief optogenetic silencing of orexin neurons produces rapid, reversible switches between wakefulness and SWS.
"Immediately after the termination of orange light, firing in the DR neurons quickly recovered to the basal wakefulness level, and the EEG showed low amplitude, fast activity, and greater EMG levels indicative of wakefulness."
Photic inhibition of orexin neurons reduces firing of neurons in an orexin terminal field, p. 10533
The system shows fast, reversible switching—sleep onset during inhibition and wake signatures upon offset—consistent with abrupt state transitions central to theories of conscious access and metastability .
"During orange light illumination, EEG delta power gradually increased and EMG power gradually decreased (Fig. 7G,I,K)."
Photic inhibition of orexin neurons reduces firing of neurons in an orexin terminal field, p. 10533
This time-locked change during the perturbation evidences a controlled transition into a different processing regime, aligning with state transition markers used in consciousness and AI dynamics research .
Figures
Figure 7 (p. 10536) : The figure visualizes the switch into SWS during inhibition and the coupled decrease in DR firing, exemplifying abrupt regime change in brain dynamics .
Limitations: Transitions depended on time-of-day and sleep pressure, indicating that network state modulates susceptibility to induced switching, which may limit generalization across contexts .