The molecular agents that induce
loss of consciousness during
anesthesia are classically believed to act by binding to cognate transmembrane receptors widely distributed in the CNS and critically suppressing local processing and network connectivity. However, previous work has shown that microinjection of
anesthetics into a localized region of the brainstem mesopontine tegmentum (
MPTA) rapidly and reversibly induces
anesthesia in the absence of global spread. This implies that functional extinction is determined by neural pathways rather than vascular distribution of the
anesthetic agent. But does clinical (systemic-induced)
anesthesia employ
MPTA-linked circuitry? Here we show that cell-selective lesioning of the
MPTA in rats does not, in itself, induce
anesthesia or
coma. However, it increases the systemic dose of
pentobarbital required to induce
anesthesia, in a manner proportional to the extent of the lesion. Such lesions also affect emergence, extending the duration of
anesthesia. Off-target and
sham lesions were ineffective. Combined with the prior microinjection data, we conclude that
drug delivery to the
MPTA is sufficient to induce
loss-of-consciousness and that neurons in this locus are necessary for
anesthetic induction at clinically relevant doses. Together, the results support an architecture for
anesthesia with the
MPTA serving as a key node in an endogenous network of dedicated pathways that switch between wake and unconsciousness. As such, the
MPTA might also play a role in
syncope, concussion and sleep.