Noradrenergic Transmission System In CMT Regulates Emergence From Propofol Anesthesia In Rats

Objective At present,the mechanisms by which general anesthetics causing loss of consciousness remain unclear.The central medial thalamic nucleus(CMT)is a rarely studied component of the midline thalamic complex,which is deemed to be a part of the nonspecific arousal system.Despite the fact that CMT participates in modulating arousal and receives excitatory noradrenergic(NE)projections from locus coeruleus(LC),it remains unknown whether noradrenergic pathway in the CMT takes part in modulating the arousal system.Therefore,we hypothesized that noradrenergic transmission in the CMT is involved in modulating induction and emergence of propofol anesthesia.Methods Firstly,a CMT microinjection model of rat was established.All model rats were randomly divided into two groups: artificial cerebrospinal fluid group(ACSF)and norepinephrine(NE)group.Each group contained 10 rats.The effects of CMT microinjection of ACSF or NE on induction of anesthesia and recovery time were observed.Next,the effects of CMT microinjection of ACSF or NE on rat prefrontal cortex(PFC)and anterior cingulate cortex(ACC)electroencephalogram(EEG)were observed under continuous propofol anesthesia.Finally,the whole cell patch clamp was used to observe the effects of propofol and NE on CMT neuronal excitability and GABAergic inhibitory postsynaptic current(s IPSCs).Results CMT microinjection of ACSF had no effect on the induction and recovery time of propofol anesthesia in rats.CMT microinjection of NE had no effect on the sensitivity and induction time of propofol anesthesia in rats,but shortened the emergence time from propofol anesthesia.CMT microinjection of ACSF has no significant effect on PFC and ACC EEG in rats and microinjection of NE increased ?(4-8 Hz)ratio in PFC,without affecting other power.CMT microinjection of ACSF had no significant effect on PFC and ACC EEG in rats.However,NE decreased ?(1-4 Hz)ratio,increased ? and ?(8-12 Hz)ratio in ACC,without altering ?(12-25 Hz)and ?(25-60 Hz).Perfusion of propofol decreased the firing rate of action potential and made the membrane potential hyperpolarization in CMT neurons.Administration of propofol plus NE increased the firing rate of action potential and made the membrane potential depolarization in CMT neurons.Propofol increased the frequency and amplitude of s IPSCs,while NE decreased the frequency of s IPSCs,without changing the amplitude.Conclusions The noradrenergic transmission in the CMT is involved in modulating the emergence from propofol anesthesia and cortical EEG arousal,but not involved in the induction of propofol anesthesia.Propofol enhances the GABAergic transmission in the CMT through presynaptic and postsynaptic mechanisms,but NE partly attenuates the effects of propofol by reducing GABA release from presynaptic membrane.Propofol decreaed the excitability of CMT neurons,but NE partially reversed the inhibitory effect of propofol.