Mechanism Of Noradrenaline Modulates The Simple Spike Activity Of Cerebellar Puekinje Cells In Mice

[Objective]In the cerebellum,the monoamine neurotransmitter noradrenaline(Noradrenaline,NA)mainly comes from the projection of the locus coeruleus(LC).NA can bidirectionally regulate Purkinjie cells(PC)simple spike(SS)discharge activity,but the mechanism is not clear.In the present study,we examined the effect and mechanism of NA on the SS activity of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods.[Methods]1.In vivoICR mice were anesthetized with urethane(intraperitoneal injection).The mice were tracheotomized and fixed on a custom-made stereotaxic frame.Craniotomy was drilled to expose the cerebellar surface.The brain surface was constantly superfused with oxygenated artificial cere-brospinal fluid(ACSF).The spontaneous firing activity of PC in vermis area of cerebellar cortex was recorded by cell-attached recording method.2.In vitroICR mice were anesthesia with isoflurane inhalation,the head was quickly severed and the brain was extracted.Then,sagittal sections were prepared with a vibrating slicer with a thickness of 300 microns.At 24-25 degrees Celsius,cerebellar sections were incubated for more than 60 minutes in ACSF mixed with 95%O2 and 5%CO2 for electrophysiological recording.Recorded the activity of PC by whole-cell recording,stimulate the climbing fiber(CF)to induce the PC to produce complex spike(CS),stimulate the parallel fibers(PF)to induce the PC to produce PF-PC excitatory postsynaptic current(PF-PC EPSC).[Results]1.Application of NA can significantly reduce the SS frequency,but the frequency of spontaneous CS was not changed,it also reduce the number of spikelets and the area under curve(AUC)of spontaneous CS.2.With the blockade of GABAA receptors,NA instead increase the frequency of SS,but not the frequency of CS,it also reduce the number of spikelets and AUC of spontaneous CS in vivo in mice;In vitro,fixed CS number and discharge frequency,NA still increase SS frequency and decrease spikelets number and after hyperpolarization potential(AHP)of CS.3.With the blockade of GABAA receptors,NA decrease the amplitude of PF-PC excitatory postsynaptic current(PF-PC EPSC),accompanied with a significant increase in paired-pulse ratio(PPR).4.Application the antagonist of a2-adrenergic receptor obviously inhibit the enhancement of NA on SS,while the α2-AR agonist can simulate the effect of NA on the increase of SS frequency,while the β-AR blocker did not significantly affect the enhancement of NA.5.Blocking of GABAA and AMPA receptors can eliminate the effect of NA on SS.[Conclusion]NA neurons could affect the information integration and transmission of PC via modulating afferent information from the inferior olivary nucleus projected onto the cerebellar cortex CF.