Effects Of Noradrenaline On Sensory Stimulus-Evoked Responses In The Cerebellar Molecular Layer In Vivo In Mice

Objective:Abundant afferent fibers of locus coeruleus(LC)noradrenergic neurons project to the cerebellar cortex and deep cerebellar nuclei.Adrenergic receptors(ARs)are widely distributed in the cerebellar cortex.Application of noradrenaline(NA)to cerebellar cortex induced a decrease in spontaneous simple spike(SS)firing activity via enhancing both inhibitory inputs from molecular layer interneuron(MLI),and depressed spontaneous complex spike(CS)firing activity of Purkinje cell(PC)via activated a2-AR-protein kinase A(PKA)pathway in vivo in mice.NA plays a certain role in the process of integrating and processing a wide variety of information in the cerebellar cortex.However,the effects of NA on sensory information processing in the cerebellar molecular layer in living mouse have not yet been fully understood.Therefore,we examined the effects of exogenous NA on facial stimulation-evoked field potential responses in the cerebellar molecular layer and to explore the role of NA on sensory information processing in the cerebellar molecular layer.Methods:Adult ICR mice were selected and used urethane to anesthetize the mice for tracheal intubation.Mice were fixed with a custom-made stereotaxic frame,and the skull and the dura mater in cerebellar Crus Ⅱ were removed to perfuse the brain surface with artificial cerebrospinal fluid(ACSF)containing oxygen.Representative field potential responses simultaneously recorded in cerebellar molecular layer in response to air-puff(60 ms,60 psi)stimulus on ipsilateral whisker pad.Results:1)Application of NA at 25 μM of the cerebellar surface perfusion significantly reduced the amplitude(AMP),the area under curve(AUC)and decay time of facial stimulus-evoked inhibitory responses(PI)and excitatory response(N1),and increased the half width of the P1 and N1 in the cerebellar molecular layer.2)The NA-induced decrease in the amplitude of P1 was concentration-dependence.The 50%of inhibiting concentration was 10,94 μM.3)Both an antagonist of α2-AR,yohimbine,and an antagonist of α-AR,phentolamine,completely blocked the NA-induced inhibition of facial stimulation-evoked responses.And application of α2-adrenergic receptor agonist,UK14304 can mimic the NE-induced effect of inhibition.4)Application of al-AR antagonist,prazosin or β-AR antagonist,propranolol has no effect on the NA-induced inhibition of facial stimulation-evoked responses.Conclusion:LC-NA projecting fibers of cerebellum can inhibit glutamatergic and GABAergic responses induced by sensory stimulation through activating α2-AR,thus regulating the integration and transmission of sensory information in local cerebellar circuits.