Developmental enhancement of alpha(2)-adrenoceptor-mediated suppression of inhibitory synaptic transmission onto mouse cerebellar purkinje cells

作者：Hirono M^*; Matsunaga W; Chimura T; Obata K

来源：Neuroscience, 2008, 156(1): 143-154.

DOI：10.1016/j.neuroscience.2008.07.018

• clonidine
• development
• interneuron
• firing
• HCN
• action potential

Noradrenaline (NA) modulates glutamatergic and GABAergic transmission in various areas of the brain. It is reported that some alpha(2)-adrenoceptor subtypes are expressed in the cerebellar cortex and alpha(2)-adrenoceptors may play a role in motor coordination. Our previous study demonstrated that the selective alpha(2)-adrenoceptor agonist clonidine partially depresses spontaneous inhibitory postsynaptic currents (sIPSCs) in mouse cerebellar Purkinje cells (PCs). Here we found that the inhibitory effect of clonidine on sIPSCs was enhanced during postnatal development. The activation of alpha(2)-adrenoceptors by clonidine did not affect sIPSCs in PCs at postnatal days (P) 8-10, when PCs showed a few sIPSCs and interneurons in the molecular layer (MLIs) did not cause action potential (AP). In the second postnatal week, the frequency of sIPSCs increased temporarily and reached a plateau at P14. By contrast, MLIs began to fire at P11 with the firing rate gradually increasing thereafter and reaching a plateau at P21. In parallel with this rise in the rate of firing, the magnitude of the clonidine-mediated inhibition of sIPSCs increased during postnatal development. Furthermore, the magnitude of the clonidine-mediated firing suppression in MLIs, which seemed to be mediated by a reduction in amplitude of the hyperpolarization-activated nonselective cation current, I-h, was constant across development. Both alpha(2A)- and alpha(2B)-, but not alpha(2C)-, adrenoceptors were strongly expressed in MLIs at P13, and P31. Therefore, the developmental enhancement of the clonidine-mediated inhibition of sIPSCs is attributed to an age-dependent increase in AP-derived sIPSCs, which can be blocked by clonidine. Thus, presynaptic activation of alpha(2)-adrenoceptors inhibits cerebellar inhibitory synaptic transmission after the second postnatal week, leading to a restriction of NA signaling, which is mainly mediated by alpha(1)- and alpha(2)-adrenoceptors in the adult cerebellar neuronal circuit.

• 出版日期2008-9-22