科研之友
微信
新浪微博
Facebook
分享链接
摘要
Parallel fiber synapses in the cerebellum express a wide range of presynaptic receptors. However, presynaptic receptor expression at individual parallel fiber synapses is quite heterogeneous, suggesting physiological mechanisms regulate presynaptic receptor expression. We investigated changes in presynaptic GABA(B) receptors at parallel fiber-stellate cell synapses in acute cerebellar slices from juvenile mice. GABA(B) receptor-mediated inhibition of excitatory postsynaptic currents (EPSCs) is remarkably diverse at these synapses, with transmitter release at some synapses inhibited by >50% and little or no inhibition at others. GABA(B) receptor-mediated inhibition was significantly reduced following 4 Hz parallel fiber stimulation but not after stimulation at other frequencies. The reduction in GABA(B) receptor-mediated inhibition was replicated by bath application of forskolin and blocked by application of a PKA inhibitor, suggesting activation of adenylyl cyclase and PKA are required. Immunolabeling for an extracellular domain of the GABA(B2) subunit revealed reduced surface expression in the molecular layer after exposure to forskolin. GABA(B) receptor-mediated inhibition of action potential evoked calcium transients in parallel fiber varicosities was also reduced following bath application of forskolin, confirming presynaptic receptors are responsible for the reduced EPSC inhibition. These data demonstrate that presynaptic GABA(B) receptor expression can be a plastic property of synapses, which may compliment other forms of synaptic plasticity. This opens the door to novel forms of receptor plasticity previously confined primarily to postsynaptic receptors.
- 出版日期2018-5
