Activity-Dependent Neurotrophin Signaling Underlies Developmental Switch of Ca2+ Channel Subtypes Mediating Neurotransmitter Release

作者：Miki Takafumi; Hirai Hirokazu; Takahashi Tomoyuki^*

来源：Journal of Neuroscience, 2013, 33(48): 18755-18763.

DOI：10.1523/JNEUROSCI.3161-13.2013

At the nerve terminal, neurotransmitter release is triggered by Ca2+ influx through voltage-gated Ca2+ channels (VGCCs). During postnatal development, VGCC subtypes in the nerve terminal switch at many synapses. In immature rodent cerebella, N-type and P/Q-type VGCCs mediate GABAergic neurotransmission from Purkinje cells (PCs) to deep nuclear cells, but as animals mature, neurotransmission becomes entirely P/Q-type dependent. We reproduced this developmental switch in rat cerebellar slice culture to address the underlying mechanism. Chronic block of cerebellar neuronal activity with tetrodotoxin (TTX) in slice culture, or in vivo, reversed the switch, leaving neurotransmission predominantly N-type channel-dependent. Brain-derived neurotrophic factor or neurotrophin-4 rescued this TTX effect, whereas pharmacological blockade of neurotrophin receptors mimicked the TTX effect. In PC somata, unlike in presynaptic terminals, TTX had no effect on the proportion of Ca2+ channel subtype currents. We conclude that neuronal activity activates the neurotrophin-TrkB signaling pathway, thereby causing the N-to-P/Q channel switch in presynaptic terminals.

• 出版日期2013-11-27