GluD2 Endows Parallel Fiber-Purkinje Cell Synapses with a High Regenerative Capacity.

The glutamate receptor GluD2 expressed at parallel fiber (PF)-Purkinje cell (PC) synapses regulates the formation and maintenance of the synapses. To investigate the role of GluD2 in their extraordinarily high regenerative capacity, the process after surgical transection of PFs was compared between wild-type and GluD2-knock-out mice. We discovered that, in wild-type mice, PF synapses regenerate initially by inducing hypertrophic responses in surviving synaptic elements, and then by sprouting and elongation of PF collaterals. Subsequently, hypertrophied PF synapses remodel into compact synapses. In GluD2-knock-out mice, PF wiring remains in the degenerative phase, showing neither a hypertrophic response nor recovery of PF axons or synapses. Our finding thus highlights that synaptic connection in the adult brain can regenerate with aid of GluD2.