Differential Localization of δ Glutamate Receptors in the Rat Cerebellum: Coexpression with AMPA Receptors in Parallel Fiber–Spine Synapses and Absence from Climbing Fiber–Spine Synapses

TLDR

δ2 glutamate receptors are highly expressed in Purkinje cells and are implicated in cerebellar long‑term depression, and their co‑localization with other receptors may enable direct interactions. The study aimed to determine the synaptic and subsynaptic localization of δ receptors in rat cerebellar cortex. This was achieved using sensitive, high‑resolution immunogold procedures. δ2 receptors are densely localized to parallel fiber–spine synapses on Purkinje cells, absent from other synapses such as climbing fiber–spine and parallel fiber–interneuron synapses; within the postsynaptic specialization they colocalize with AMPA GluR2/3 receptors and lack a presynaptic pool, indicating selective targeting to a subset of Purkinje cell spines.

Abstract

The δ2 glutamate receptors are prominently expressed in Purkinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of δ receptors in rat cerebellar cortex was investigated with sensitive and high-resolution immunogold procedures. After postembedding incubation with an antibody raised to a C-terminal peptide of δ2, high gold particle densities occurred in all parallel fiber synapses with Purkinje cell dendritic spines, whereas other synapses were consistently devoid of labeling. Among the types of immunonegative synapse were climbing fiber synapses with spines and parallel fiber synapses with dendritic stems of interneurons. At the parallel fiber–spine synapse, gold particles signaling δ receptors were restricted to the postsynaptic specialization. By the use of double labeling with two different gold particle sizes, it was shown that δ and AMPA GluR2/3 receptors were colocalized along the entire extent of the postsynaptic specialization without forming separate domains. The distribution of gold particles representing δ receptors was consistent with a cytoplasmic localization of the C terminus and an absence of a significant presynaptic pool of receptor molecules. The present data suggest that the δ2 receptors are targeted selectively to a subset of Purkinje cell spines and that they are coexpressed with ionotropic receptors in the postsynaptic specialization. This arrangement could allow for a direct interaction between the two classes of receptor.