Kainate receptor subunit diversity underlying response diversity in retinal Off bipolar cells

Key points The temporal signals mediated by postsynaptic kainate receptors differ depending on subunit composition (GluK1–GluK5) and the presence of the auxiliary subunits Neto1 and Neto2. In ground squirrel retina, four anatomical types of Off bipolar cells can be divided into two functional groups, cb1a/b and cb3a/b, based on differences in the temporal responses of their kainate receptors to cone glutamate release; the kainate receptor subunits expressed by the two groups are not known. Our pharmacological results suggests that cb1 and cb3 cells both express the GluK1 subunit, a finding corroborated in cb3 cells by in situ hybridization with a GluK1‐specific probe. Additional results from pharmacology, in situ hybridization and immunohistochemistry suggest that the temporal differences in receptor responses may arise through the selective expression in cb3 cells of GluK3, GluK5, and Neto1. These results establish a relationship between kainate receptor subunit composition and parallel signal processing at the cone photoreceptor synapse.Abstract Postsynaptic kainate receptors mediate excitatory synaptic transmission over a broad range of temporal frequencies. In heterologous systems, the temporal responses of kainate receptors vary when different channel‐forming and auxiliary subunits are co‐expressed but how this variability relates to the temporal differences at central synapses is incompletely understood. The mammalian cone photoreceptor synapse provides advantages for comparing the different temporal signalling roles of kainate receptors, as cones release glutamate over a range of temporal frequencies, and three functionally distinct Off bipolar cell types receive cone signals at synapses that contain either AMPA or kainate receptors, all with different temporal properties. A disadvantage is that the different receptor subunits are not identified. We used in situ hybridization, immunocytochemistry, and pharmacology to identify the kainate receptor and auxiliary subunits in ground squirrel ( Ictidomys tridecimlineatus ) cb1a/b, cb2, and cb3a/b Off bipolar cell types. As expected, the types showed distinct subunit expression patterns. Kainate receptors mediated ∼80% of the synaptic response in cb3a/b cells and were heteromers of GluK1 and GluK5. Cb3a/b cells contained message for GluK1 and GluK5, and also GluK3 and the auxiliary subunit Neto1. The synaptic responses in cb1a/b cells were mediated by GluK1‐containing kainate receptors that behaved differently from the receptors expressed by cb3a/b cells. AMPA receptors mediated the entire synaptic response in cb2 cells and the remaining synaptic response in cb3a/b cells. We conclude that GluK1 is the predominant kainate receptor subunit in cb1 and cb3 Off bipolar cells. Different temporal response properties may result from selective association with GluK3, GluK5, or Neto1.