Differential distribution of Ca2+ channel subtypes at retinofugal synapses.

Retinofugal synapses serve as models for understanding how sensory signals from the periphery are relayed to the brain. Past studies have focused primarily on understanding the postsynaptic glutamatergic receptor subtypes involved in signal transmission, but the mechanisms underlying glutamate release at presynaptic retinal terminals remains largely unknown. Here we explored how different calcium (Ca2+) channel subtypes regulate glutamatergic excitatory synaptic transmission in two principal retinorecipient targets, the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) of the mouse. We used an in vitro slice preparation to record the synaptic responses of dLGN and SC neurons evoked by the electrical stimulation of optic tract (OT) fibers before and during the application of selective Ca2+ channel blockers. We found that synaptic responses to paired or repetitive OT stimulation were highly sensitive to extracellular levels of Ca2+ and to selective antagonists of voltage gated Ca2+ channels, indicating that these channels regulate the presynaptic release of glutamate at retinal synapses in both dLGN and SC. Bath application of selective Ca2+ channel blockers revealed that P/Q-type Ca2+ channels primarily operate to regulate glutamate release at retinal synapses in dLGN, while N-type Ca2+ channels dominate release in the SC.Significance Statement The retinofugal synapse serves as the preeminent model for understanding how sensory information from the external world is relayed to the brain. We explored the cellular mechanisms that regulate the presynaptic release of glutamate in two principal retinorecipient targets, the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) of mouse. Although the great majority of retinal ganglion cells have an axon that bifurcates and projects to both dLGN and SC, different Ca2+ channel subtypes regulate the presynaptic release of glutamate, with P/Q channels largely operating in dLGN, and N-type in SC. Because these subtypes possess a unique set of biophysical properties that can affect the efficacy of synaptic transmission, such nonuniform distribution promotes terminal specific modulation of neurotransmitter release.