Synaptic and Extrasynaptic Factors Governing Glutamatergic Retinal Waves

In the few days prior to eye-opening in mice, the excitatory drive underlying waves switches from cholinergic to glutamatergic. Here, we describe the unique synaptic and spatiotemporal properties of waves generated by the retina's glutamatergic circuits. First, knockout mice lacking vesicular glutamate transporter type 1 do not have glutamatergic waves, but continue to exhibit cholinergic waves, demonstrating that the two wave-generating circuits are linked. Second, simultaneous outside-out patch and whole-cell recordings reveal that retinal waves are accompanied by transient increases in extrasynaptic glutamate, directly demonstrating the existence of glutamate spillover during waves. Third, the initiation rate and propagation speed of retinal waves, as assayed by calcium imaging, are sensitive to pharmacological manipulations of spillover and inhibition, demonstrating a role for both signaling pathways in shaping the spatiotemporal properties of glutamatergic retinal waves.