In a recent study, Dr. DU Jiulin’s lab at Institute of Neuroscience (ION), Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences, found that glutamatergic retinal waves are initiated at the axon terminal of bipolar cells through a N-methyl-D-aspartate subtype of glutamate (NMDA) autoreceptor-dependent self-amplifying mechanism. This work was published online in Nature Communications entitled “Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors”.

In early development, spontaneous patterned neural activities exhibit wave-like propagation among neighboring retinal ganglion cells (RGCs), called retinal waves. After nearly three decades’ intensive investigation, it has been known that retinal waves can propagate via the optic nerve to the central visual system, and guide the activity-dependent refinement of visual topographic maps. In terms of mechanisms underlying their generation, it is known that the excitatory drive of retinal waves switches from cholinergic to glutamatergic during development. Cholinergic waves are triggered by starburst amacrine cells. However, the origin and underlying mechanism of glutamatergic retinal waves are still a mystery.

To investigate the origin of glutamatergic waves, researchers first performed in vivo time-lapse two-photon calcium imaging in zebrafish larvae to monitor neuronal activities among the populations of bipolar cells (BCs), the primary excitatory presynaptic source of RGCs. They discovered for the first time that BCs themselves display glutamatergic retinal waves. 

To further explore the involved mechanism, the researchers combined in vivo whole-cell patch-clamp recording, optogenetics, glutamate uncaging, and glutamate imaging, and demonstrated that BC waves are initiated at the BC ATs through a NMDA autoreceptor-dependent mechanism.

Furthermore, the researchers found that BC waves can propagate to downstream RGCs and optic tectum (OT), the recipient of RGC axons, suggesting that glutamatergic waves previously observed in RGCs and OTs are actually a mirror of BC waves. In contrast to previous in vitro studies that showed a random pattern of retinal wave initiation, this in vivo work unexpectedly reveals that the temporal retina has the lowest threshold for wave initiation, though each region of the retina is capable of generating waves.

This property results in the preferential initiation of retinal waves at the temporal retina, which may be the reason for more synaptic connections in this region and higher visual acuity for frontal environment.

Taken together, this study discovers that the ATs of BCs initiate glutamatergic retinal waves through a NMDA autoreceptor-dependent mechanism.

This work was mainly carried out by Dr. ZHANG Rongwei under the supervision of Dr. DU Jiulin at Institute of Neuroscience, in collaboration with Dr. Koichi Kawakami’s group at National Institute of Genetics, Japan.

The study was supported by grants of the Strategic Priority Research Program from Chinese Academy of Sciences, “973” Programs from Ministry of Science and Technology of China, the National Outstanding Young Scientist Program from National Science Foundation of China, etc.