Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors

Abstract

Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process.

Rules for Shaping Neural Connections in the Developing Brain

“…A form of retinal waves have also been described in zebrafish (Zhang et al, 2016). However they do not appear to be present in amphibians, which are able to rely on photoreceptor-driven vision from the onset of development of the retinotectal projection.…”

“…This study revealed that the initiation point of the waves is biased to the ventrotemporal region of the retina, an observation that is particularly interesting in light of the fact that a locomoting fish or tadpole in the wild would typically experience natural visual stimuli as optic flow similarly sweeping from temporal to nasal retina, further arguing that retinal waves may have evolved as a replacement for natural vision prior to eye-opening. Retinal waves in zebrafish also stereotypically originate from the temporal retina (Zhang et al, 2016). In tadpoles, it has been shown directly that visual stimulation which includes optic flow in this more natural direction is far more effective at refining the retinotopic projection of RGCs than an identical amount of stimulation oriented in the opposite direction (Hiramoto and Cline, 2014).…”

“…In zebrafish, only one stage type of retinal waves has been described. They originate at the axonal terminals of bipolar cells and depend mostly on ionotropic glutamatergic receptors and gap junctions, with acetylcholine receptors likely having a modulatory role (Zhang et al, 2016). …”

“…Zhang et al (2016) have shown that retinal waves in zebrafish are restricted to a very short developmental window 2.5–3.5 days post-fertilization (dpf). During this period RGCs begin to form synapses with postsynaptic tectal neurons (2 dpf) and visual behaviors such as prey capture and predator avoidance emerge shortly afterwards (4–6 dpf; Stuermer, 1988; Borla et al, 2002).…”

Investigating the links between spontaneous activity and behaviour in the zebrafish optic tectum

“…This has been postulated to be driven primarily by hardwired molecular cues (Nevin et al, 2008). However, waves of spontaneous activity that propagate across the retina are also thought to play a significant role in this tectal patterning (Zhang et al, 2016). Hence, the relative influence of both evoked retinal input and spontaneous retinal activity on spontaneous activity within the tectum remains unclear.…”