CaV3.2 KO mice have altered retinal waves but normal direction selectivity

Abstract

Early in development, before the onset of vision, the retina establishes direction-selective responses. During this time period, the retina spontaneously generates bursts of action potentials that propagate across its extent. The precise spatial and temporal properties of these “retinal waves” have been implicated in the formation of retinal projections to the brain. However their role in the development of direction selective circuits within the retina has not yet been determined. We addressed this issue by combining multi-electrode array and cell-attached recordings to examine mice that lack the CaV3.2 subunit of T-type Ca2+ channels (CaV3.2 KO) because these mice exhibit disrupted waves during the period that direction selective circuits are established. We found that the spontaneous activity of these mice displays wave-associated bursts of action potentials that are altered from control mice: the frequency of these bursts is significantly decreased and the firing rate within each burst is reduced. Moreover, the retina’s projection patterns demonstrate decreased eye-specific segregation in the dLGN. However, after eye-opening, the direction selective responses of CaV3.2 KO DSGCs are indistinguishable from those of wild-type DSGCs. Our data indicate that, although the temporal properties of the action potential bursts associated with retinal waves are important for activity-dependent refining of retinal projections to central targets, they are not critical for establishing direction selectivity in the retina.

Stimulus-dependent recruitment of lateral inhibition underlies retinal direction selectivity

“…We cannot discount the possibility that developmental compensation has occurred at sites not examined in this study. However, our findings are consistent with multiple previous studies that demonstrate that the early development of retinal direction selectivity is highly resistant to changes in neural activity (Chan and Chiao, 2008; Elstrott et al, 2008; Hamby et al, 2015; Sun et al, 2011; Wei et al, 2011). …”

“…Although multiple studies have demonstrated that the emergence of retinal direction selectivity occurs independent of neural activity (Elstrott et al, 2008; Hamby et al, 2015; Sun et al, 2011; Wei et al, 2011), we needed to rule out potential developmental changes in this circuit in Gabra2 KO mice. Therefore, we examined other critical synapses involved in direction selectivity: the GABAergic and cholinergic synapses between SACs and DSGCs.…”

Light Prior to Eye Opening Promotes Retinal Waves and Eye-Specific Segregation

“…We observed a reduction in eye-specific segregation induced by dark-rearing prior to eye-opening (Figure 4). The magnitude of this reduction is comparable to several other manipulations that disrupt eye-specific segregation (Kirkby et al, 2013), including interference with the complement cascade [for example, see (Bialas and Stevens, 2013)], targeted killing of ipRGCs (Chew et al, 2017), and disruption of glutamatergic waves (Blankenship et al, 2011; Hamby et al, 2015; Xu et al, 2010). Interestingly, we found that retinal projections to non-image-forming parts of the brain—the vLGN and OPN—undergo developmental eye-specific refinement, but not in a light-dependent manner (Figure S3).…”

Activity-dependent development of visual receptive fields

“…CaV3.2 knockout mice exhibit disrupted waves during the period that direction selective circuits are established, from P11–P14, however, after eye-opening their direction selective ganglion cells (DSGCs) are indistinguishable from wild type mice 18 . Development of the retina’s direction selective circuits depends on an asymmetry in synapse number between inhibitory starburst amacrine cells (SACs) and DSGCs 19 , a circuit that emerges in an activity-independent manner 20 .…”