Early afferent signaling in the outer plexiform layer regulates development of horizontal cell morphology

Abstract

The dendritic patterning of retinal horizontal cells has been shown to be specified by the cone photoreceptor afferents. The present investigation has addressed whether this specification is due to visually dependent synaptic transmission in the outer plexiform layer or to some other early, pre-visual, neural activity. Individually labeled horizontal cells from dark-reared mice, as well as from mice carrying a mutation in the Cacna1f gene, which encodes the pore-forming calcium channel subunit Ca(v)1.4, were assessed for various morphological features. The dark-reared mice showed no alteration in any of these features, despite showing a compromised maximal voltage response in the electroretinograms. The retinas of Cacna1f mutant mice, by contrast, showed conspicuous morphological changes that mimicked the effects observed previously in coneless transgenic mice. These changes were present as early as postnatal day 10, when the shape and density of the cone pedicles appeared normal. Ultrastructurally, however, the pedicles at this early stage, as well as in maturity, lacked synaptic ribbons and the invaginations associated with postsynaptic processes. These results suggest a role for this calcium channel subunit in ribbon assembly in addition to its role in modulating calcium influx and glutamate release. Together, they suggest a complex cascade of interactions between developing cone pedicles and horizontal cell dendrites involving early spontaneous activity, dendritic attraction, ribbon assembly, and pedicle invagination.

Cannabinoid receptor type 1 expression during postnatal development of the rat retina

“…In support of this assumption, cone photoreceptors are known to modulate the organization of horizontal cell dendritic trees through early glutamatergic activation (starting around P2; Raven et al, 2008). Also, endocannabinoids synthesis is known to be activity dependent (see Freund et al, 2003 for review), and CB1R was shown to negatively modulate glutamatergic release from cones in goldfish retina through retrograde signaling (Fan and Yazulla, 2007).…”

Functional architecture of the retina: Development and disease

“…When excitatory transmission from photoreceptor terminals is perturbed, rod bipolar cell dendrites and horizontal cell processes sprout into the ONL (Dick et al, 2003; Raven et al, 2008). Surprisingly, sprouting of bipolar cell dendrites does not occur when postsynaptic bipolar cell function is perturbed as in mice lacking the metabotropic glutamate receptor mGluR6 (Masu et al, 1995) or when the signaling cascade downstream from these receptors is disrupted (Dhingra et al, 2000; Koike et al, 2010).…”

Illuminating the Multifaceted Roles of Neurotransmission in Shaping Neuronal Circuitry

“…A common finding in Cacna1f mutants and CNGA3/CNGB1 double knockout (dKO) mice is the sprouting of postsynaptic processes and the retraction of rod axon terminals into the outer nuclear layer (ONL) (Bayley and Morgans, 2007; Chang et al, 2006; Mansergh et al, 2005; Michalakis et al, 2013; Raven et al, 2008; Regus-Leidig et al, 2014; Zabouri and Haverkamp, 2013). In Ca V 1.4(α1F) KO mice, cone photoreceptor axons also show abnormal branching, including elaboration of several primary processes from the cell body.…”

“…Thus, proper transmission from photoreceptors is necessary to maintain the laminated organization of the outer synaptic layer (Figure 6A, B). However, dark-rearing does not induce sprouting, indicating that light-driven activity may not be critical for restraining processes of the bipolar and horizontal cells to the outer plexiform layer (OPL) (Dunn et al, 2013; Raven et al, 2008). Another finding common to transmission mutants is that cone bipolar cells examined thus far are less susceptible to dendritic sprouting.…”

“…In the mGluR6 loss of function mutant (nob4), horizontal cell processes invaginate the rod photoreceptor, but bipolar cell dendrites do not (Cao et al, 2009). For photoreceptor terminals located at the OPL or at ectopic locations in the Cacna1f mutant, both horizontal and bipolar cell processes fail to invaginate the photoreceptor pedicle from early stages of development onwards (Raven et al, 2008; Regus-Leidig et al, 2014; Zabouri and Haverkamp, 2013). Moreover, ribbons are abnormally shaped and unanchored in the Cacna1f mutant (Bayley and Morgans, 2007; Raven et al, 2008; Regus-Leidig et al, 2014; Zabouri and Haverkamp, 2013).…”