Search

In congenital stationary night blindness, type 2 (CSNB2)-a disorder involving the Ca v 1.4 (L-type) Ca 2+ channel-visual impairment is mild considering that Ca v 1.4 mediates synaptic release from rod and cone photoreceptors. Here, we addressed this conundrum using a Ca v 1.4 knockout (KO) mouse and a knock-in (G369i KI) mouse expressing a non-conducting Ca v 1.4. Surprisingly, Ca v 3 (T-type) Ca 2+ currents were detected in cones of G369i KI mice and Ca v 1.4 KO mice but not in cones of wild-type mouse, ground squirrels, and macaque retina. Whereas Ca v 1.4 KO mice are blind, G369i KI mice exhibit normal photopic (i.e. cone-mediated) visual behavior. Cone synapses, which fail to form in Ca v 1.4 KO mice, are present, albeit enlarged, and with some errors in postsynaptic wiring in G369i KI mice. While Ca v 1.4 KO mice lack evidence of cone synaptic responses, electrophysiological recordings in G369i KI mice revealed nominal transmission from cones to horizontal cells and bipolar cells. In CSNB2, we propose that Ca v 3 channels maintain cone synaptic output provided that the nonconducting role of Ca v 1.4 in cone synaptogenesis remains intact. Our findings reveal an unexpected form of homeostatic plasticity that relies on a non-canonical role of an ion channel., Competing Interests: JM, GO, Jd, AH, CG, SW, KR, DF, NS, DM, BZ, SD, MH, AL No competing interests declared, (© 2024, Maddox, Ordemann et al.)

Output signals of neural circuits, including the retina, are shaped by a combination of excitatory and inhibitory signals. Inhibitory signals can act presynaptically on axon terminals to control neurotransmitter release and regulate circuit function. However, it has been difficult to study the role of presynaptic inhibition in most neural circuits due to lack of cell type-specific and receptor type-specific perturbations. In this study, we used a transgenic approach to selectively eliminate GABA A inhibitory receptors from select types of second-order neurons - bipolar cells - in mouse retina and examined how this affects the light response properties of the well-characterized ON alpha ganglion cell retinal circuit. Selective loss of GABA A receptor-mediated presynaptic inhibition causes an enhanced sensitivity and slower kinetics of light-evoked responses from ON alpha ganglion cells thus highlighting the role of presynaptic inhibition in gain control and temporal filtering of sensory signals in a key neural circuit in the mammalian retina., Competing Interests: JN, BE, MH, RS No competing interests declared, (© 2021, Nagy et al.)

Synapses are fundamental information processing units that rely on voltage-gated Ca 2+ (Ca v ) channels to trigger Ca 2+ -dependent neurotransmitter release. Ca v channels also play Ca 2+ -independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Ca v 1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Ca v 1.4, we report that the Ca v 1.4 protein, but not its Ca 2+ conductance, is required for the molecular assembly of rod synapses; however, Ca v 1.4 Ca 2+ signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Ca v channels serve both as organizers of synaptic building blocks and as sources of Ca 2+ ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system., Competing Interests: JM, KR, RY, BW, JH, PD, VK, LD, SB, NA, MH, AL No competing interests declared, (© 2020, Maddox et al.)