Light Evokes Ca 2+ Spikes in the Axon Terminal of a Retinal Bipolar Cell

Abstract

Bipolar cells in the vertebrate retina have been characterized as nonspiking interneurons. Using patch-clamp recordings from goldfish retinal slices, we find, however, that the morphologically well-defined Mb1 bipolar cell is capable of generating spikes. Surprisingly, in dark-adapted retina, spikes were reliably evoked by light flashes and had a long (1-2 s) refractory period. In light-adapted retina, most Mb1 cells did not spike. However, an L-type Ca2+ channel agonist could induce periodic spiking in these cells. Spikes were determined to be Ca2+ action potentials triggered at the axon terminal and were abolished by 2-amino-4-phosphonobutyric acid (APB), an agonist that mimics glutamate. Signaling via spikes in a specific class of bipolar cells may serve to accelerate and amplify small photo-receptor signals, thereby securing the synaptic transmission of dim and rapidly changing visual input.

Calcium spike-mediated digital signaling increases glutamate output at the visual threshold of retinal bipolar cells

“…4D as red and green circles, respectively). In these two cells, accordingly, the stationary membrane depolarization in The input resistance of the dark-adapted Mbs was 365 Ϯ 140 M⍀ (n ϭ 55), similar to ϳ444 M⍀ measured at the soma by Protti et al (2000). Red and green circles represent Mbs selected for further analysis shown in E. E: mean response (n ϭ 20) to a current step (42 pA) of 2 Mbs with the same input resistance but generating different maximum light-evoked V m transients: 22.5 mV (red) and 1.54 mV (green).…”

“…Importantly, in the vertebrate retina every BC expresses voltage-gated Ca 2ϩ channels that are essential for glutamate release, but so far only a few types of BCs, in fish and mouse retinas, have been shown to generate light-evoked Ca 2ϩ spikes (Baden et al , 2013aDreosti et al 2011). When present, Ca 2ϩ spikes in BCs originate at the site of presynaptic glutamate release Burrone and Lagnado 1997;Dreosti et al 2011;Palmer 2006;Protti et al 2000), which implicates a potential role for Ca 2ϩ spike-coded digital signaling in mediating BC output (Zenisek and Matthews 1998).…”

“…Less is understood concerning the role of Ca 2ϩ spike-mediated digital BC signaling. In Mb-type BCs that lack voltage-gated Na ϩ currents (Zenisek et al 2001), Ca 2ϩ spikes promote larger and faster somatic light responses (Protti et al 2000), suggesting similar roles for Ca 2ϩ and Na ϩ spikes in BCs (Baden et al 2013b). Importantly, in the vertebrate retina every BC expresses voltage-gated Ca 2ϩ channels that are essential for glutamate release, but so far only a few types of BCs, in fish and mouse retinas, have been shown to generate light-evoked Ca 2ϩ spikes (Baden et al , 2013aDreosti et al 2011).…”

“…To investigate this notion, we sought to measure lightevoked glutamate release from ON-type Mb BCs, which have been shown to produce both Ca 2ϩ spikes and graded potentials upon light stimulation of the retina Joselevich and Kamermans 2007;Protti et al 2000;Saito et al 1979). Furthermore, Mb axon terminals are large enough for direct measurement of exocytosis-associated increases in their membrane capacitance (C m ) with high fidelity (von Gersdorff and Matthews 1999).…”

Two types of cone bipolar cells express voltage-gated Na+ channels in the rat retina

“…Light evoked spike firing has been previously demonstrated in Mb1 bipolar cells in goldfish (Protti et al, 2000). The spiking signal in bipolar cells of goldfish has been proposed to secure the synaptic transmission of dim and rapidly changing visual input (Protti et al, 2000).…”