Bipolar Cell Pathways in the Vertebrate Retina by Ralph …

Ralph Nelson and Victoria Connaughton

1. Introduction.

Retinal ganglion cells are typically only two synapses distant from retinal photoreceptors, yet ganglion cell responses are far more diverse than those of photoreceptors. The most direct pathway from photoreceptors to ganglion cells is through retinal bipolar cells. Thus, it is of great interest to understand how bipolar cells transform visual signals.

Werblin and Dowling (1) were among the first to investigate light-evoked responses of retinal bipolar cells. Based on these studies using penetrating microelectrodes, they proposed that retinal bipolar cells lacked impulse activity, and that they processed visual signals through integration of analogue signals, that is synaptic currents and non-spike-generating voltage-gated membrane currents.

Frank Werblin and John Dowling discovered the ON or OFF light-evoked physiology of retinal bipolar cells (1). They characterized these neurons as processors of analogue visual signals that did not use impulse generation. The work was done at Johns Hopkins University as a part of Frank Werblins doctoral dissertation under John Dowlings mentorship.

Werblin and Dowing also proposed that retinal bipolar cells come in two fundamental varieties: ON-center and OFF-center (Fig. 1). Both types displayed a surround region in their receptive field that opposed the center, similar to the classic, antagonistic center-surround organization earlier described for ganglion-cell receptive fields (2). Ganglion cell receptive field organization is further reviewed in the Webvision chapter on ganglion cells. ON-center bipolar cells are depolarized by small spot stimuli positioned in the receptive field center. OFF-center bipolar cells are hyperpolarized by the same stimuli. Both types are repolarized by light stimulation of the peripheral receptive field outside the center (Fig. 1). Bipolar cells with ON-OFF responses were not encountered (1). ON-OFF responses, excitation at both stimulus onset and offset, first occur among amacrine cells, neurons postsynaptic to bipolar cells.

The Werblin and Dowling characterization of bipolar-cell physiology has proved quite durable over many decades. The notion that bipolar cells do not spike has found exception for some bipolar types. Dark-adapted Mb1 (rod bipolar cells) of goldfish generate light-evoked calcium spikes. These spikes originate in bipolar-cell axon terminals (3, 4). Through genetic imaging techniques this finding has been extended to the axon terminals of many zebrafish bipolar-cell types. In these studies bipolar terminals were labeled transgenically with the Ca2+ reporter protein SyGCaMP2 and light-induced fluctuations in Ca2+ were followed by 2-photon photometry. Fully 65% of the terminals delivered a spiking Ca2+ signal (4). In the cb5b bipolar-cell type of ground squirrel retina Na+ action potentials are driven by light. Other bipolar types in this retina do not exhibit spiking (5). These results suggest that bipolar cells are responsible for significantly more of the encoding of visual signals than had been previously supposed, and that axon-terminal spiking is actively involved. Impulse generation in bipolar cells is further discussed in the section on Voltage-gated currents.

See the article here:
Bipolar Cell Pathways in the Vertebrate Retina by Ralph ...