II. Photoreceptors to Bipolar Cells

Inside the retina of a mammal, the neurons communicate chemically with a host of different neurotransmitter substances. I'll mention three main types in our discussions. First is the prototypical ‘excitatory’ type, glutamate, which you'll encounter most when learning about communication in the retina. The other two are gamma-Aminobutyric acid (GABA) and glycine, both of which are ‘inhibitory’.

These substances are released at the synapse, the functional interface between two neurons. A neurotransmitter is a ligand, and as such only one half of a communication system. The other half is the receptor. It’s really the receptor that determines the intricacies of a cell’s response to a given ligand. The nature of a receptor can make even a classically excitatory neurotransmitter, like glutamate, produce an inhibitory response.

Photoreceptor cells release glutamate into the extracellular space in the retina known as the outer plexiform layer (OPL). In it lie the receiving processes of retinal bipolar cells - ‘relay’ cells that gather and pass on the electrical message. Horizontal cells, which gather and integrate input from a range of photoreceptors stretching laterally across the retina, also figure in the OPL and are discussed more in the next section.

A bipolar cell is so named because it has two processes emanating from its cell body. In the retina, one process winds its way into the OPL, where it may connect to a photoreceptor or to a horizontal cell, or to both at the same time. The other process extends in the opposite, inward direction, synapsing onto a retinal ganglion cell (RGC) or amacrine cell in the inner plexiform layer (IPL). Some of these bipolar cells, termed H (hyperpolarizing) bipolar cells, are found to be non-responsive to light, firing in darkness. D (depolarizing) bipolar cells, on the other hand, fire under a light stimulus and are shut down by darkness.

There are at least 10 different types of cone bipolar cells, but only one rod bipolar cell type. It's been hypothesized that this difference is due to the relatively later evolution of rod photoreceptors compared to cones. This just means that the latter type of photoreceptor may appear in more flavors in part because it's had more time to change.

The H bipolar responds positively to the glutamate released by photoreceptor cells in darkness. It is said to be ‘sign-conserving’ because it propagates the excitatory signal glutamate imparts upon it. It’s able to do this because the glutamate receptor it expresses on its postsynaptic terminal is ionotropic. When such a receptor is bound to its ligand (glutamate in this case), it opens and allows positively charged ions to flow into and depolarize the cell.

D bipolar cells, on the other hand, contain metabotropic glutamate receptors. The ‘meta-’ part of the name indicates that they use a metabolic pathway to function. A metabolic pathway is one which starts with reactants, and, using a series of enzymes, modifies them to end up with the products it needs. The products generally still affect ion channels. Though the end target is the same, the process to reach it is indirect and allows for more subtle responses.

The metabotropic receptor that D bipolar cells employ is called mGluR6. When this receptor binds glutamate - when the eye is in darkness - it sets off an intracellular signalling cascade whose end products act by closing down cGMP-gated Na+ channels, in a very similar process to that discussed in phototransduction. When glutamate is absent, on the other hand, the channels remain open and the cell depolarizes. Since it reverses the classical depolarizing influence of glutamate, the mGluR6 receptor is known as ‘sign-inverting’. All rod bipolar cells exhibit this receptor type, which means these cells are in a state of constant suppression throughout the day, as long as your eye has light entering it.

Like photoreceptors, bipolar cells in the retina are small enough to use graded potentials rather than action potentials to communicate. This mechanism allows for a refined, sensitive signal. It’s also important to note that a single photoreceptor can be connected to either a H or a D bipolar cell, or both at the same time.

I'll end this section with a few details. A rod bipolar is typically supplied by 15-45 photoreceptors. Some cone bipolars, those located above cones in the fovea of the retina, are connected to only one cone each. Other cone bipolars can get a mix of inputs. Like many parts of the human nervous system, simple rules hold only loosely in the eye.