The Inner Plexiform Layer

The inner plexiform layer is where synapses occur between bipolar cell axons and ganglion cell dendrites. Invaginating synapses of depolarising ON- bipolars are found in the inner part of the inner plexiform layer. Rod bipolars also synapse in this part of the inner plexiform layer. The flat synapses o f hyperpolarising OFF- bipolars are found in the outer part o f the layer. Amacrine cells also have their processes in the inner plexiform layer, forming contacts with bipolar cells, other amacrine cells, interplexiform cells and ganglion cells {Dowling,

1966).

Specialised ribbon synapses in the inner plexiform layer connect a bipolar axon, an amacrine cell process, and a ganglion dendrite {Dowling, 1966). A reciprocal synapse is also made between a second terminal of the amacrine cell, and the bipolar axon, providing a negative feedback loop {Park, 1994).

2.9.1 Amacrine Cells

The term ‘amacrine’ was used by Cajal {1892), to describe a group of intemeurones which lack an axon, but which have a complex dendritic tree in the inner plexiform layer. Their role lies in the integration and modulation o f the neural signal presented to the ganglion cells. The majority o f amacrine cells have their cell bodies in the inner nuclear layer. A significant minority, however, which may comprise up to 20% o f the total population, have cell bodies in the ganglion cell layer {Wassle et al, 1987). These are known as displaced amacrine cells. At least 25 amacrine cell types have already been identified in the human retina {Mariani,

1990; Kolb et al, 1992). Diversity in appearance and physiology of these sub-types o f

amacrine cells appears to reflect a wide range o f functions. One example o f this is the group of somatostatin-immunoreactive amacrine cells {Rickman & Brecha, 1989). These have dendrites and cell bodies in the lower retina, whilst their axons extend into the upper retina. Somatostatin has been found to render ganglion cells more responsive to light {Zalutsky <£

Chapter 2 The Retina

modulation o f retinal function to allow for differences in the ambient illumination of the upper and lower areas of the retina.

Amacrine cells are classified according to dendritic tree size and branching characteristics, according to neurotransmitters released at chemical synapses, and also according to the stratification of their dendrites in the inner plexiform layer (Mariani, 1990; Kolb et al, 1992). Cajal (1892) arbitrarily subdivided the inner plexiform layer into 5 strata in the classification of amacrine cells. Neurones terminating in different strata are unable to form synapses with each other, and therefore certain information regarding the function and circuitry of the amacrine cell types may be derived from the location of their end processes within the inner plexiform layer. Amacrine cells whose dendritic processes are solely confined to one stratum are said to be stratified, whilst those whose dendritic trees span all 5 strata are said to be diffuse types. Cajal’s 5 strata have also been grouped into 2 sublamina, according to the nature o f synapses made within those layers. Strata 1 and 2 comprise sublamina a, which contains bipolar cell axons, and ganglion cell dendrites which make connections with OFF- centre ganglion cells, whilst strata 3, 4 and 5 make up sublamina b, which is the ON- stratum of the inner plexiform layer (Famiglietti & Kolb, 1976).

The amacrine cells utilise a wide range of neurotransmitters in their chemical synapses. These may be excitatory, although the majority of amacrine cells in vertebrates form inhibitory synapses. Nearly half o f amacrine cells use the inhibitory amino acid glycine. All glycinergic amacrine cells have diffuse dendritic fields. This means that they have dendritic terminals in multiple strata o f the inner plexiform layer, and can thus communicate with all bipolar types. One well-characterised small-field glycinergic amacrine cell, found in almost all mammals, is All (Boycott & Dowling, 1969). All has its major input from rod bipolar axons in sublamina b, although it also has a smaller input from OFF-centre bipolar cells in sublamina a (Strettoi et

al, 1992). The major output of the All amacrine cell is to OFF-centre ganglion cell dendrites

in sublamina a (Famiglietti & Kolb, 1975; Kolb & Nelson, 1993), although they also synapse via gap junctions with cone bipolar cells which then make connections with ON-centre ganglion cells in sublamina b. Diffuse cells such as All are therefore able to integrate information from ON-, OFF- and rod pathways.

In contrast, cholinergic amacrine cells have stratified dendritic trees. It appears that about half of cholinergic amacrine cells have cell bodies in the ganglion cell layer, and stratify in the inner layer of the inner plexiform layer, forming contacts with ON- cells. The other half o f the

Chapter 2 Ihe Retina

cells have cell bodies in the inner nuclear layer, and stratify in the outer region o f the inner plexiform layer, synapsing with OFF- cells {Hayden et al, 1980; Bloomfield & Miller, 1986). These cholinergic cells have been found to release both acetyl choline and GABA at synapses

{O'Malley <£ Masland, 1989), i.e. they release both excitatory and inhibitory

neurotransmitters. It is thought that this characteristic may help to determine the directional sensitivity o f the ganglion cells with which the cholinergic amacrines synapse {Masland &

Ames, 1976; Ariel & Daw, 1982).

GABA-ergic amacrine cells constitute 30% of the total amacrine cell population, and the majority o f the displaced amacrine cells. An example of a GABA-ergic type of amacrine cell is A 17. This cell forms a key part o f the rod circuitry, and is the second most common type o f amacrine cell in the retina. It is reciprocal to the rod bipolar cell, providing a negative feedback loop.

In addition, smaller numbers o f amacrine cells have been found to incorporate dopamine

{Pourcho, 1996), seratonin {Vaney, 1986), and somatostatin {Pourcho, 1996) as their

neurotransmitters.

2.9.2 Interplexiform Cells

The interplexiform cell is an interneurone, which has processes extending into both the inner and outer plexiform layers. It appears from electron microscopy studies that interplexiform cells form GABA-ergic synapses in the inner plexiform layer with a type o f amacrine cell, as yet unclassified, as well as with rod and cone bipolar cells. In the inner nuclear layer and outer plexiform layer the cells make connections with rod and cone bipolar cell bodies and dendrites {Kolb & West, 1977; Nakamura et al, 1980, Lindberg & Fisher, 1986). There is also evidence that processes from the interplexiform cells contact cone pedicles via specialised gap junctions {Lindberg & Fisher, 1986).

The interplexiform cell appears to provide feedback to the photoreceptors from the inner retinal layers {Kolb et al, 1992).