The Oscillatory Potentials

The oscillatory potentials (OPs) are a series o f up to seven rhythmic wavelets superimposed on the rising phase of the b-wave. They were first reported by Granit and Munsterhjelm

{1937) in the frog ERG, but it was not until 1953 that similar wavelets were observed in the

human ERG {Cobb and Morton, 1953). The OPs have a higher dominant frequency (90-160 Hz) than the a- and b-waves, which are dominated by components at a frequency o f around 25 Hz {Algvere and Wachtmeister, 1972). When the ERG is recorded with standard high- and low- bandpass frequency filters the OPs are difficult to discern, but judicial filtering can be used to isolate them effectively from the lower frequency components. The International Society for the Clinical Electrophysiology o f Vision (ISCEV) standard suggests bandpass filtering o f lOO-lOOOHz {Marmor & Zrenner, 1999).

Optimal recording o f the OPs requires specific adaptalional conditions. The OPs have been shown to reflect both photopic and scotopic activity {Wachtmeister et al, 1974), and thus mesopic conditions are found to be the most effective in eliciting OPs. Such conditions are best obtained by a period o f total dark adaptation, followed by a ‘conditioning’ flash

{Wachtmeister, 1973).

The origin o f these responses has been the source o f some contention. Both rod and cone systems are known to contribute to the OPs {Peachey et al, 1987), but there is uncertainty regarding the precise retinal generators. Current source density profiles have indicated that OPs originate from a proximal locus i.e. the inner plexiform layer {Ogden, 1973;

Wachtmeister & Dowling, 1978; Heynen et al, 1985). The proximal retinal origin is further

indicated by the suppression of OPs in cases o f experimental {Brown, 1968) and pathologic

{Yonemura et al, 1962) central retinal artery occlusion.

Chapter 4 Ocular Electrophysiology

amacrine cells, are involved in the generation o f the early OPs. The later OPs are also affected by these drugs, but to a lesser extent (Gutierrez & Spiguel, 1973; Hempel, 1972; Wachtmeister & Dowling, 1978, Wachtmeister, 1981; Pourcho, 1996). Other studies have

found the application o f GABA antagonists to result in a substantial reduction or abolition of the early OPs ( Wachtmeister, 1980). GABA is an amino acid, which is also part o f the negative feedback process at the level o f the amacrine cells (Burchartd, 1972; Nakamura et

al, 1979) and interplexiform cells (Nakamura et al, 1980).

The later OPs are reduced by the glycine antagonist strychnine (Wachtmeister, 1980). Glycine is an inhibitory neurotransmitter which is only found in the inner plexiform layer of the retina, and is involved in the processing o f the OFF-pathway, mediated by hyperpolarising bipolars

(Cunningham and Miller, 1980). The earlier OPs therefore seem be related to the rod-

mediated GABA-nergic ON-pathway, and the later ones to the glycine sensitive OFF- pathway. The last OP has been found to be consistently time-locked to stimulus offset, supporting this supposition (Kojima & Zrenner, 1978). The possible rod-mediated origin o f the earlier OPs (OP2 and OP3) has been further supported by studies demonstrating a selective reduction in the amplitude o f these peaks when the eye is stimulated by light flickering at a frequencies too fast for the rod system to process (Lachapelle et al, 1983). Other reports have suggested that OP3 and OP4 are rod dominated. Janaky et al (1996), for example, used blue flashes against a dark background to elicit rod mediated OPs, and found that they corresponded well with OPs 3 and 4 recorded in response to a standard white flash. It has also been noted that retinopathies resulting in a differential dysfunction in the rod system lead to a decrease in the amplitude o f the earlier OPs, whilst it is the later OPs which are principally affected by loss of cone function (Wachtmeister, 1998).

Further evidence suggesting distinct retinal origins for the OPs comes from depth profile studies (Wachtmeister and Dowling, 1978). The first OP appears to have the most proximal origin, while the second and third are localised more distally, and the fourth and fifth are located in the outer lamina o f the inner plexiform layer. These findings are consistent with the theory that OPs are generated by a series o f inhibitory feedback systems operating at different levels within the retina (Brown, 1968).

Pharmacological studies have also suggested that OPs reflect the activity o f the inhibitory feed-back circuits within the inner retina, driven by amacrine, and possibly interplexiform cells (Wachtmeister, 1998). This is further supported by intracellular recordings from amacrine (Marchiafava & Weiler, 1982) and interplexiform cells (Hashimoto et al, 1980),

Chapter 4 Ocular Electrophysiology

which demonstrate oscillations in their light-evoked responses. The amacrine cells, however, have a tangential orientation, and are thus unlikely to cause a trans-retinal potential. Although this suggests that they do not directly generate the OPs, there is still likely to be some underlying amacrine involvement ( Wachtmeister, 1998). Interplexiform cells, which form both pre- and post- synaptic connections with amacrine cells, are more radial in orientation than amacrines (Boycott et al, 1975), and may be implicated in OP generation.

Evidence against ganglion cells being directly involved in the generation of OPs is provided by studies which have demonstrated that OPs are not affected in patients with optic nerve atrophy ( Wanger & Persson, 1983; Wachtmeister & el Azazi, 1985). Furthermore, pharmacological investigation has shown that the administration of tetradoxin, which blocks ganglion cell action potentials, has a minimal effect on primate OPs {Ogden, 1973). However, other studies report a reduction in OP amplitude in patients with glaucoma or optic nerve diseases {Gur et al, 1987; Vaegan et al, 1995). The extent o f any involvement of the ganglion cells in the generation of the OPs is as yet uncertain, but would seem to be small.