The role of omnipause neurons: why glycine?

The anatomy and neurophysiology of the saccadic eye movement system have been well studied, but the roles of certain key neurons in this system are not fully appreciated. Important clues about the functional interactions in the saccadic system can be gleaned from the histochemistry of different saccadic neurons. The most prominent inhibitory neurons in the circuit are the omnidirectional pause neurons (OPN), which inhibit the premotor burst neurons that drive the eye. Most inhibitory neurons in the brain transmit gamma-aminobutyric acid (GABA), but OPN transmit glycine (Gly). It is interesting to ask whether the saccadic system would work any differently if OPN were GABA-ergic. Gly and GABA receptors both provide a channel for a hyperpolarizing Cl(-) current that inhibits its target neuron. Depolarizing currents that excite the neurons come through several channels, including the NMDA receptor (NMDAR). The NMDAR is unique among receptors in that it has active sites for two different neurotransmitters, glutamate (Glu) and Gly. Gly is a co-agonist that acts to amplify the current produced by Glu. We have proposed a model of the saccadic brain stem circuitry that exploits this dual role of Gly to produce both inhibition of the saccadic circuit during fixation, and to increase its responsiveness, or gain, during movements. This suggests that OPNs act more as a regulator of the saccadic circuit's gain, rather than as a gate for allowing saccades. We propose a new hypothesis: the OPNs play a general role as a modulator of arousal in orienting subsystems, such as saccades, pursuit, head movements, etc.