The neural circuit that generates saccades. Saccades are initiated by activity in neurons of the frontal and parietal eye fields of the cerebral cortex. These signals then follow two pathways projecting to the nucleus reticularis tegmenti pontis (NRTP) of the pontine reticular formation and the superior colliculus (SC). The NRTP sends projections to the oculomotor vermis (OMV) (lobules 5-7) of the cerebellar cortex which, in turn, sends GABAergic inhibitory signals to the underlying caudal fastigial nucleus (fastigial oculomotor region [FOR]; gray box is the cerebellum). The FOR projects to the omnidirectional pause neurons (OPN) of the saccadic burst generator area in the nucleus raphe interpositus of the midline pons. Excitatory burst neurons (EBN) and inhibitory burst neurons (IBN) receive inhibitory projections from OPN. The OPN have a key role in maintaining sustained inhibition of the EBN and IBN when steady fixation is required. When a rapid shift of gaze is needed, OPN-triggered inhibition on the EBN and IBN is suddenly removed, causing a rebound increase in the firing rate of these neurons. The EBN project directly to the ipsilateral abducens nucleus (VIth nucleus), where they synapse upon abducens motoneurons (mn) and internuclear neurons (in) (green excitatory projections). The internuclear neurons of the abducens nucleus project to the medial rectus subgroup of the contralateral oculomotor nucleus (IIIrd nucleus) (see green excitatory projections crossing the dashed midline). Hence, for making rightward saccades, the excitatory burst of activity reaches the right abducens and left IIIrd nerve nucleus motoneurons from EBN in the right paramedian pontine reticular formation (PPRF). The right side (ipsilateral) IBN, which receives inhibitory inputs from OPN and the left (contralateral) IBN, projects to the contralateral (left) abducens nucleus, inhibiting the abducens motoneurons that innervate the antagonistic muscles.

The saccade generator. A. The premotor network. The excitatory burst neurons (EBN) and inhibitory burst neurons (IBN) send local feedback projections that implement reciprocal inhibition for generating accurate and high-velocity saccades. OPN, omnipause neurons; yellow box: feedback gain. B. The model burst neuron membrane. The short latency negative feedback loop is schematized as a blue arrow with a yellow box. This loop is around a high-gain (k) amplifier built into the burst neurons. Although the gain of the negative feedback loop around the burst neuron circuit determines the amplitude of the saccade, the delay time is not the main determinant of the frequency of saccadic oscillations. (Red lines indicate inhibitory projections. Green lines indicate excitatory projections. The blue line indicates feedback projection.)

The influence of currents on the strength of postinhibitory rebound (PIR). A. Schematic diagram of the normal physiologic state. I_h is a pacemaker conductance activated by a hyperpolarizing membrane potential (in the figure, I_h activates below membrane threshold). This inward cationic conductance further depolarizes the membrane. Notice the direction of the arrow in the figure. At approximately 60 mV membrane potential, I_h gradually ceases and I_T begins to activate. I_T further depolarizes the membrane until a sodium conductance (I_Na) mediates a burst of action potential spikes. This burst of spikes characterizes normal PIR. B. Schematic diagram of the state when I_h or I_T increases beyond physiologic limits. As I_h and/or I_T increase, the membrane depolarizes faster. Notice thicker arrows in this panel and a steeper slope of the membrane potential compared with the gray line in A. In this situation, action potential spikes are also more frequent and thus PIR is stronger. C. Illustration of a state when I_h and/or I_T are decreased below their physiologic limits When I_h and/or I_T are weaker, the rate of membrane potential depolarization is relatively slower. Compare the shallower slope of membrane depolarization to the gray line in C. Hence the action potential spikes are less frequent, reflecting a weaker PIR. Black traces represent membrane potential. Lower arrows represent hyperpolarization activated inward cation currents (I_h). Upper arrows are low threshold calcium currents (I_T). The dashed line represents the membrane threshold.

Oscillation kinematics and simulated parameters determining membrane properties. Model parameters such as membrane time constant (mTc) and burst neuron gain influence the frequency (A) and amplitude (B) of simulated saccadic oscillations. Values of simulated frequency and amplitude are color-coded. Burst neuron gain and mTC determine oscillation frequency. Burst neuron gain predominantly determines oscillation amplitude.