Correlated discharge among cell pairs within the oculomotor horizontal velocity-to-position integrator

Abstract

In the oculomotor system, temporal integration of velocity commands into position signals may depend on synaptic feedback among neurons of a bilateral brainstem cell assembly known as the "neural integrator." Both ipsilateral excitatory and contralateral inhibitory projections between eye position-related integrator cells are hypothesized as a substrate for positive feedback supporting integration. Presence of feedback interactions should be evident in cross-correlation functions of neuron pairs. Here, unilateral and bilateral paired recordings were obtained during fixation behavior from neurons in goldfish brainstem area I, a key element of the integrator. During fixations, discharge of most unilateral pairs, composed of cells with eye position sensitivities of the same sign, was positively correlated with lag of 0-10 msec (n = 11 of 14 significant). Typically, a very narrow peak (mean half-width <4 msec) near zero lag was observed. Discharge of bilateral pairs, composed of cells with position sensitivities of the opposite sign, was either negatively correlated with lag of 0-10 msec (n = 5 of 13 significant) or not correlated. Troughs in negative correlations always had minima between 3 and 5 msec lag. These results are consistent with the feedback hypothesis of temporal integration, highlighting excitation unilaterally and inhibition bilaterally. Absence of visual input did not weaken correlations, but other sources of correlated input extrinsic to area I were not ruled out. Triplet recordings revealed that unilateral pairwise correlations were primarily independent. Correlation between unilateral pairs systematically decreased with increasing eye position, demonstrating that synchrony is not necessary for persistent activity at high firing rates.

Figure 2.

Cross-correlations of position cells on the same side of midline. A-C, For three different pairs, pair counts from correlations (black) and shuffle-correlations (gray). Vertical dashed lines highlight the position of zero lag. Insets show the average excess correlation relative to baseline at different time lags, measured over distinct 21 bin regions; horizontal line shows the 4σ significance level. In A, the correlation was calculated from (71,356, 104,763) action potentials recorded over 120 min, and the excess correlation was 8.4%. For B, action potential totals, excess, and recording time were (104,708, 91,636), 0.9%, and 125 min, and in C were (98,105, 65,026), 12.6%, and 125 min. Labels in A also apply to B and C.

Figure 3.

Cross-correlations of position cells on the opposite sides of midline. A-C, For three different pairs, pair counts from correlations (black) and shuffle-correlations (gray). Vertical dashed lines highlight the position of zero lag. Insets as in Figure 2. In A, the correlation was calculated from (132,255, 130,913) action potentials recorded over 95 min, and the excess correlation was -5.5%. For B, action potential totals, excess, and recording time were (148,986, 135,264), -12.4%, and 100 min, and in C were (160,274, 42,380), -2.0%, and 120 min. Labels in A also apply to B and C.

Figure 6.

Cross-correlations strength varies with eye position. A-D, Correlations (black) and shuffle-correlations (gray) for data gathered from fixations, in medial to temporal order, at 3.6, 8.5, 16.2, and 19.2° (the rate ranges for the cell with higher threshold were 5-10, 17-18, 27-28, and 40-45 sp/sec, respectively, in A-D). Labels in A and C also apply to B and D. E, Excess pairings as a percentage of baseline for the pair pictured in A-D. Here, data were grouped into bins as described in Materials and Methods. Horizontal bars indicate the range in mean position of fixations in a particular bin. F, Excess pairings from the most temporal (y-axis) and most nasal (x-axis) positions for all ipsilateral pairs.

Figure 1.

Paired recordings of position cells. A, B, Eye position and extracellularly recorded potentials from position neurons on the same (A) and opposite (B) sides of midline. Insets at left are schematized views of the fourth ventricle during recording. FL, Facial lobe; M, midline; Ob, obex; VL, vagal lobe. Scale bar for B is the same as for A.

Figure 4.

Correlation for the population in the light and dark. Excess pair counts, expressed as a percentage relative to baseline, for same-sided cells (unilateral; gray) and opposite-sided cells (bilateral; black). The values in the light are plotted along the abscissa and in the dark along the ordinate. Dashed lines indicate 0 excess.

Figure 5.

Triplet correlation between three position neurons. A, Triplet count level, indicated by the grayscale at bottom, as a function of lag (t_b - t_a) between cells labeled b and a (horizontal) and lag (t_c- t_a) between cells labeled c and a (vertical). Bin widths are 0.9 × 0.9 msec. Pairwise correlations are shown along the outside, in bin widths of 0.9 msec. For (ab) pair correlation, count indicators are 400 and 600; for (bc) and (ac), count indicators are 600 and 800. Data acquired over 5 min of recording; over this span, cell a fired 8727 spikes (highest threshold), cell b fired 11,676 spikes (no threshold), and cell c fired 15,215 spikes (no threshold).

Figure 7.

Interspike intervals become more regular at higher rate. Coefficient of variation for two cells of a pair plotted against firing rate of each cell. Labels for the left panel also apply to the right panel.