Dégénérescence rétinienne chez la souris rd10 Implication de SIRT 1 et PGC-1 alpha ?

PARIS5-BU Méd.Cochin (751142101) / SudocSudocFranceF

A subanesthetic dose of ketamine in the Rhesus monkey reduces the occurrence of anticipatory saccades

RATIONALE: It has been shown that antagonism of the glutamatergic N-methyl-D-aspartate (NMDA) receptor with subanesthetic doses of ketamine perturbs the perception of elapsed time. Anticipatory eye movements are based on an internal representation of elapsed time. Therefore, the occurrence of anticipatory saccades could be a particularly sensitive indicator of abnormal time perception due to NMDA receptors blockade. OBJECTIVES: To determine whether the occurrence of anticipatory saccades could be selectively altered by a subanesthetic dose of ketamine. METHODS: Three Rhesus monkeys were trained in a simple visually-guided saccadic task with a variable delay. Monkeys were rewarded for making a visually-guided saccade at the end of the delay. Premature anticipatory saccades to the future position of the eccentric target initiated before the end of the delay were not rewarded. A sub-anesthetic dose of ketamine (0.25 mg/kg) or a saline solution of the same volume was injected i.m. during the task. RESULTS: We found that the injected dose of ketamine did not induce sedation or abnormal behavior. However, in ~4 minutes, ketamine induced a strong reduction of the occurrence of anticipatory saccades but did not reduce the occurrence of visually-guided saccades. CONCLUSION: This unexpected reduction of anticipatory saccade occurrence could be interpreted as resulting from an altered use of the perception of elapsed time during the delay period induced by NMDA receptors antagonism

Implicit and explicit timing in oculomotor control.

The passage of time can be estimated either explicitly, e.g. before leaving home in the morning, or implicitly, e.g. when catching a flying ball. In the present study, the latency of saccadic eye movements was used to evaluate differences between implicit and explicit timing. Humans were required to make a saccade between a central and a peripheral position on a computer screen. The delay between the extinction of a central target and the appearance of an eccentric target was the independent variable that could take one out of four different values (400, 900, 1400 or 1900 ms). In target trials, the delay period lasted for one of the four durations randomly. At the end of the delay, a saccade was initiated by the appearance of an eccentric target. Cue&target trials were similar to target trials but the duration of the delay was visually cued. In probe trials, the duration of the upcoming delay was cued, but there was no eccentric target and subjects had to internally generate a saccade at the estimated end of the delay. In target and cue&target trials, the mean and variance of latency distributions decreased as delay duration increased. In cue&target trials latencies were shorter. In probe trials, the variance increased with increasing delay duration and scalar variability was observed. The major differences in saccadic latency distributions were observed between visually-guided (target and cue&target trials) and internally-generated saccades (probe trials). In target and cue&target trials the timing of the response was implicit. In probe trials, the timing of the response was internally-generated and explicitly based on the duration of the visual cue. Scalar timing was observed only during probe trials. This study supports the hypothesis that there is no ubiquitous timing system in the brain but independent timing processes active depending on task demands

Histograms of saccadic absolute latencies in <i>target</i> trials.

<p>Time zero on the abscissa represents the beginning of the delay period. The time elapsed until the appearance of the eccentric target is represented with <i>vertical dashed lines</i> for the four different durations tested. The ordinate represents the number of saccades in the 10-ms bins.</p

Histograms of saccadic absolute latencies in the <i>probe</i> trials.

<p>X-axis: saccadic absolute latencies; Y-axis: number of saccades in the 100-ms bins. Note the increasing spread of the latencies with increasing delay duration. Vertical dashed lines: time of target appearance in cue&target trials.</p

Histograms of absolute saccadic latencies in <i>cue&target</i> trials.

<p>The ordinate represents the percentage of saccades in the 100-ms bins for each of the 4 delay durations independently. The abscissa represents the time elapsed until the appearance of the eccentric target (<i>vertical dashed lines</i>).</p

Summary of descriptive statistics.

<p>Group data of all subjects. <i>N</i>, sample size; <i>STD</i>, standard deviation, <i>CV</i>, coefficient of variation (STD/mean absolute latency); <i>(r)</i>, randomized durations blocks of trials, variable foreperiod; <i>(b)</i>, single duration blocks of trials, fixed foreperiod. <b>Bold type</b> is used to indicate trials collected in blocks with P(<i>probe</i>) = 0.5.</p

Comparison of variable and fixed foreperiods.

<p>Mean latency (±2 SE) as a function of delay duration in <i>target</i> trials. Variable foreperiod (<i>Variable</i>) and fixed foreperiod blocks of trials (<i>Fixed</i>). In the variable foreperiod condition, mean latencies were longer for 400 ms delay duration. An opposite trend was found in the fixed foreperiod condition. Group data from 6 subjects (6/9) who participated in this control experiment.</p

Group data in <i>probe</i> trials.

<p><i>A</i>: mean absolute latency (±2 SE) as a function of delay duration. <i>B</i>: Latency variance for the same data. <i>C</i>: Mean relative latency (±2 SE). The horizontal dashed line represents the transition between saccades occurring after the end of the cued duration (positive values) or before (negative values).</p

Comparison of <i>target</i> and <i>cue&target</i> trials.

<p>A: Mean relative latency (±2 SE) as a function of delay duration in <i>cue&target</i> (dashed line) and, for comparison, <i>target</i> trials (continuous line). B: Latency variance in <i>cue&target</i> and <i>target</i> trials.</p