Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans

Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented—animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner. We show that the Caenorhabditis elegans orthologues of Ca 2+ /calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs. In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type). Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.

Pupillary Correlates of Fluctuations in Sustained Attention

The current study examined pupillary correlates of fluctuations and lapses of sustained attention. Participants performed a sustained attention task with either a varied ISI or a fixed ISI (fixed at 2 or 8 sec) while pupil responses were continuously recorded. The results indicated that performance was worse when the ISI was varied or fixed at 8 sec compared with when the ISI was fixed at 2 sec, suggesting that varied or long ISI conditions require greater intrinsic alertness compared with constant short ISIs. In terms of pupillary responses, the results demonstrated that slow responses (indicative of lapses) were associated with greater variability in tonic pupil diameter, smaller dilation responses during the ISI, and subsequently smaller dilation responses to stimulus onset. These results suggest that lapses of attention are associated with lower intrinsic alertness, resulting in a lowered intensity of attention to task-relevant stimuli. Following a lapse of attention, performance, tonic pupil diameter, and phasic pupillary responses, all increased, suggesting that attention was reoriented to the task. These results are consistent with the notion that pupillary responses track fluctuations in sustained attention.

Short interspike intervals and double discharges of anconeus motor unit action potentials for the production of dynamic elbow extensions

Incidence of double discharges (DDs; >100 Hz) and short interspike intervals (ISIs; >50 to <100 Hz) is reported to vary widely among different muscles and tasks, with a higher incidence in motor unit (MU) trains of fast muscles and for the production of fast contractions in humans. However, it is unclear whether human muscles with a large composition of slower motor units exhibit DDs or short ISIs when activated with maximal synaptic drive, such as those required for maximal velocity dynamic contractions. Thus the purpose of this study was to determine the effect of increasing peak contraction velocity on the incidence of DDs and short ISIs in the anconeus muscle. Seventeen anconeus MUs in 10 young males were recorded across dynamic elbow extensions ranging from low submaximal velocities (16% of maximal velocity) up to maximal velocities. A low incidence of DDs (4%) and short ISIs (29%) was observed among the 583 MU trains recorded. Despite the low incidence in individual MU trains, a majority (71% and 94%, respectively) of MUs exhibited at least one DD or short ISI. The number of short ISIs shared no variance with MU recruitment threshold ( R2 = 0.02), but their distribution was skewed toward higher peak velocities ( G = −1.26) and a main effect of peak elbow extension velocity was observed ( P < 0.05). Although a greater number of short ISIs was observed with increasing velocity, the low incidence of DDs and short ISIs in the anconeus muscle is likely related to the function of the anconeus as a stabilizer rather than voluntary elbow extensor torque and velocity production.

Auditory Temporal Order Discrimination and Backward Recognition Masking in Adults With Dyslexia

The ability of 20 adult dyslexic readers to extract frequency information from successive tone pairs was compared with that of IQ-matched controls using temporal order discrimination and auditory backward recognition masking (ABRM) tasks. In both paradigms, the interstimulus interval (ISI) between tones in a pair was either short (20 ms) or long (200 ms). Temporal order discrimination was better for both groups of listeners at long than at short ISIs, but no group differences in performance were observed at either ISI. Performance on the ABRM task was also better at long than at short ISIs and was influenced by variability in masker frequency and by the spectral proximity of target and masker. The only significant group difference was found in one condition of the ABRM task when the target-masker interval was 200 ms, but this difference was not reliable when the measure was of optimal performance. Moderate correlations were observed between auditory thresholds and phonological skill for the sample as a whole and within the dyslexic and control groups. However, although a small subgroup of dyslexic listeners with poor phonology was characterized by elevated thresholds across the auditory tasks, evidence for an association between auditory and phonological processing skills was weakened by the finding of a subgroup of control listeners with poor auditory processing and normal phonological processing skills.

Discharge patterns in human motor units during fatiguing arm movements

The purpose of this study was to determine whether short interspike intervals (ISIs of <20 ms) would occur naturally during voluntary movement and would increase in number with fatigue. Thirty-four triceps brachii motor units from nine subjects were assessed during a fatigue task consisting of fifty extension and fifty flexion elbow movements against a constant-load opposing extension. Nineteen motor units were recorded from the beginning of the fatigue task; the number of short ISIs was 7.1 ± 4.1% of the total number of ISIs in the first one-third of the task (unfatigued state). This value increased to 11.8 ± 5.9% for the last one-third of the task (fatigued state). Fifteen motor units were recruited during the fatigue task and discharged, with 16.4 ± 6.0% of short ISIs in the fatigued state. For all motor units, the number of short ISIs was positively correlated ( r 2 = 0.85) with the recruitment threshold torque. Short ISIs occurred most frequently at movement initiation but also occurred throughout the movement. These results document the presence of short ISIs during voluntary movement and their increase in number during fatigue.

Effects of Prime Type and Delay on Multiplication Priming: Evidence for a Dual-process Model

Two experiments investigated effects of numerical primes on production of simple multiplication facts (e.g. 4 × 8 = ?). In Experiment 1, a correct (32), related (24), unrelated (27), or neutral (##) prime appeared for 200 msec and was followed by a target problem at an ISI of 0, 750, or 1500 msec. Relative to neutral primes, correct primes produced constant RT and accuracy benefits across ISIs, and unrelated primes produced constant RT costs. Related primes produced costs compared to unrelated primes at the 0-msec ISI only. In Experiment 2, eliminating correct-answer primes from the stimulus set eliminated all the false-prime effects except the costs of related primes at the 0-msec ISI. We propose a dual-process account incorporating a familiarity-based name-the-prime strategy that produces benefits and costs insensitive to ISI and an automatic retrieval-priming process that is measurable only at short ISIs.

The Discrimination of Dynamic Orientation Changes in Gratings

Thresholds were measured for discrimination of direction of a step angular rotation of gratings. The addition of simultaneous phase displacements (translation) had little effect on rotation thresholds for gratings over a considerable range; discrimination of rotation is unaffected by random directional translations an order of magnitude larger. Angular rotation discrimination thresholds increased with interstimulus interval (ISI). Thus discrimination is based at short ISIs (180 ms or less) on a percept of rotary motion, but at ISIs of several seconds by a spatial strategy (comparing static component orientations) relying on visual memory. Data points for the short-ISI region fell below the best-fitting straight line, and the slope of the short-ISI region of the curve was steeper than that of the long-ISI region. However, when either compound or simple gratings with uncorrelated spatial frequencies were used in the two stimulus frames, there was no evidence for a separate function at short ISIs. Orientation-change thresholds were measured for simple gratings as a function of contrast and spatial frequency. The contrast function showed saturation and the spatial frequency function was U-shaped. Rotation sensitivity for gratings is thus similar in its spatiotemporal properties to translation sensitivity. The findings support the proposal that rotation discrimination (at short ISIs) is achieved by a template mechanism combining signals from different directional detectors, rather than by cognitive comparison of the outputs of the directional mechanisms themselves.