Spinal Basis of Direction Control during Locomotion in Larval Zebrafish.

Navigation requires steering and propulsion, but how spinal circuits contribute to direction control during ongoing locomotion is not well understood. Here, we use drifting vertical gratings to evoke directed "fictive" swimming in intact but immobilized larval zebrafish while performing electrophysiological recordings from spinal neurons. We find that directed swimming involves unilateral changes in the duration of motor output and increased recruitment of motor neurons, without impacting the timing of spiking across or along the body. Voltage-clamp recordings from motor neurons reveal increases in phasic excitation and inhibition on the side of the turn. Current-clamp recordings from premotor interneurons that provide phasic excitation or inhibition reveal two types of recruitment patterns. A direction-agnostic pattern with balanced recruitment on the turning and nonturning sides is primarily observed in excitatory V2a neurons with ipsilateral descending axons, while a direction-sensitive pattern with preferential recruitment on the turning side is dominated by V2a neurons with ipsilateral bifurcating axons. Inhibitory V1 neurons are also divided into direction-sensitive and direction-agnostic subsets, although there is no detectable morphologic distinction. Our findings support the modular control of steering and propulsion by spinal premotor circuits, where recruitment of distinct subsets of excitatory and inhibitory interneurons provide adjustments in direction while on the move.SIGNIFICANCE STATEMENT Spinal circuits play an essential role in coordinating movements during locomotion. However, it is unclear how they participate in adjustments in direction that do not interfere with coordination. Here we have developed a system using larval zebrafish that allows us to directly record electrical signals from spinal neurons during "fictive" swimming guided by visual cues. We find there are subsets of spinal interneurons for coordination and others that drive unilateral asymmetries in motor neuron recruitment for direction control. Our findings suggest a modular organization of spinal premotor circuits that enables uninterrupted adjustments in direction during ongoing locomotion.

Reading text aloud benefits memory but not comprehension.

The production effect-that reading aloud leads to better memory than does reading silently-has been defined narrowly with reference to memory; it has been explored largely using word lists as the material to be read and remembered. But might the benefit of production extend beyond memory and beyond individual words? In a series of four experiments, passages from reading comprehension tests served as the study material. Participants read some passages aloud and others silently. After each passage, they completed multiple-choice questions about that passage. Separating the multiple-choice questions into memory-focused versus comprehension-focused questions, we observed a consistent production benefit only for the memory-focused questions. Production clearly improves memory for text, not just for individual words, and also extends to multiple-choice testing. The overall pattern of findings fits with the distinctiveness account of production-that information read aloud stands out at study and at test from information read silently. Only when the tested information is a very close match to the studied information, as is the case for memory questions but not for comprehension questions, does production improve accuracy.

Chemoselective Oxidation of Alcohols in the Presence of Amines Using an Oxoammonium Salt.

The oxidation of alcohols in the presence of reactive amines employing the commercially available oxoammonium cation, "Bobbitt's salt" is described. The oxidation is accomplished under acidic conditions and subsequent treatment with a suitable base affords a convenient one-pot method to access imines in good to excellent isolated yields (74-99%).

Sports and trauma as risk factors for Motor Neurone Disease: New Zealand case-control study.

OBJECTIVES: To assess whether sports, physical trauma and emotional trauma are associated with motor neurone disease (MND) in a New Zealand case-control study (2013-2016). METHODS: In total, 321 MND cases and 605 population controls were interviewed collecting information on lifetime histories of playing sports, physical trauma (head injury with concussion, spine injury) and emotional trauma (14 categories). ORs were estimated using logistic regression adjusting for age, sex, ethnicity, socioeconomic status, education, smoking status, alcohol consumption and mutually adjusting for all other exposures. RESULTS: Head injury with concussion ≥3 years before diagnosis was associated with MND (OR 1.51, 95% CI: 1.09-2.09), with strongest associations for two (OR 4.01, 95% CI: 1.82-8.86), and three or more (OR 2.34, 95% CI: 1.00-5.45) head injuries. Spine injury was not associated with MND (OR 0.81, 95% CI: 0.48-1.36). Compared to never playing sports, engaging in sports throughout childhood and adulthood increased MND risk (OR 1.81, 95% CI: 1.01-3.25), as was more than 12 years playing football/soccer (OR 2.35, 95% CI: 1.19-4.65). Reporting emotionally traumatic events in more than three categories was associated with MND (OR 1.88, 95% CI: 1.17-3.03), with physical childhood abuse the only specific emotional trauma associated with MND (OR 1.82, 95% CI: 1.14-2.90), particularly for those reporting longer abuse duration (OR(5-8 years) 2.26, 95% CI: 1.14-4.49; OR(>8 years) 3.01, 95% CI: 1.18-7.70). For females, having witnessed another person being killed, seriously injured or assaulted also increased MND risk (OR 2.68, 95% CI: 1.06-6.76). CONCLUSIONS: This study adds to the evidence that repeated head injury with concussion, playing sports in general, and playing football (soccer) in particular, are associated with an increased risk of MND. Emotional trauma, that is physical abuse in childhood, may also play a role.

Occupational exposures to pesticides and other chemicals: a New Zealand motor neuron disease case-control study.

OBJECTIVES: To assess associations between occupational exposures to pesticides and other chemicals and motor neuron disease (MND). METHODS: A population-based case-control study that included 319 MND cases (64% male/36% female) recruited through the New Zealand MND Association complemented with hospital discharge data, and 604 controls identified from the Electoral Roll. For each job held, a questionnaire collected information on 11 exposure categories (dust, fibres, tobacco smoke, fumes, gas, fumigants, oils/solvents, acids/alkalis, pesticides, other chemicals and animals/animal products). ORs were estimated using logistic regression adjusting for age, sex, ethnicity, socioeconomic status, education, smoking, alcohol consumption, physical activities, head/spine injury and other occupational exposures. RESULTS: Two exposure categories were associated with increased MND risks: pesticides (OR 1.70, 95% CI 1.17 to 2.48) and fumigants (OR 3.98, 95% CI 1.81 to 8.76), with risks increasing with longer exposure duration (p<0.01). Associations were also observed for: methyl bromide (OR 5.28, 95% CI 1.63 to 17.15), organochlorine insecticides (OR 3.28, 95% CI 1.18 to 9.07), organophosphate insecticides (OR 3.11, 95% CI 1.40 to 6.94), pyrethroid insecticides (OR 6.38, 95% CI 1.13 to 35.96), inorganic (copper) fungicides (OR 4.66, 95% CI 1.53 to 14.19), petrol/diesel fuel (OR 2.24, 95% CI 1.27 to 3.93) and unspecified solvents (OR 1.91, 95% CI 1.22 to 2.99). In women, exposure to textile fibres (OR 2.49, 95% CI 1.13 to 5.50), disinfectants (OR 9.66, 95% CI 1.29 to 72.44) and cleaning products (OR 3.53, 95% CI 1.64 to 7.59) were also associated with MND; this was not observed in men (OR 0.80, 95% CI 0.44 to 1.48; OR 0.72, 95% CI 0.29 to 1.84; OR 0.57, 95% CI 0.21 to 1.56, respectively). CONCLUSIONS: This study adds to the evidence that pesticides, especially insecticides, fungicides, and fumigants, are risk factors for MND.

Integration of Swimming-Related Synaptic Excitation and Inhibition by olig2+ Eurydendroid Neurons in Larval Zebrafish Cerebellum.

The cerebellum influences motor control through Purkinje target neurons, which transmit cerebellar output. Such output is required, for instance, for larval zebrafish to learn conditioned fictive swimming. The output cells, called eurydendroid neurons (ENs) in teleost fish, are inhibited by Purkinje cells and excited by parallel fibers. Here, we investigated the electrophysiological properties of glutamatergic ENs labeled by the transcription factor olig2. Action potential firing and synaptic responses were recorded in current clamp and voltage clamp from olig2+ neurons in immobilized larval zebrafish (before sexual differentiation) and were correlated with motor behavior by simultaneous recording of fictive swimming. In the absence of swimming, olig2+ ENs had basal firing rates near 8 spikes/s, and EPSCs and IPSCs were evident. Comparing Purkinje firing rates and eurydendroid IPSC rates indicated that 1-3 Purkinje cells converge onto each EN. Optogenetically suppressing Purkinje simple spikes, while preserving complex spikes, suggested that eurydendroid IPSC size depended on presynaptic spike duration rather than amplitude. During swimming, EPSC and IPSC rates increased. Total excitatory and inhibitory currents during sensory-evoked swimming were both more than double those during spontaneous swimming. During both spontaneous and sensory-evoked swimming, the total inhibitory current was more than threefold larger than the excitatory current. Firing rates of ENs nevertheless increased, suggesting that the relative timing of IPSCs and EPSCs may permit excitation to drive additional eurydendroid spikes. The data indicate that olig2+ cells are ENs whose activity is modulated with locomotion, suiting them to participate in sensorimotor integration associated with cerebellum-dependent learning.SIGNIFICANCE STATEMENT The cerebellum contributes to movements through signals generated by cerebellar output neurons, called eurydendroid neurons (ENs) in fish (cerebellar nuclei in mammals). ENs receive sensory and motor signals from excitatory parallel fibers and inhibitory Purkinje cells. Here, we report electrophysiological recordings from ENs of larval zebrafish that directly illustrate how synaptic inhibition and excitation are integrated by cerebellar output neurons in association with motor behavior. The results demonstrate that inhibitory and excitatory drive both increase during fictive swimming, but inhibition greatly exceeds excitation. Firing rates nevertheless increase, providing evidence that synaptic integration promotes cerebellar output during locomotion. The data offer a basis for comparing aspects of cerebellar coding that are conserved and that diverge across vertebrates.

Intersection of motor volumes predicts the outcome of ambush predation of larval zebrafish.

Escape maneuvers are key determinants of animal survival and are under intense selection pressure. A number of escape maneuver parameters contribute to survival, including response latency, escape speed and direction. However, the relative importance of these parameters is context dependent, suggesting that interactions between parameters and predatory context determine the likelihood of escape success. To better understand how escape maneuver parameters interact and contribute to survival, we analyzed the responses of larval zebrafish (Danio rerio) to the attacks of dragonfly nymphs (Sympetrum vicinum). We found that no single parameter explains the outcome. Instead, the relative intersection of the swept volume of the nymph's grasping organs with the volume containing all possible escape trajectories of the fish is the strongest predictor of escape success. In cases where the prey's motor volume exceeds that of the predator, the prey survives. By analyzing the intersection of these volumes, we compute the survival benefit of recruiting the Mauthner cell, a neuron in anamniotes devoted to producing escapes. We discuss how the intersection of motor volume approach provides a framework that unifies the influence of many escape maneuver parameters on the likelihood of survival.

Intention and performance when reading aloud: Context is everything.

A widely held account asserts that single words are automatically identified in the absence of an intent to process them in the form of identifying a task set, and implementing it. We provide novel evidence that there is no fixed relation between intention and visual word identification. Subjects were randomly cued on a trial-by-trial basis as to whether to read aloud a single target word (Go) or not (No-go). When the Go-No Go probability was 50% (Experiment 1) the effect of stimulus quality (bright vs. dim targets) was the same size as in a separate block of 100% Go trials. In Experiment 2, where the Go-No Go probability was 80% in the cued condition, the stimulus quality effect was smaller than in the block of all Go trials. These results can be understood in terms of Go trial probability moderating whether subjects (i) hold off beginning to process the target until an intention in the form of a Task Set has been implemented, or (ii) begin to identify the target during the time taken to implement a Task Set. The additivity of stimulus quality and cueing conditions in Experiment 1 support the view that target processing only begins when a Task Set is in place, whereas the under-additivity of stimulus quality and cueing condition in Experiment 2 supports the interpretation that target identification can start during the time that a Task Set is being implemented. Taken together with other results, we conclude that there is no fixed relation between an intention and word identification; context is everything.

Society for Maternal-Fetal Medicine Special Statement: A maternal transport briefing form and checklist.

When performing a maternal transport between two facilities, numerous pieces of information must be communicated between physicians, nurses, and transport personnel, including the health status of 2 patients (mother and fetus), availability of bed space and personnel in 2 units at the receiving facility (labor and delivery unit and neonatal intensive care unit), arrangements for transportation, and inpatient and outpatient records. The amount and complexity of information creates a risk of medical error due to communication lapses. A cognitive aid such as a standardized form can help the team prepare for a transfer and provide a consistent framework for a handoff briefing among healthcare professionals. SMFM presents a sample briefing form to ensure that key elements are communicated for every maternal transport. Practical suggestions are given to help facilities customize the form and implement it on their units.

Occupation and motor neuron disease: a New Zealand case-control study.

OBJECTIVES: To assess associations between occupation and motor neuron disease (MND). METHODS: We conducted a population-based case-control study with cases (n=321) recruited through the New Zealand Motor Neurone Disease Association and hospital discharge data. Controls (n=605) were recruited from the Electoral Roll. Information on personal and demographic details, lifestyle factors and a full occupational history was collected using questionnaires and interviews. Associations with ever/never employed and employment duration were estimated using logistic regression stratified by sex and adjusted for age, ethnicity, socioeconomic deprivation, education and smoking. RESULTS: Elevated risks were observed for field crop and vegetable growers (OR 2.93, 95% CI 1.10 to 7.77); fruit growers (OR 2.03, 95% CI 1.09 to 3.78); gardeners and nursery growers (OR 1.96, 95% CI 1.01 to 3.82); crop and livestock producers (OR 3.61, 95% CI 1.44 to 9.02); fishery workers, hunters and trappers (OR 5.62, 95% CI 1.27 to 24.97); builders (OR 2.90, 95% CI 1.41 to 5.96); electricians (OR 3.61, 95% CI 1.34 to 9.74); caregivers (OR 2.65, 95% CI 1.04 to 6.79); forecourt attendants (OR 8.31, 95% CI 1.79 to 38.54); plant and machine operators and assemblers (OR 1.42, 95% CI 1.01 to 2.01); telecommunications technicians (OR 4.2, 95% CI 1.20 to 14.64); and draughting technicians (OR 3.02, 95% CI 1.07 to 8.53). Industries with increased risks were agriculture (particularly horticulture and fruit growing), construction, non-residential care services, motor vehicle retailing, and sport and recreation. Positive associations between employment duration and MND were shown for the occupations fruit growers, gardeners and nursery growers, and crop and livestock producers, and for the horticulture and fruit growing industry. CONCLUSIONS: This study suggests associations between MND and occupations in agriculture and several other occupations.

Integrated one- and two-photon scanned oblique plane illumination (SOPi) microscopy for rapid volumetric imaging.

Versatile, sterically accessible imaging systems capable of in vivo rapid volumetric functional and structural imaging deep in the brain continue to be a limiting factor in neuroscience research. Towards overcoming this obstacle, we present integrated one- and two-photon scanned oblique plane illumination (SOPi, /sopi/) microscopy which uses a single front-facing microscope objective to provide light-sheet scanning based rapid volumetric imaging capability at subcellular resolution. Our planar scan-mirror based optimized light-sheet architecture allows for non-distorted scanning of volume samples, simplifying accurate reconstruction of the imaged volume. Integration of both one-photon (1P) and two-photon (2P) light-sheet microscopy in the same system allows for easy selection between rapid volumetric imaging and higher resolution imaging in scattering media. Using SOPi, we demonstrate deep, large volume imaging capability inside scattering mouse brain sections and rapid imaging speeds up to 10 volumes per second in zebrafish larvae expressing genetically encoded fluorescent proteins GFP or GCaMP6s. SOPi's flexibility and steric access makes it adaptable for numerous imaging applications and broadly compatible with orthogonal techniques for actuating or interrogating neuronal structure and activity.

Occupational solvent exposure and risk of glioma in the INTEROCC study.

BACKGROUND: The aetiology of glioma remains largely unknown. Occupational solvent exposure has been suggested as a putative cause of glioma, but past studies have been inconsistent. We examined the association between a range of solvents and glioma risk within the INTEROCC project, a study of brain tumours and occupational exposures based on data from seven national case-control studies conducted in the framework of the INTERPHONE study. We also investigated associations according to tumour grade. METHODS: Data from the seven countries were standardised and then combined into one aggregate data set. Pooled odds ratios (ORs) were estimated for adjusted models that included sex, age, country-region of residence and level of educational attainment. Exposures to any solvent or 11 specific solvents or subgroups were assessed using a modified version of the FINJEM job exposure matrix (JEM) specifically developed for the study, called INTEROCC-JEM. RESULTS: Analysis included 2000 glioma cases and 5565 controls. For glioma and ever/never exposure to any solvent, the OR was 0.91 (95% confidence interval: 0.74-1.11). All ORs were <1.0 for specific solvents/subgroups. There were no increases in risk according to high or low grade of tumour. CONCLUSIONS: The results of this study show no consistent associations for any solvent exposures overall or by grade of tumour.

Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case-control study.

BACKGROUND: Brain tumor etiology is poorly understood. Based on their ability to pass through the blood-brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent. METHODS: We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30-69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM. RESULTS: In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7-1.0) for lead to 1.1 (0.7-1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted. CONCLUSIONS: Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma.

Systematic shifts in the balance of excitation and inhibition coordinate the activity of axial motor pools at different speeds of locomotion.

An emerging consensus from studies of axial and limb networks is that different premotor populations are required for different speeds of locomotion. An important but unresolved issue is why this occurs. Here, we perform voltage-clamp recordings from axial motoneurons in larval zebrafish during "fictive" swimming to test the idea that systematic differences in the biophysical properties of axial motoneurons are associated with differential tuning in the weight and timing of synaptic drive, which would help explain premotor population shifts. We find that increases in swimming speed are accompanied by increases in excitation preferentially to lower input resistance (Rin) motoneurons, whereas inhibition uniformly increases with speed to all motoneurons regardless of Rin. Additionally, while the timing of rhythmic excitatory drive sharpens within the pool as speed increases, there are shifts in the dominant source of inhibition related to Rin. At slow speeds, anti-phase inhibition is larger throughout the pool. However, as swimming speeds up, inhibition arriving in-phase with local motor activity increases, particularly in higher Rin motoneurons. Thus, in addition to systematic differences in the weight and timing of excitation related to Rin and speed, there are also speed-dependent shifts in the balance of different sources of inhibition, which is most obvious in more excitable motor pools. We conclude that synaptic drive is differentially tuned to the biophysical properties of motoneurons and argue that differences in premotor circuits exist to simplify the coordination of activity within spinal motor pools during changes in locomotor speed.

Answers at your fingertips: Access to the Internet influences willingness to answer questions.

Recent technological advances have given rise to an information-gathering tool unparalleled by any in human history-the Internet. Understanding how access to such a powerful informational tool influences how we think represents an important question for psychological science. In the present investigation we examined the impact of access to the Internet on the metacognitive processes that govern our decisions about what we "know" and "don't know." Results demonstrated that access to the Internet influenced individuals' willingness to volunteer answers, which led to fewer correct answers overall but greater accuracy when an answer was offered. Critically, access to the Internet also influenced feeling-of-knowing, and this accounted for some (but not all) of the effect on willingness to volunteer answers. These findings demonstrate that access to the Internet can influence metacognitive processes, and contribute novel insights into the operation of the transactive memory system formed by people and the Internet.

Real-time visualization of melanin granules in normal human skin using combined multiphoton and reflectance confocal microscopy.

BACKGROUND: Recent advances in biomedical optics have enabled dermal and epidermal components to be visualized at subcellular resolution and assessed noninvasively. Multiphoton microscopy (MPM) and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that have demonstrated promising results in imaging skin micromorphology, and which provide complementary information regarding skin components. This study assesses whether combined MPM/RCM can visualize intracellular and extracellular melanin granules in the epidermis and dermis of normal human skin. METHODS: We perform MPM and RCM imaging of in vivo and ex vivo skin in the infrared domain. The inherent three-dimensional optical sectioning capability of MPM/RCM is used to image high-contrast granular features across skin depths ranging from 50 to 90 µm. The optical images thus obtained were correlated with conventional histologic examination including melanin-specific staining of ex vivo specimens. RESULTS: MPM revealed highly fluorescent granular structures below the dermal-epidermal junction (DEJ) region. Histochemical staining also demonstrated melanin-containing granules that correlate well in size and location with the granular fluorescent structures observed in MPM. Furthermore, the MPM fluorescence excitation wavelength and RCM reflectance of cell culture-derived melanin were equivalent to those of the granules. CONCLUSION: This study suggests that MPM can noninvasively visualize and quantify subepidermal melanin in situ.

Distinct familiarity-based response patterns for faces and buildings in perirhinal and parahippocampal cortex.

An unresolved question in our understanding of the medial temporal lobes is how functional differences between structures pertaining to stimulus category relate to the distinction between item-based and contextually based recognition-memory processes. Specifically, it remains unclear whether perirhinal cortex (PrC) supports item-based familiarity signals for all stimulus categories or whether parahippocampal cortex (PhC) may also play a role for stimulus categories that are known to engage this structure in other task contexts. Here, we used multivoxel pattern analyses of fMRI data to compare patterns of activity in humans that are associated with the perceived familiarity of faces, buildings, and chairs. During scanning, participants judged the familiarity of previously studied and novel items from all three categories. Instances in which recognition was based on recollection were removed from all analyses. In right PrC, we found patterns of activity that distinguished familiar from novel faces. By contrast, in right PhC, we observed such patterns for buildings. Familiarity signals for chairs were present in both structures but shared little overlap with the patterns observed for faces and buildings on a more fine-grained scale. In the hippocampus, we found no evidence for familiarity signals for any object category. Our findings show that both PrC and PhC contribute to the assessment of item familiarity. They suggest that PhC does not only represent episodic context but can also represent item information for some object categories in recognition-memory decisions. In turn, our findings also indicate that the involvement of PrC in representing item familiarity is not ubiquitous.

Label-free identification and characterization of murine hair follicle stem cells located in thin tissue sections with Raman micro-spectroscopy.

Stem cells offer tremendous opportunities for regenerative medicine. Over the past decade considerable research has taken place to identify and characterize the differentiation states of stem cells in culture. Raman micro-spectroscopy has emerged as an ideal technology since it is fast, nondestructive, and does not require potentially toxic dyes. Raman spectroscopy systems can also be incorporated into confocal microscope imaging systems allowing spectra to be obtained from below the tissue surface. Thus there is significant potential for monitoring stem cells in living tissue. Stem cells that reside in hair follicles are suitable for testing this possibility since they are close to the skin surface, and typically clustered around the bulge area. One of the first steps needed would be to obtain Raman micro-spectra from stem cells located in thin sections of tissue, and then see whether these spectra are clearly different from those of the surrounding differentiated cells. To facilitate this test, standard 5 µm thick sections of murine skin tissue were stained to identify the location of hair follicle stem cells and their progeny. Raman spectra were then obtained from adjacent cells in a subsequent unstained 10 µm thick section. The spectra revealed significant differences in peak intensities associated with nucleic acids, proteins, lipids and amino acids. Statistical analyses of the Raman micro-spectra identified stem cells with 98% sensitivity and 94% specificity, as compared with a CD34 immunostaining gold standard. Furthermore analyses of the spectral variance indicated differences in cellular dynamics between the two cell groups. This study shows that Raman micro-spectroscopy has a potential role in identifying adult follicle stem cells, laying the groundwork for future applications of hair follicle stem cells and other somatic stem cells in situ.

Cell-type-specific origins of locomotor rhythmicity at different speeds in larval zebrafish.

Different speeds of locomotion require heterogeneous spinal populations, but a common mode of rhythm generation is presumed to exist. Here, we explore the cellular versus synaptic origins of spinal rhythmicity at different speeds by performing electrophysiological recordings from premotor excitatory interneurons in larval zebrafish. Chx10-labeled V2a neurons are divided into at least two morphological subtypes proposed to play distinct roles in timing and intensity control. Consistent with distinct rhythm generating and output patterning functions within the spinal V2a population, we find that descending subtypes are recruited exclusively at slow or fast speeds and exhibit intrinsic cellular properties suitable for rhythmogenesis at those speeds, while bifurcating subtypes are recruited more reliably at all speeds and lack appropriate rhythmogenic cellular properties. Unexpectedly, however, phasic firing patterns during locomotion in rhythmogenic and non-rhythmogenic V2a neurons alike are best explained by distinct modes of synaptic inhibition linked to cell-type and speed. At fast speeds reciprocal inhibition in descending V2a neurons supports phasic firing, while recurrent inhibition in bifurcating V2a neurons helps pattern motor output. In contrast, at slow speeds recurrent inhibition in descending V2a neurons supports phasic firing, while bifurcating V2a neurons rely on reciprocal inhibition alone to pattern output. Our findings suggest cell-type-specific, not common, modes of rhythmogenesis generate and coordinate different speeds of locomotion.

Release from response interference in color-word contingency learning.

In identifying the print colors of words when some combinations of color and word occur more frequently than others, people quickly show evidence of learning these associations. This contingency learning effect is evident in faster and more accurate responses to high-contingency combinations than to low-contingency combinations. Across four experiments, we systematically varied the number of response-irrelevant word stimuli connected to response-relevant colors. In each experiment, one group experienced the typical contingency learning paradigm with three colors linked to three words; other groups saw more words (six or twelve) linked to the same three colors. All four experiments disconfirmed a central prediction derived from the Parallel Episodic Processing (PEP 2.0) model (Schmidt et al., 2016)-that the magnitude of the contingency learning effect should remain stable as more words are added to the response-irrelevant dimension, as long as the color-word contingency ratios are maintained. Responses to high-contingency items did slow down numerically as the number of words increased between groups, consistent with the prediction from PEP 2.0, but these changes were unreliable. Inconsistent with PEP 2.0, however, overall response time did not slow down and responses to low-contingency items actually sped up as the number of words increased across groups. These findings suggest that the PEP 2.0 model should be modified to incorporate response interference caused by high-probability associations when responding to low-probability combinations.