A longitudinal study of epigenetic variation in twins.

DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. Alterations in DNA methylation are established contributors to inter-individual phenotypic variation and have been associated with disease susceptibility. The degree to which changes in loci-specific DNA methylation are under the influence of heritable and environmental factors is largely unknown. In this study, we quantitatively measured DNA methylation across the promoter regions of the dopamine receptor 4 gene (DRD4), the serotonin transporter gene (SLC6A4/SERT) and the X-linked monoamine oxidase A gene (MAOA) using DNA sampled at both ages 5 and 10 years in 46 MZ twin-pairs and 45 DZ twin-pairs (total n=182). Our data suggest that DNA methylation differences are apparent already in early childhood, even between genetically identical individuals, and that individual differences in methylation are not stable over time. Our longitudinal-developmental study suggests that environmental influences are important factors accounting for interindividual DNA methylation differences, and that these influences differ across the genome. The observation of dynamic changes in DNA methylation over time highlights the importance of longitudinal research designs for epigenetic research.

Exploring the role of the substantia nigra pars reticulata in eye movements.

Experiments that demonstrated a role for the substantia nigra in eye movements have played an important role in our understanding of the function of the basal ganglia in behavior more broadly. In this review we explore more recent experiments that extend the role of the substantia nigra pars reticulata from a simple gate for eye movements to include a role in cognitive processes for eye movements. We review recent evidence suggesting that basal ganglia nuclei beyond the substantia nigra may also play a role in eye movements and the cognitive events leading up to the production of eye movements. We close by pointing out some unresolved questions in our understanding of the relationship of basal ganglia nuclei and eye movements.

Activity in descending dopaminergic neurons represents but is not required for leg movements in the fruit fly Drosophila.

Modulatory descending neurons (DNs) that link the brain to body motor circuits, including dopaminergic DNs (DA-DNs), are thought to contribute to the flexible control of behavior. Dopamine elicits locomotor-like outputs and influences neuronal excitability in isolated body motor circuits over tens of seconds to minutes, but it remains unknown how and over what time scale DA-DN activity relates to movement in behaving animals. To address this question, we identified DA-DNs in the Drosophila brain and developed an electrophysiological preparation to record and manipulate the activity of these cells during behavior. We find that DA-DN spike rates are rapidly modulated during a subset of leg movements and scale with the total speed of ongoing leg movements, whether occurring spontaneously or in response to stimuli. However, activating DA-DNs does not elicit leg movements in intact flies, nor do acute bidirectional manipulations of DA-DN activity affect the probability or speed of leg movements over a time scale of seconds to minutes. Our findings indicate that in the context of intact descending control, changes in DA-DN activity are not sufficient to influence ongoing leg movements and open the door to studies investigating how these cells interact with other descending and local neuromodulatory inputs to influence body motor output.

Locomotor head movements and semicircular canal morphology in primates.

Animal locomotion causes head rotations, which are detected by the semicircular canals of the inner ear. Morphologic features of the canals influence rotational sensitivity, and so it is hypothesized that locomotion and canal morphology are functionally related. Most prior research has compared subjective assessments of animal "agility" with a single determinant of rotational sensitivity: the mean canal radius of curvature (R). In fact, the paired variables of R and body mass are correlated with agility and have been used to infer locomotion in extinct species. To refine models of canal functional morphology and to improve locomotor inferences for extinct species, we compare 3D vector measurements of head rotation during locomotion with 3D vector measures of canal sensitivity. Contrary to the predictions of conventional models that are based upon R, we find that axes of rapid head rotation are not aligned with axes of either high or low sensitivity. Instead, animals with fast head rotations have similar sensitivities in all directions, which they achieve by orienting the three canals of each ear orthogonally (i.e., along planes at 90° angles to one another). The extent to which the canal configuration approaches orthogonality is correlated with rotational head speed independent of body mass and phylogeny, whereas R is not.

A pathway in primate brain for internal monitoring of movements.

It is essential to keep track of the movements we make, and one way to do that is to monitor correlates, or corollary discharges, of neuronal movement commands. We hypothesized that a previously identified pathway from brainstem to frontal cortex might carry corollary discharge signals. We found that neuronal activity in this pathway encodes upcoming eye movements and that inactivating the pathway impairs sequential eye movements consistent with loss of corollary discharge without affecting single eye movements. These results identify a pathway in the brain of the primate Macaca mulatta that conveys corollary discharge signals.

Accounting for Posttraumatic Stress Disorder Symptom Severity With Pre- and Posttrauma Measures: A Longitudinal Study of Older Adults.

Using data from a longitudinal study of community-dwelling older adults, we analyzed the most extensive set of known correlates of PTSD symptoms obtained from a single sample to examine the measures' independent and combined utility in accounting for PTSD symptom severity. Fifteen measures identified as PTSD risk factors in published meta-analyses and 12 theoretically and empirically supported individual difference and health-related measures were included. Individual difference measures assessed after the trauma, including insecure attachment and factors related to the current trauma memory, such as self-rated severity, event centrality, frequency of involuntary recall, and physical reactions to the memory, accounted for symptom severity better than measures of pre-trauma factors. In an analysis restricted to prospective measures assessed before the trauma, the total variance explained decreased from 56% to 16%. Results support a model of PTSD in which characteristics of the current trauma memory promote the development and maintenance of PTSD symptoms.