Strategies for recovering exact structure of neural circuits with broadly targeted fluorescent connectivity probes

We present a framework for reconstructing structure of complete neural circuits
in the brain using collections of independent measurements of connectivity
performed with existing anatomical or functional fluorescent probes, and
designed to provide complementary information about neural circuit’s structure
by targeting slightly different its parts either in deterministic or stochastic
succession. We discuss specific implementation of this procedure using
synaptic fluorescent marker GRASP and Cre/Lox system Brainbow to collect
ensemble of observations of the sets of synapses between stochastically labeled
samples of neurons. By representing such measurements mathematically as
weak constraints on circuit’s connectivity matrix and by solving a constrained
optimization problem, we are able to exactly deduce the wiring diagram in C.
Elegans in an in-silico experiment from only ~10,000 measurements. This
offers possibility for routinely reconstructing complete connectivity in smaller
organisms, such as C. Elegans, using exclusively light microscopy instruments
over the span of single weeks

A high resolution spatiotemporal model for in-vehicle black carbon exposure : quantifying the in-vehicle exposure reduction due to the Euro 5 particulate matter standard legislation

Several studies have shown that a significant amount of daily air pollution exposure is inhaled during trips. In this study, car drivers assessed their own black carbon exposure under real-life conditions (223 h of data from 2013). The spatiotemporal exposure of the car drivers is modeled using a data science approach, referred to as microscopic land-use regression (mu LUR). In-vehicle exposure is highly dynamical and is strongly related to the local traffic dynamics. An extensive set of potential covariates was used to model the in-vehicle black carbon exposure in a temporal resolution of 10 s. Traffic was retrieved directly from traffic databases and indirectly by attributing the trips through a noise map as an alternative traffic source. Modeling by generalized additive models (GAM) shows non-linear effects for meteorology and diurnal traffic patterns. A fitted diurnal pattern explains indirectly the complex diurnal variability of the exposure due to the non-linear interaction between traffic density and distance to the preceding vehicles. Comparing the strength of direct traffic attribution and indirect noise map-based traffic attribution reveals the potential of noise maps as a proxy for traffic-related air pollution exposure. An external validation, based on a dataset gathered in 2010-2011, quantifies the exposure reduction inside the vehicles at 33% (mean) and 50% (median). The EU PM Euro 5 PM emission standard (in force since 2009) explains the largest part of the discrepancy between the measurement campaign in 2013 and the validation dataset. The mu LUR methodology provides a high resolution, route-sensitive, seasonal and meteorology-sensitive personal exposure estimate for epidemiologists and policy makers

FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch.

Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans

The search for novel analgesics: re-examining spinal cord circuits with new tools

In this perspective, we propose the absence of detailed information regarding spinal cord circuits that process sensory information remains a major barrier to advancing analgesia. We highlight recent advances showing that functionally discrete populations of neurons in the spinal cord dorsal horn play distinct roles in processing sensory information. We then discuss new molecular, electrophysiological, and optogenetic techniques that can be employed to understand how dorsal horn circuits process tactile and nociceptive information. We believe this information can drive the development of entirely new classes of pharmacotherapies that target key elements in spinal circuits to selectively modify sensory function and blunt pain

Clafer: Lightweight Modeling of Structure, Behaviour, and Variability

Embedded software is growing fast in size and complexity, leading to intimate mixture of complex architectures and complex control. Consequently, software specification requires modeling both structures and behaviour of systems. Unfortunately, existing languages do not integrate these aspects well, usually prioritizing one of them. It is common to develop a separate language for each of these facets. In this paper, we contribute Clafer: a small language that attempts to tackle this challenge. It combines rich structural modeling with state of the art behavioural formalisms. We are not aware of any other modeling language that seamlessly combines these facets common to system and software modeling. We show how Clafer, in a single unified syntax and semantics, allows capturing feature models (variability), component models, discrete control models (automata) and variability encompassing all these aspects. The language is built on top of first order logic with quantifiers over basic entities (for modeling structures) combined with linear temporal logic (for modeling behaviour). On top of this semantic foundation we build a simple but expressive syntax, enriched with carefully selected syntactic expansions that cover hierarchical modeling, associations, automata, scenarios, and Dwyer's property patterns. We evaluate Clafer using a power window case study, and comparing it against other notations that substantially overlap with its scope (SysML, AADL, Temporal OCL and Live Sequence Charts), discussing benefits and perils of using a single notation for the purpose

A Mechanism Linking Two Known Vulnerability Factors for Alcohol Abuse: Heightened Alcohol Stimulation and Low Striatal Dopamine D2 Receptors

Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinkingFil: Bocarsly, Miriam E.. National Institutes of Health; Estados UnidosFil: da Silva e Silva, Daniel. National Institutes of Health; Estados UnidosFil: Kolb, Vanessa. National Institutes of Health; Estados UnidosFil: Luderman, Kathryn D.. National Institutes of Health; Estados UnidosFil: Shashikiran, Sannidhi. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sibley, David R.. National Institutes of Health; Estados UnidosFil: Dobbs, Lauren K.. National Institutes of Health; Estados Unidos. University of Texas at Austin; Estados UnidosFil: Álvarez, Verónica Alicia. National Institutes of Health; Estados Unido

Arousal regulates frequency tuning in primary auditory cortex.

Changes in arousal influence cortical sensory representations, but the synaptic mechanisms underlying arousal-dependent modulation of cortical processing are unclear. Here, we use 2-photon Ca2+ imaging in the auditory cortex of awake mice to show that heightened arousal, as indexed by pupil diameter, broadens frequency-tuned activity of layer 2/3 (L2/3) pyramidal cells. Sensory representations are less sparse, and the tuning of nearby cells more similar when arousal increases. Despite the reduction in selectivity, frequency discrimination by cell ensembles improves due to a decrease in shared trial-to-trial variability. In vivo whole-cell recordings reveal that mechanisms contributing to the effects of arousal on sensory representations include state-dependent modulation of membrane potential dynamics, spontaneous firing, and tone-evoked synaptic potentials. Surprisingly, changes in short-latency tone-evoked excitatory input cannot explain the effects of arousal on the broadness of frequency-tuned output. However, we show that arousal strongly modulates a slow tone-evoked suppression of recurrent excitation underlying lateral inhibition [H. K. Kato, S. K. Asinof, J. S. Isaacson, Neuron, 95, 412-423, (2017)]. This arousal-dependent "network suppression" gates the duration of tone-evoked responses and regulates the broadness of frequency tuning. Thus, arousal can shape tuning via modulation of indirect changes in recurrent network activity

Responding to gratitude in elicited oral interaction. A taxonomy of communicative options

This study explores responses to gratitude as expressed in elicited oral interaction (mimetic-pretending open role-plays) produced by native speakers of American English. It first overviews the literature on this topic. It then presents a taxonomy of the head acts and supporting moves of the responses to gratitude instantiated in the corpus under examination, which considers their strategies and formulations. Finally, it reports on their frequency of occurrence and combinatorial options across communicative situations differing in terms of the social distance and power relationships between the interactants. The findings partly confirm what reported in the literature, but partly reveal the flexibility and adaptability of these reacting speech acts to the variable context in which they may be instantiated. On the one hand, the responses to gratitude identified tend to be encoded as simple utterances, and occasionally as complex combinations of head acts and/or supporting moves; also, their head acts show a preference for a small set of strategies and formulation types, while their supporting moves are much more varied in content and form, and thus situation-specific. On the other hand, the frequency of occurrence of the responses to gratitude, their dispersion across situations, and the range of their attested strategies and formulations are not in line with those reported in previous studies. I argue that these partly divergent findings are to be related to the different data collection and categorization procedures adopted, and the different communicative situations considered across studies. Overall, the study suggests that: responses to gratitude are a set of communicative events with fuzzy boundaries, which contains core (i.e. more prototypical) and peripheral (i.e. less prototypical) exemplars; although routinized in function, responses to gratitude are not completely conventionalized in their strategic or surface realizations; alternative research approaches may provide complementary insights into these reacting speech acts; and a higher degree of comparability across studies may be ensured if explicit pragmatic and semantic parameters are adopted in the classification of their shared object of study

Effect of pyramiding Bt and CpTI genes on resistance of cotton to Helicoverpa armigera (Lepidoptera: Noctuidae) under laboratory and field conditions

Transgenic cotton (Gossypium hirsutum L.) varieties, adapted to China, have been bred that express two genes for resistance to insects. the Cry1Ac gene from Bacillus thuringiensis (Berliner) (Bt), and a trypsin inhibitor gene from cowpea (CpTI). Effectiveness of the double gene modification in conferring resistance to cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), was studied in laboratory and field experiments. In each experiment, performance of Bt+CpTI cotton was compared with Bt cotton and to a conventional nontransgenic variety. Larval survival was lower on both types of transgenic variety, compared with the conventional cotton. Survival of first-, second-, and third-stage larvae was lower on Bt+CpTI cotton than on Bt cotton. Plant structures differed in level of resistance, and these differences were similar on Bt and Bt+CpTI cotton. Likewise, seasonal trends in level of resistance in different plant structures were similar in Bt and Bt+CpTI cotton. Both types of transgenic cotton interfered with development of sixth-stage larvae to adults, and no offspring was produced by H. armigera that fed on Bt or Bt+CpTI cotton from the sixth stage onward. First-, second-, and third-stage larvae spent significantly less time feeding on transgenic cotton than on conventional cotton, and the reduction in feeding time was significantly greater on Bt+CpTI cotton than on Bt cotton. Food conversion efficiency was lower on transgenic varieties than on conventional cotton, but there was no significant difference between Bt and Bt+CpTI cotton. In 3-yr field experimentation, bollworm densities were greatly suppressed on transgenic as compared with conventional cotton, but no significant differences between Bt and Bt+CpTI cotton were found. Overall, the results from laboratory work indicate that introduction of the CpTI gene in Bt cotton raises some components of resistance in cotton against H. armigera, but enhanced control of H. armigera under field conditions, due to expression of the CpTI gene, was not demonstrate

Construction and evaluation of a scale for creative writing.

Thesis (Ed.M.)--Boston Universit