Federalism: Deference Meets Delegation: Which Is the Most Dangerous Branch

The following is a transcript of a 2016 Federalist Society panel entitled Federalism: Deference Meets Delegation: Which is the Most Dangerous Branch? The panel originally occurred on November 12, 2015, during the National Lawyers Convention in Washington, D.C. The panelists were: C. Boyden Gray, Attorney at Boyden, Gray and Associates and former U.S. Ambassador to the European Union; David B. Rivkin Jr., Partner at BakerHostetler; Neal K. Katyal, Attorney at Hogan Lovells and former acting U.S. Solicitor General; and John C. Eastman, Henry Salvatori Professor of Law & Community Service at Chapman University School of Law. The moderator was the Honorable Judge Brett Kavanaugh of the U.S. Court of Appeals, D.C. Circuit

Automated whole-cell patch-clamp electrophysiology of neurons in vivo

Whole-cell patch-clamp electrophysiology of neurons is a gold-standard technique for high-fidelity analysis of the biophysical mechanisms of neural computation and pathology, but it requires great skill to perform. We have developed a robot that automatically performs patch clamping in vivo, algorithmically detecting cells by analyzing the temporal sequence of electrode impedance changes. We demonstrate good yield, throughput and quality of automated intracellular recording in mouse cortex and hippocampus.National Institutes of Health (U.S.) (NIH EUREKA Award program (1R01NS075421))National Institutes of Health (U.S.) ((NIH) Director′s New Innovator Award (DP2OD002002)National Science Foundation (U.S.) ((NSF) CAREER award (CBET 1053233))New York Stem Cell Foundation (Robertson Neuroscience Award)Dr. Gerald Burnett and Marjorie BurnettNational Science Foundation (U.S.) (grant CISE 1110947)National Science Foundation (U.S.) (grant EHR 0965945)American Heart Association (10GRNT4430029

In vivo robotics: the automation of neuroscience and other intact-system biological fields

Robotic and automation technologies have played a huge role in in vitro biological science, having proved critical for scientific endeavors such as genome sequencing and high-throughput screening. Robotic and automation strategies are beginning to play a greater role in in vivo and in situ sciences, especially when it comes to the difficult in vivo experiments required for understanding the neural mechanisms of behavior and disease. In this perspective, we discuss the prospects for robotics and automation to influence neuroscientific and intact-system biology fields. We discuss how robotic innovations might be created to open up new frontiers in basic and applied neuroscience and present a concrete example with our recent automation of in vivo whole-cell patch clamp electrophysiology of neurons in the living mouse brain.National Institutes of Health (U.S.) (Single Cell Grant 1 R01 EY023173)Human Frontier Science Program (Strasbourg, France)McGovern Institute for Brain Research at MIT. Neurotechnology (MINT) ProgramMIT Media Lab ConsortiumNew York Stem Cell Foundation (Robertson Investigator Award)National Institutes of Health (U.S.) (Director's New Innovator Award 1DP2OD002002)National Institutes of Health (U.S.) (EUREKA Award 1R01GM104948)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (CAREER Award CBET 1053233)National Science Foundation (U.S.) (DMS1042134)Paul G. Allen Family Foundation (Distinguished Investigator in Neuroscience Award)Skolkovo Institute of Science and Technolog

Synthetic Physiology

Optogenetic tools are DNA-encoded molecules that, when genetically targeted to cells, enable the control of specific physiological processes within those cells through exposure to light. These tools can pinpoint how these specific processes affect the emergent properties of a complex biological system, such as a mammalian organ or even an entire animal. They can also allow control of a biological system for therapeutic or bioengineering purposes. Many of the optical control tools explored to date are single-component reagents containing a photoactive signaling domain. An interesting question is raised by comparing optogenetics to synthetic biology. In the latter, interchangeable and modular DNA-encoded parts are assembled into complex biological circuits, thus enabling sophisticated logic and computation as well as the production of biologics and reagents (1, 2). Is it possible to devise strategies for the temporally precise cell-targeted optical control of complex engineered biological computational or chemical-synthetic pathways? Such a marriage of optogenetics and synthetic biology—which one might call synthetic physiology—would open up the ability to use optogenetics to trigger and regulate engineered synthetic biology systems, which in turn could execute computational and biological programs of great complexity (3). On page 1565 of this issue, Ye et al. (4) explore such a hybrid approach to controlling a biological system, as well as the bioengineering and preclinical capabilities opened up by such an approach

Seeing the forest for the heterogeneous trees: stand-scale resource distributions emerge from tree-scale structure

Abstract. Forest ecosystem processes depend on local interactions that are modified by the spatial pattern of trees and resources. Effects of resource supplies on processes such as regeneration are increasingly well understood, yet we have few tools to compare resource heterogeneity among forests that differ in structural complexity. We used a neighborhood approach to examine understory light and nutrient availability in a well-replicated and largescale variable-retention harvesting experiment in a red pine forest in Minnesota, USA. The experiment included an unharvested control and three harvesting treatments with similar tree abundance but different patterns of retention (evenly dispersed as well as aggregated retention achieved by cutting 0.1-or 0.3-ha gaps). We measured light and soil nutrients across all treatments and mapped trees around each sample point to develop an index of neighborhood effects (NI). Field data and simulation modeling were used to test hypotheses that the mean and heterogeneity of resource availability would increase with patchiness because of greater variation in competitive environments. Our treatments dramatically altered the types and abundances of competitive neighborhoods (NI) in each stand and resulted in significantly nonlinear relationships of light, nitrogen and phosphorus availability to NI. Hence, the distribution of neighborhoods in each treatment had a significant impact on resource availability and heterogeneity. In dense control stands, neighborhood variation had little impact on resource availability, whereas in more open stands (retention treatments), it had large effects on light and modest effects on soil nutrients. Our results demonstrate that tree spatial pattern can affect resource availability and heterogeneity in explainable and predictable ways, and that neighborhood models provide a useful tool for scaling heterogeneity from the individual tree to the stand. These insights are needed to anticipate the outcomes of silvicultural manipulations and should become more holistically integrated into both basic ecological and management science

Biomass growth response to spatial pattern of variable-retention harvesting in a northern Minnesota pine ecosystem

Variable-retention harvesting (VRH) is an approach for sustaining complex structure in managed forests. A criticism of VRH is that ecological benefits may come at a cost of reduced growth of regeneration, due to competition with residual trees. However, the spatial pattern of retention, i.e., dispersed or aggregated, in VRH systems can be manipulated to minimize suppression of regeneration, and resource limitation to regeneration might be mitigated by reduction of woody shrubs. Continued growth of the residual cohort will compensate for growth reduction of regeneration, although this may differ with retention pattern. We examined aboveground whole-stand biomass growth of trees in a VRH experiment in Pinus resinosa forest in Minnesota, USA. Treatments included dispersed retention, aggregated retention, and an uncut control, as well as a shrub treatment (reduced density or ambient). We addressed the following hypotheses: (1) biomass growth of a cohort of planted pine seedlings will be highest with aggregated rather than dispersed retention, (2) biomass growth of the planted seedlings will increase with shrub reduction, and (3) biomass growth of the residual overstory will be higher with dispersed rather than aggregated retention. Aboveground biomass growth of the planted pines ranged from 0.4 kg·ha−1·yr−1 in the overstory-control–ambient-shrub treatment to 23 kg·ha−1·yr−1 in the aggregated-retention–shrub-reduction treatment. The difference between the control and the retention treatments was significant (P 100% increase) with shrub reduction (P = 0.001), supporting our second hypothesis. Biomass growth of residual trees ranged from 2404 kg·ha−1·yr−1 in the uncut-control–ambient-shrub treatment to 1043 kg·ha−1·yr−1 in the aggregated-retention–shrub-reduction treatment. Differences were significant between the control and retention treatments (P = 0.003), and marginally higher with dispersed vs. aggregated retention (P = 0.09), lending support to our third hypothesis. Our results suggest that managers have flexibility in application of VRH and can expect similar stand-level biomass growth of planted regeneration regardless of retention pattern, but somewhat higher stand-level biomass growth of retained trees with dispersed retention

The emerging contribution of social wasps to grape rot disease ecology

Grape sour (bunch) rot is a polymicrobial disease of vineyards that causes millions of dollars in lost revenue per year due to decreased quality of grapes and resultant wine. The disease is associated with damaged berries infected with a community of acetic acid bacteria, yeasts, and filamentous fungi that results in rotting berries with high amounts of undesirable volatile acidity. Many insect species cause the initial grape berry damage that can lead to this disease, but most studies have focused on the role of fruit flies in facilitating symptoms and vectoring the microorganisms of this disease complex. Like fruit flies, social wasps are abundant in vineyards where they feed on ripe berries and cause significant damage, while also dispersing yeasts involved in wine fermentation. Despite this, their possible role in disease facilitation and dispersal of grape rots has not been explored. We tested the hypothesis that the paper wasp Polistes dominulus could facilitate grape sour rot in the absence of other insect vectors. Using marker gene sequencing we characterized the bacterial and fungal community of wild-caught adults. We used a sterilized foraging arena to determine if these wasps transfer viable microorganisms when foraging. We then tested if wasps harboring their native microbial community, or those inoculated with sour rot, had an effect on grape sour rot incidence and severity using a laboratory foraging arena. We found that all wasps harbor some portion of the sour rot microbial community and that they have the ability to transfer viable microorganisms when foraging. Foraging by inoculated and uninoculated wasps led to an increase in berry rot disease symptom severity and incidence. Our results indicate that paper wasps can facilitate sour rot diseases in the absence of other vectors and that the mechanism of this facilitation may include both increasing host susceptibility and transmitting these microbial communities to the grapes. Social wasps are understudied but relevant players in the sour rot ecology of vineyards

Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons

The dopamine systems of the brain powerfully influence movement and motivation. We demonstrate that striatonigral fibers originating in striosomes form highly unusual bouquet-like arborizations that target bundles of ventrally extending dopamine-containing dendrites and clusters of their parent nigral cell bodies. Retrograde tracing showed that these clustered cell bodies in turn project to the striatum as part of the classic nigrostriatal pathway. Thus, these striosome-dendron formations, here termed "striosome-dendron bouquets," likely represent subsystems with the nigro-striato-nigral loop that are affected in human disorders including Parkinson's disease. Within the bouquets, expansion microscopy resolved many individual striosomal fibers tightly intertwined with the dopamine-containing dendrites and also with afferents labeled by glutamatergic, GABAergic, and cholinergic markers and markers for astrocytic cells and fibers and connexin 43 puncta. We suggest that the striosome-dendron bouquets form specialized integrative units within the dopamine-containing nigral system. Given evidence that striosomes receive input from cortical regions related to the control of mood and motivation and that they link functionally to reinforcement and decision-making, the striosome-dendron bouquets could be critical to dopamine-related function in health and disease

Hearing the light: neural and perceptual encoding of optogenetic stimulation in the central auditory pathway

Optogenetics provides a means to dissect the organization and function of neural circuits. Optogenetics also offers the translational promise of restoring sensation, enabling movement or supplanting abnormal activity patterns in pathological brain circuits. However, the inherent sluggishness of evoked photocurrents in conventional channelrhodopsins has hampered the development of optoprostheses that adequately mimic the rate and timing of natural spike patterning. Here, we explore the feasibility and limitations of a central auditory optoprosthesis by photoactivating mouse auditory midbrain neurons that either express channelrhodopsin-2 (ChR2) or Chronos, a channelrhodopsin with ultra-fast channel kinetics. Chronos-mediated spike fidelity surpassed ChR2 and natural acoustic stimulation to support a superior code for the detection and discrimination of rapid pulse trains. Interestingly, this midbrain coding advantage did not translate to a perceptual advantage, as behavioral detection of midbrain activation was equivalent with both opsins. Auditory cortex recordings revealed that the precisely synchronized midbrain responses had been converted to a simplified rate code that was indistinguishable between opsins and less robust overall than acoustic stimulation. These findings demonstrate the temporal coding benefits that can be realized with next-generation channelrhodopsins, but also highlight the challenge of inducing variegated patterns of forebrain spiking activity that support adaptive perception and behavior

A direct-to-drive neural data acquisition system

Driven by the increasing channel count of neural probes, there is much effort being directed to creating increasingly scalable electrophysiology data acquisition (DAQ) systems. However, all such systems still rely on personal computers for data storage, and thus are limited by the bandwidth and cost of the computers, especially as the scale of recording increases. Here we present a novel architecture in which a digital processor receives data from an analog-to-digital converter, and writes that data directly to hard drives, without the need for a personal computer to serve as an intermediary in the DAQ process. This minimalist architecture may support exceptionally high data throughput, without incurring costs to support unnecessary hardware and overhead associated with personal computers, thus facilitating scaling of electrophysiological recording in the future.National Institutes of Health (U.S.) (Grant 1DP1NS087724)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Institutes of Health (U.S.) (Grant 2R44NS070453)National Institutes of Health (U.S.) (Grant R43MH101943)New York Stem Cell FoundationPaul Allen FoundationMassachusetts Institute of Technology. Media LaboratoryGoogle (Firm)United States. Defense Advanced Research Projects Agency (HR0011-14-2-0004)Hertz Foundation (Myhrvold Family Fellowship