Publications by authors named "Brett Mensh"

Dance plays a vital role in human societies across time and culture, with different communities having invented different systems for artistic expression through movement (genres). Differences between genres can be described by experts in words and movements, but these descriptions can only be appreciated by people with certain background abilities. Existing dance notation schemes could be applied to describe genre-differences, however they fall substantially short of being able to capture the important details of movement across a wide spectrum of genres.

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Objective: Spinal cord injury (SCI) damages synaptic connections between corticospinal axons and motoneurons of many muscles, resulting in devastating paralysis. We hypothesized that strengthening corticospinal-motoneuronal synapses at multiple spinal cord levels through Hebbian plasticity (i.e.

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Article Synopsis
  • - Animals use their movements to track where they are in space, but it’s unclear how this works in older brain structures compared to the mammalian brain.
  • - In a study with larval zebrafish in a virtual swimming environment, researchers found that the fish could remember their previous locations and swim back to them after being moved involuntarily.
  • - The study identified a network in the brain that helps remember these locations and influences movement, showing that even ancient brain regions in vertebrates play a crucial role in integrating motion and controlling behavior.
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Brain function is mediated by the physiological coordination of a vast, intricately connected network of molecular and cellular components. The physiological properties of neural network components can be quantified with high throughput. The ability to assess many animals per study has been critical in relating physiological properties to behavior.

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Folded proteins are assumed to be built upon fixed scaffolds of secondary structure, α-helices and β-sheets. Experimentally determined structures of >58,000 non-redundant proteins support this assumption, though it has recently been challenged by ~100 fold-switching proteins. Though ostensibly rare, these proteins raise the question of how many uncharacterized proteins have shapeshifting-rather than fixed-secondary structures.

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In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907).

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Article Synopsis
  • - The brain's primary role is to select actions that enhance an animal's survival and reproduction, adapting based on environmental conditions, bodily needs, and past experiences.
  • - Understanding the neural interactions that drive behavior requires examining processes at various spatial levels, from individual synapses to whole brain networks.
  • - Larval zebrafish serve as an effective research model due to their size and transparency, facilitating advanced techniques that reveal the mechanisms behind behavioral states, with findings being compared to similar research in mammals.
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Adaptive movements are critical for animal survival. To guide future actions, the brain monitors various outcomes, including achievement of movement and appetitive goals. The nature of these outcome signals and their neuronal and network realization in the motor cortex (M1), which directs skilled movements, is largely unknown.

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In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor ($\alpha_1$-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n=18,547) and three cohorts with pneumonia (n=400,907).

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The motor cortex controls skilled arm movement by sending temporal patterns of activity to lower motor centres. Local cortical dynamics are thought to shape these patterns throughout movement execution. External inputs have been implicated in setting the initial state of the motor cortex, but they may also have a pattern-generating role.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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The thalamus is the central communication hub of the forebrain and provides the cerebral cortex with inputs from sensory organs, subcortical systems and the cortex itself. Multiple thalamic regions send convergent information to each cortical region, but the organizational logic of thalamic projections has remained elusive. Through comprehensive transcriptional analyses of retrogradely labeled thalamic neurons in adult mice, we identify three major profiles of thalamic pathways.

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Genetically encoded voltage indicators (GEVIs) enable monitoring of neuronal activity at high spatial and temporal resolution. However, the utility of existing GEVIs has been limited by the brightness and photostability of fluorescent proteins and rhodopsins. We engineered a GEVI, called Voltron, that uses bright and photostable synthetic dyes instead of protein-based fluorophores, thereby extending the number of neurons imaged simultaneously in vivo by a factor of 10 and enabling imaging for significantly longer durations relative to existing GEVIs.

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Article Synopsis
  • Animals often give up and become passive after repeated behavioral failures, which can help them conserve energy or regroup.
  • In a study with larval zebrafish in virtual reality, visual feedback was controlled to induce swim failures, leading to periods of passivity after several unsuccessful attempts.
  • Research showed that noradrenergic neurons and radial astrocytes in the brain respond to these failures; specifically, astrocytes accumulate evidence of failed attempts and influence the decision to stop swimming.
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Cognitive phenotypes characterize our memories, beliefs, skills, and preferences, and arise from our ancestral, developmental, and experiential histories. These histories are written into our brain structure through the building and modification of various brain circuits. Connectal coding, by way of analogy with neural coding, is the art, study, and practice of identifying the network structures that link cognitive phenomena to individual histories.

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To effortlessly complete an intentional movement, the brain needs feedback from the body regarding the movement's progress. This largely nonconscious kinesthetic sense helps the brain to learn relationships between motor commands and outcomes to correct movement errors. Prosthetic systems for restoring function have predominantly focused on controlling motorized joint movement.

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Behavior has molecular, cellular, and circuit determinants. However, because many proteins are broadly expressed, their acute manipulation within defined cells has been difficult. Here, we combined the speed and molecular specificity of pharmacology with the cell type specificity of genetic tools.

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To execute accurate movements, animals must continuously adapt their behavior to changes in their bodies and environments. Animals can learn changes in the relationship between their locomotor commands and the resulting distance moved, then adjust command strength to achieve a desired travel distance. It is largely unknown which circuits implement this form of motor learning, or how.

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Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive interactions is still an open question.

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Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons. Accordingly, the myelin observed in neocortical gray matter is thought to mostly ensheath excitatory axons connecting to subcortical regions and distant cortical areas. Using independent analyses of light and electron microscopy data from mouse neocortex, we show that a surprisingly large fraction of cortical myelin (half the myelin in layer 2/3 and a quarter in layer 4) ensheathes axons of inhibitory neurons, specifically of parvalbumin-positive basket cells.

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Emotional processes are central to behavior, yet their deeply subjective nature has been a challenge for neuroscientific study as well as for psychiatric diagnosis. Here we explore the relationships between subjective feelings and their underlying brain circuits from a computational perspective. We apply recent insights from systems neuroscience-approaching subjective behavior as the result of mental computations instantiated in the brain-to the study of emotions.

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Understanding the functions of a brain region requires knowing the neural representations of its myriad inputs, local neurons and outputs. Primary visual cortex (V1) has long been thought to compute visual orientation from untuned thalamic inputs, but very few thalamic inputs have been measured in any mammal. We determined the response properties of ∼ 28,000 thalamic boutons and ∼ 4,000 cortical neurons in layers 1-5 of awake mouse V1.

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