Neuronal identity control at the resolution of a single transcription factor isoform.

The brain exhibits remarkable neuronal diversity which is critical for its functional integrity. From the sheer number of cell types emerging from extensive transcriptional, morphological, and connectome datasets, the question arises of how the brain is capable of generating so many unique identities. 'Terminal selectors' are transcription factors hypothesized to determine the final identity characteristics in post-mitotic cells.

Morphology and synapse topography optimize linear encoding of synapse numbers in looming responsive descending neurons.

Synapses are often precisely organized on dendritic arbors, yet the role of synaptic topography in dendritic integration remains poorly understood. Utilizing electron microscopy (EM) connectomics we investigate synaptic topography in looming circuits, focusing on retinotopically tuned visual projection neurons (VPNs) that synapse onto descending neurons (DNs). Synapses of a given VPN type project to non-overlapping regions on DN dendrites.

A Miniature Ultrasound Source for Neural Modulation.

This work describes a unique ultrasound (US) exposure system designed to create very localized ( [Formula: see text]) sound fields at operating frequencies that are currently being used for preclinical US neuromodulation. This system can expose small clusters of neuronal tissue, such as cell cultures or intact brain structures in target animal models, opening up opportunities to examine possible mechanisms of action. We modified a dental descaler and drove it at a resonance frequency of 96 kHz, well above its nominal operating point of 28 kHz.

Azimuthal invariance to looming stimuli in the Drosophila giant fiber escape circuit.

Spatially invariant feature detection is a property of many visual systems that rely on visual information provided by two eyes. However, how information across both eyes is integrated for invariant feature detection is not fully understood. Here, we investigated spatial invariance of looming responses in descending neurons (DNs) of Drosophila melanogaster.

Astrocyte development-More questions than answers.

The past 15-20 years has seen a remarkable shift in our understanding of astrocyte contributions to central nervous system (CNS) function. Astrocytes have emerged from the shadows of neuroscience and are now recognized as key elements in a broad array of CNS functions. Astrocytes comprise a substantial fraction of cells in the human CNS.

Feature encoding: How back-to-front motion guides the polite fly.

Motion of a visual image from back-to-front across a visual field can provide an early-stage cue for impending collisions. A new study reveals visual feature encoding neurons that drive behavioral responses to back-to-front motion in the fly Drosophila melanogaster.

An optogenetics device with smartphone video capture to introduce neurotechnology and systems neuroscience to high school students.

Although neurotechnology careers are on the rise, and neuroscience curriculums have significantly grown at the undergraduate and graduate levels, increasing neuroscience and neurotechnology exposure in high school curricula has been an ongoing challenge. This is due, in part, to difficulties in converting cutting-edge neuroscience research into hands-on activities that are accessible for high school students and affordable for high school educators. Here, we describe and characterize a low-cost, easy-to-construct device to enable students to record rapid Drosophila melanogaster (fruit fly) behaviors during optogenetics experiments.

Regional Neurodegeneration : The Protective Role of Neural Activity.

Traumatic brain injury is a devastating public health problem, the eighth leading cause of death across the world. To improve our understanding of how injury at the cellular scale affects neural circuit function, we developed a protocol to precisely injure individual neurons within an neural network. We used high speed calcium imaging to estimate alterations in neural activity and connectivity that occur followed targeted microtrauma.

Habituation Learning Is a Widely Affected Mechanism in Drosophila Models of Intellectual Disability and Autism Spectrum Disorders.

Background: Although habituation is one of the most ancient and fundamental forms of learning, its regulators and its relevance for human disease are poorly understood.

Methods: We manipulated the orthologs of 286 genes implicated in intellectual disability (ID) with or without comorbid autism spectrum disorder (ASD) specifically in Drosophila neurons, and we tested these models in light-off jump habituation. We dissected neuronal substrates underlying the identified habituation deficits and integrated genotype-phenotype annotations, gene ontologies, and interaction networks to determine the clinical features and molecular processes that are associated with habituation deficits.

Neural Basis for Looming Size and Velocity Encoding in the Drosophila Giant Fiber Escape Pathway.

Identified neuron classes in vertebrate cortical [1-4] and subcortical [5-8] areas and invertebrate peripheral [9-11] and central [12-14] brain neuropils encode specific visual features of a panorama. How downstream neurons integrate these features to control vital behaviors, like escape, is unclear [15]. In Drosophila, the timing of a single spike in the giant fiber (GF) descending neuron [16-18] determines whether a fly uses a short or long takeoff when escaping a looming predator [13].

A novel assay to evaluate action selection in escape behavior.

Background: How experience and individuality shape action selection remains a major question in neuroscience. Visually-evoked escape behavior within Drosophila melanogaster provides a robust model to study these mechanisms within neural circuits but requires novel assays to circumvent limitations of current behavior assays.

Method: Here we describe and characterize a simple, low to moderate cost, and flexible assay for studying visually-evoked escape responses in tethered flies.

Feature Integration Drives Probabilistic Behavior in the Drosophila Escape Response.

Animals rely on dedicated sensory circuits to extract and encode environmental features. How individual neurons integrate and translate these features into behavioral responses remains a major question. Here, we identify a visual projection neuron type that conveys predator approach information to the Drosophila giant fiber (GF) escape circuit.

A spike-timing mechanism for action selection.

We discovered a bimodal behavior in the genetically tractable organism Drosophila melanogaster that allowed us to directly probe the neural mechanisms of an action selection process. When confronted by a predator-mimicking looming stimulus, a fly responds with either a long-duration escape behavior sequence that initiates stable flight or a distinct, short-duration sequence that sacrifices flight stability for speed. Intracellular recording of the descending giant fiber (GF) interneuron during head-fixed escape revealed that GF spike timing relative to parallel circuits for escape actions determined which of the two behavioral responses was elicited.

Brain injury-induced proteolysis is reduced in a novel calpastatin-overexpressing transgenic mouse.

The calpain family of calcium-dependent proteases has been implicated in a variety of diseases and neurodegenerative pathologies. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components and membrane receptors, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains. Pharmacological and gene-knockout strategies have targeted calpains to determine their contribution to neurodegenerative pathology; however, limitations associated with treatment paradigms, drug specificity, and genetic disruptions have produced inconsistent results and complicated interpretation.

In vitro stretch injury induces time- and severity-dependent alterations of STEP phosphorylation and proteolysis in neurons.

Striatal-enriched tyrosine phosphatase (STEP) has been identified as a component of physiological and pathophysiological signaling pathways mediated by N-methyl-d-aspartate (NMDA) receptor/calcineurin/calpain activation. Activation of these pathways produces a subsequent change in STEP isoform expression or activation via dephosphorylation. In this study, we evaluated changes in STEP phosphorylation and proteolysis in dissociated cortical neurons after sublethal and lethal mechanical injury using an in vitro stretch injury device.

Mechanisms of calpain mediated proteolysis of voltage gated sodium channel α-subunits following in vitro dynamic stretch injury.

Although enhanced calpain activity is well documented after traumatic brain injury (TBI), the pathways targeting specific substrate proteolysis are less defined. Our past work demonstrated that calpain cleaves voltage gated sodium channel (NaCh) α-subunits in an in vitro TBI model. In this study, we investigated the pathways leading to NaCh cleavage utilizing our previously characterized in vitro TBI model, and determined the location of calpain activation within neuronal regions following stretch injury to micropatterned cultures.

Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit.

Alterations in the expression, molecular composition, and localization of voltage-gated sodium channels play major roles in a broad range of neurological disorders. Recent evidence identifies sodium channel proteolysis as a key early event after ischemia and traumatic brain injury, further expanding the role of the sodium channel in neurological diseases. In this study, we investigate the protease responsible for proteolytic cleavage of voltage-gated sodium channels (NaChs).

Linking impact to cellular and molecular sequelae of CNS injury: modeling in vivo complexity with in vitro simplicity.

Traumatic brain injury (TBI) represents one of most common disorders to the central nervous system (CNS). Despite significant efforts, though, an effective clinical treatment for TBI is not yet available. The complexity of human TBI is modeled with a broad group of experimental models, with each model matching some aspect of the human condition.