Improved perioperative narcotic usage patterns in patients undergoing robotic-assisted compared to manual total hip arthroplasty.

Background: Robot-assisted total hip arthroplasty (RA-THA) improves accuracy in achieving the planned acetabular cup positioning compared to conventional manual THA (mTHA), but optimal dosage for peri-RA-THA and mTHA pain relief remains unclear. This study aimed to compare pain control with opioids between patients undergoing direct anterior approach THA with the use of a novel, fluoroscopic-assisted RA-THA system compared to opioid consumption associated with fluoroscopic-assisted, manual technique.

Methods: Retrospective cohort analysis was performed on a consecutive series of patients who received mTHA and fluoroscopy-based RA-THA.

Activation and expansion of presynaptic signaling foci drives presynaptic homeostatic plasticity.

Presynaptic homeostatic plasticity (PHP) adaptively regulates synaptic transmission in health and disease. Despite identification of numerous genes that are essential for PHP, we lack a dynamic framework to explain how PHP is initiated, potentiated, and limited to achieve precise control of vesicle fusion. Here, utilizing both mice and Drosophila, we demonstrate that PHP progresses through the assembly and physical expansion of presynaptic signaling foci where activated integrins biochemically converge with trans-synaptic Semaphorin2b/PlexinB signaling.

NMDAR-dependent presynaptic homeostasis in adult hippocampus: Synapse growth and cross-modal inhibitory plasticity.

Homeostatic plasticity (HP) encompasses a suite of compensatory physiological processes that counteract neuronal perturbations, enabling brain resilience. Currently, we lack a complete description of the homeostatic processes that operate within the mammalian brain. Here, we demonstrate that acute, partial AMPAR-specific antagonism induces potentiation of presynaptic neurotransmitter release in adult hippocampus, a form of compensatory plasticity that is consistent with the expression of presynaptic homeostatic plasticity (PHP) documented at peripheral synapses.

SVIP is a molecular determinant of lysosomal dynamic stability, neurodegeneration and lifespan.

Missense mutations in Valosin-Containing Protein (VCP) are linked to diverse degenerative diseases including IBMPFD, amyotrophic lateral sclerosis (ALS), muscular dystrophy and Parkinson's disease. Here, we characterize a VCP-binding co-factor (SVIP) that specifically recruits VCP to lysosomes. SVIP is essential for lysosomal dynamic stability and autophagosomal-lysosomal fusion.

Homeostatic plasticity fails at the intersection of autism-gene mutations and a novel class of common genetic modifiers.

We identify a set of common phenotypic modifiers that interact with five independent autism gene orthologs (, , , , ) causing a common failure of presynaptic homeostatic plasticity (PHP) in . Heterozygous null mutations in each autism gene are demonstrated to have normal baseline neurotransmission and PHP. However, PHP is sensitized and rendered prone to failure.

Presynaptic Homeostasis Opposes Disease Progression in Mouse Models of ALS-Like Degeneration: Evidence for Homeostatic Neuroprotection.

Progressive synapse loss is an inevitable and insidious part of age-related neurodegenerative disease. Typically, synapse loss precedes symptoms of cognitive and motor decline. This suggests the existence of compensatory mechanisms that can temporarily counteract the effects of ongoing neurodegeneration.

Not Fade Away: Mechanisms of Neuronal ATP Homeostasis.

In this issue of Neuron, Ashrafi et al. (2020) identify a feedforward signaling mechanism that couples neuronal activity to the homeostatic maintenance of axonal and synaptic ATP production. This mechanism is achieved via changes in cytoplasmic calcium and activation of brain-specific, mitochondrial MICU3.

Epigenetic Signaling in Glia Controls Presynaptic Homeostatic Plasticity.

Epigenetic gene regulation shapes neuronal fate in the embryonic nervous system. Post-embryonically, epigenetic signaling within neurons has been associated with impaired learning, autism, ataxia, and schizophrenia. Epigenetic factors are also enriched in glial cells.

Target-wide Induction and Synapse Type-Specific Robustness of Presynaptic Homeostasis.

Presynaptic homeostatic plasticity (PHP) is an evolutionarily conserved form of adaptive neuromodulation and is observed at both central and peripheral synapses. In this work, we make several fundamental advances by interrogating the synapse specificity of PHP. We define how PHP remains robust to acute versus long-term neurotransmitter receptor perturbation.

Evolution of Mechanisms that Control Mating in Drosophila Males.

Genetically wired neural mechanisms inhibit mating between species because even naive animals rarely mate with other species. These mechanisms can evolve through changes in expression or function of key genes in sensory pathways or central circuits. Gr32a is a gustatory chemoreceptor that, in D.

Dual separable feedback systems govern firing rate homeostasis.

Firing rate homeostasis (FRH) stabilizes neural activity. A pervasive and intuitive theory argues that a single variable, calcium, is detected and stabilized through regulatory feedback. A prediction is that ion channel gene mutations with equivalent effects on neuronal excitability should invoke the same homeostatic response.

Dystrobrevin is required postsynaptically for homeostatic potentiation at the Drosophila NMJ.

Evolutionarily conserved homeostatic systems have been shown to modulate synaptic efficiency at the neuromuscular junctions of organisms. While advances have been made in identifying molecules that function presynaptically during homeostasis, limited information is currently available on how postsynaptic alterations affect presynaptic function. We previously identified a role for postsynaptic Dystrophin in the maintenance of evoked neurotransmitter release.

Molecular mechanisms that stabilize short term synaptic plasticity during presynaptic homeostatic plasticity.

Presynaptic homeostatic plasticity (PHP) compensates for impaired postsynaptic neurotransmitter receptor function through a rapid, persistent adjustment of neurotransmitter release, an effect that can exceed 200%. An unexplained property of PHP is the preservation of short-term plasticity (STP), thereby stabilizing activity-dependent synaptic information transfer. We demonstrate that the dramatic potentiation of presynaptic release during PHP is achieved while simultaneously maintaining a constant ratio of primed to super-primed synaptic vesicles, thereby preserving STP.

Molecular Interface of Neuronal Innate Immunity, Synaptic Vesicle Stabilization, and Presynaptic Homeostatic Plasticity.

We define a homeostatic function for innate immune signaling within neurons. A genetic analysis of the innate immune signaling genes IMD, IKKβ, Tak1, and Relish demonstrates that each is essential for presynaptic homeostatic plasticity (PHP). Subsequent analyses define how the rapid induction of PHP (occurring in seconds) can be coordinated with the life-long maintenance of PHP, a time course that is conserved from invertebrates to mammals.

The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.

Although gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, schizophrenia, and Tourette disorder, has accelerated, resulting in a large number of molecular clues, it has proven difficult to generate specific hypotheses without the corresponding datasets at the protein complex and functional pathway level. Here, we describe one path forward-an initiative aimed at mapping the physical and genetic interaction networks of these conditions and then using these maps to connect the genomic data to neurobiology and, ultimately, the clinic. These efforts will include a team of geneticists, structural biologists, neurobiologists, systems biologists, and clinicians, leveraging a wide array of experimental approaches and creating a collaborative infrastructure necessary for long-term investigation.

A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity.

Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown.

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease.

Engineering a light-activated caspase-3 for precise ablation of neurons in vivo.

The circuitry of the brain is characterized by cell heterogeneity, sprawling cellular anatomy, and astonishingly complex patterns of connectivity. Determining how complex neural circuits control behavior is a major challenge that is often approached using surgical, chemical, or transgenic approaches to ablate neurons. However, all these approaches suffer from a lack of precise spatial and temporal control.

Composition and Control of a Deg/ENaC Channel during Presynaptic Homeostatic Plasticity.

The homeostatic control of presynaptic neurotransmitter release stabilizes information transfer at synaptic connections in the nervous system of organisms ranging from insect to human. Presynaptic homeostatic signaling centers upon the regulated membrane insertion of an amiloride-sensitive degenerin/epithelial sodium (Deg/ENaC) channel. Elucidating the subunit composition of this channel is an essential step toward defining the underlying mechanisms of presynaptic homeostatic plasticity (PHP).

MCTP is an ER-resident calcium sensor that stabilizes synaptic transmission and homeostatic plasticity.

Presynaptic homeostatic plasticity (PHP) controls synaptic transmission in organisms from to human and is hypothesized to be relevant to the cause of human disease. However, the underlying molecular mechanisms of PHP are just emerging and direct disease associations remain obscure. In a forward genetic screen for mutations that block PHP we identified (Multiple C2 Domain Proteins with Two Transmembrane Regions).

The Global Challenge in Neuroscience Education and Training: The MBL Perspective.

The greatest challenge in moving neuroscience research forward in the 21st century is recruiting, training, and retaining the brightest, rigorous, and most diverse scientists. The MBL research training courses Neurobiology and Neural Systems & Behavior, and the Summer Program in Neuroscience, Excellence, and Success provide a model for full immersion, discovery-based training while enhancing cultural, geographic, and racial diversity.

α2δ-3 Is Required for Rapid Transsynaptic Homeostatic Signaling.

The homeostatic modulation of neurotransmitter release, termed presynaptic homeostatic potentiation (PHP), is a fundamental type of neuromodulation, conserved from Drosophila to humans, that stabilizes information transfer at synaptic connections throughout the nervous system. Here, we demonstrate that α2δ-3, an auxiliary subunit of the presynaptic calcium channel, is required for PHP. The α2δ gene family has been linked to chronic pain, epilepsy, autism, and the action of two psychiatric drugs: gabapentin and pregabalin.

The Innate Immune Receptor PGRP-LC Controls Presynaptic Homeostatic Plasticity.

It is now appreciated that the brain is immunologically active. Highly conserved innate immune signaling responds to pathogen invasion and injury and promotes structural refinement of neural circuitry. However, it remains generally unknown whether innate immune signaling has a function during the day-to-day regulation of neural function in the absence of pathogens and irrespective of cellular damage or developmental change.

VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo.

Lysosomes are classically viewed as vesicular structures to which cargos are delivered for degradation. Here, we identify a network of dynamic, tubular lysosomes that extends throughout Drosophila muscle, in vivo. Live imaging reveals that autophagosomes merge with tubular lysosomes and that lysosomal membranes undergo extension, retraction, fusion and fission.

Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance.

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved.