Jeffrey Michael Hubbard

Neuroservices-Alliance

A long-held tenet of neuromuscular transmission is that calcium-dependent neurotransmitter release is mediated by N-type calcium channels in frog but P/Q-type channels in mammals. The N-type assignment in frog is based principally on pharmacological sensitivity to ω-conotoxin GVIA. Our studies show that zebrafish neuromuscular transmission is also...

Graphical Abstract Highlights d Optimized, genetically encoded botulinum neurotoxin silences synaptic output in vivo d Excitatory V2a interneurons drive high-frequency components of fast locomotion d Silencing of V2as shifts locomotor frequency downward during the slow regime In Brief Silencing of neuronal populations in moving animals remains a ch...

In the vertebrate spinal cord, cerebrospinal fluid-contacting neurons (CSF-cNs) are GABAergic neurons whose functions are only beginning to unfold. Recent evidence indicates that CSF-cNs detect local spinal bending and relay this mechanosensory feedback information to motor circuits, yet many CSF-cN targets remain unknown. Using optogenetics, patte...

Significance statement: Use-dependent fatigue accompanies many neuromuscular myasthenic syndromes, including muscle rapsyn deficiency. Here, using a rapsyn-deficient line of zebrafish, we performed paired motor neuron target muscle patch-clamp recordings to investigate the mechanisms causal to this phenomenon. Our findings indicate that the reduce...

Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated receptor 1 (TAAR1) agonism has emerged as a potential new treatment approach for schizophrenia. While...

The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of...

The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KB) during low glucose availability. Neuronal KB uptake, which does not rely on the glucose transporter 4 (GLUT4) and insulin, has shown promising clinical applications in alleviating the neurological and cognitive effects...

Background: Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the molecular motor protein complex dynein. Reduced levels of DCTN1 mRNA and protein have been found in sporadic amyotrophic lateral sclerosis (ALS) patients, and mutations have been associated with disease, but the role of this protein in disease pathog...

Asynchronous transmission plays a prominent role at certain synapses but lacks the mechanistic insights of its synchronous counterpart. The current view posits that triggering of asynchronous release during repetitive stimulation involves expansion of the same calcium domains underlying synchronous transmission. In this study, live imaging and pair...

Glutamate transporters (excitatory amino acid transporter (EAATs)) are critical for normal excitatory signaling and maintaining subtoxic glutamate concentrations in mammalian central nervous system. Recently, a crystal structure for a homologous transporter in bacteria was reported. Still, little is understood regarding the mechanism of substrate u...

The emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity deriv...