A5000096787- Nerve injury and regeneration
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Gastrointestinal motility and disorders
- Neuroscience and Neural Engineering
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- Congenital gastrointestinal and neural anomalies
- Neuroscience and Neuropharmacology Research
- Zebrafish Biomedical Research Applications
- Neurobiology and Insect Physiology Research
- Neuroendocrine regulation and behavior
- Axon Guidance and Neuronal Signaling
- Photoreceptor and optogenetics research
- Ion Channels and Receptors
- Developmental Biology and Gene Regulation
- Planarian Biology and Electrostimulation
- Amyotrophic Lateral Sclerosis Research
- Infant Health and Development
- Pelvic floor disorders treatments
- Genetic Neurodegenerative Diseases
- Circadian rhythm and melatonin
- Pluripotent Stem Cells Research
- Diet and metabolism studies
- Hereditary Neurological Disorders
University of Nevada, Reno
2016-2025
Indiana University School of Medicine
2020
Salk Institute for Biological Studies
2010-2019
Wake Forest University
1999-2010
National University of Samoa
2008
The death of cranial and spinal motoneurons (MNs) is believed to be an essential component the pathogenesis amyotrophic lateral sclerosis (ALS). We tested this hypothesis by crossing Bax-deficient mice with expressing mutant superoxide dismutase 1 (SOD1), a transgenic model familial ALS. Although Bax deletion failed prevent neuromuscular denervation mitochondrial vacuolization, MNs were completely rescued from SOD1-mediated death. However, deficiency extended lifespan delayed onset motor...
The dependence of developing spinal motoneuron survival on a soluble factor(s) from their target, muscle tissue is well established both in vivo and vitro. Considering this apparent dependence, we examined whether specific component the stress response mediates trophic factor-deprived environments. We demonstrate that, although endogenous expression heat shock protein 70 (HSP70) did not change during factor deprivation, application e-rhHsp70 (exogenous recombinant human Hsp70) promoted...
The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of is believed to be important during development. Here we generated VAChT knockout mice and tested physiological relevance ACh. Homozygous died shortly after birth, indicating that VAChT-mediated essential for life. Indeed, synaptosomes obtained from brains homozygous knockouts were incapable releasing in response depolarization. Surprisingly,...
Significance The peristaltic reflex elicits colonic migrating motor complexes (CMMCs) that are thought to be generated by enteric excitatory neurons stimulating smooth muscle cells (SMCs). We found atropine did not block CMMCs and present a concept showing poststimulus responses following nitrergic in interstitial of Cajal (ICC) responsible for initiation CMMCs. Ca 2+ transients ICC inhibited stimulation. After the inhibitory period, increased, activating currents conducted SMCs initiate...
Using cell-specific tools to image myenteric neurons of mouse colon, we find that distinct subtypes are active during spontaneous neurogenic contractions.The same were evoked contractions, suggesting the existence a common contractile neuronal substrate.
Glial cell line-derived neurotrophic factor (GDNF) regulates multiple aspects of spinal motoneuron (MN) development, including gene expression, target selection, survival, and synapse elimination, mice lacking either GDNF or its receptors family receptor α1 (GFRα1) Ret exhibit a 25% reduction lumbar MNs at postnatal day 0 (P0). Whether this loss reflects generic trophic role for thus all MN subpopulations, more restricted affecting only specific such as those innervating individual muscles,...
Genetically encoded Ca(2+) indicators (GECIs) have been used extensively in many body systems to detect transients associated with neuronal activity. Their adoption enteric neurobiology has slower, although they offer advantages terms of selectivity, signal-to-noise and non-invasiveness. Our aims were utilize a number cell-specific promoters express the indicator GCaMP3 different classes neurons glia determine their effectiveness measuring activity neural networks during colonic motor...
The removal of excess neurons by programmed cell death (PCD) is believed to be critical for the proper development and function nervous system. A major role this neuronal loss attain quantitative matching with their targets afferents. Because motoneurons (MNs) in Bax knock-out (Bax KO) mice fail undergo PCD face normal target muscle development, we asked whether rescued KO can develop normally. We observed many small atrophied MNs postnatal mice, these failed innervate limb targets. When...
The widespread, massive loss of developing neurons in the central and peripheral nervous system birds mammals is generally considered to be an evolutionary adaptation. However, until recently, models for testing both immediate long-term consequences preventing this normal cell have not been available. We taken advantage several methods neuronal death vivo ask whether rescued [e.g., motoneurons (MNs)] differentiate normally become functionally incorporated into system. Although many aspects...
Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates development of neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar blocking biosynthesis, eliminating postsynaptic increased motor axon branching and expanded innervation territory, suggesting synaptic growth AChRs. However, in contrast agrin-deficient mice...
The enteric nervous system in the large intestine generates two important patterns relating to motility: 1) propagating rhythmic peristaltic smooth muscle contractions referred as colonic migrating motor complexes (CMMCs) and 2) tonic inhibition, during which are suppressed. precise neurobiological substrates underlying each of these unclear. Using transgenic animals expressing genetically encoded calcium indicator GCaMP3 monitor activity or optogenetic actuator channelrhodopsin (ChR2) drive...
Perisynaptic glial cells respond to neural activity by increasing cytosolic calcium, but the significance of this pathway is unclear. Terminal/perisynaptic Schwann (TPSCs) are a perisynaptic cell at neuromuscular junction that nerve-derived substances such as acetylcholine and purines. Here, we provide genetic evidence activity-induced calcium accumulation in neonatal TPSCs mediated exclusively one subtype metabotropic purinergic receptor. In P2ry1 mutant mice lacking these responses,...
Mutations in peripheral myelin protein 22 (PMP22) result the most common form of Charcot-Marie-Tooth (CMT) disease, CMT1A. This hereditary neuropathy is characterized by dysmyelination nerves, reduced nerve conduction velocity, and muscle weakness. APMP22 point mutation L16P (leucine 16 to proline) underlies a human CMT1A as well Trembler-J mouse model Homozygote mice (Tr(J)) die early postnatally, fail make myelin, and, therefore, are more similar patients with congenital hypomyelinating...
The internal anal sphincter (IAS) functions to maintain continence. Previous studies utilizing mice with cell-specific expression of GCaMP6f revealed two distinct subtypes intramuscular interstitial cells Cajal (ICC-IM) differing Ca
Growing evidence suggests important roles for specialized platelet-derived growth factor receptor alpha-positive (PDGFRalpha(+)) cells in regulating the behaviors of visceral smooth muscle organs. Examination female reproductive tracts mice and monkeys showed that PDGFRalpha(+) form extensive networks ovary, oviduct, uterus. were located discrete locations within these organs, their distribution density similar rodents primates. distinct from interstitial Cajal (ICC). This was demonstrated...
Glial cells regulate multiple aspects of synaptogenesis. In the absence Schwann cells, a peripheral glial cell, motor neurons initially innervate muscle but then degenerate. Here, using genetic approach, we show that neural activity-regulated negative factors produced by drive neurodegeneration in cell-deficient mice. We find thrombin, hepatic serine protease central to hemostatic coagulation cascade, is one such factor. Trancriptomic analysis shows expression antithrombins serpin C1 and D1...
We examined the spatio-temporal relationship between neurotrophic factor receptor (NTF-R) expression and motoneuron (MN) survival in developing avian spinal cord observed heterogeneity of NTF-Rs between, but not within, pools MNs projecting to individual muscles. then focused on role NTFs regulating one motor pool MNs, all which innervate a pair adductor muscles thigh hence compete for during period programmed cell death (PCD). The complete NTF-R complement these was analyzed found include...
The failure to transmit neural action potentials (APs) into muscle APs is referred as neuromuscular transmission (NTF). Although synaptic dysfunction occurs in a variety of diseases and impaired neurotransmission contributes fatigue, direct evaluation by measurement successfully transduced difficult due the subsequent movements produced muscle. Moreover, voltage-gated sodium channel inhibitor used study neurotransmitter release at adult junction ineffective embryonic tissue, making it nearly...