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1.
Neuroscience ; 276: 135-47, 2014 Sep 12.
Article in English | MEDLINE | ID: mdl-24291730

ABSTRACT

Conduction time is typically ignored in computational models of neural network function. Here we consider the effects of conduction delays on the synchrony of neuronal activity and neural oscillators, and evaluate the consequences of allowing conduction velocity (CV) to be regulated adaptively. We propose that CV variation, mediated by myelin, could provide an important mechanism of activity-dependent nervous system plasticity. Even small changes in CV, resulting from small changes in myelin thickness or nodal structure, could have profound effects on neuronal network function in terms of spike-time arrival, oscillation frequency, oscillator coupling, and propagation of brain waves. For example, a conduction delay of 5ms could change interactions of two coupled oscillators at the upper end of the gamma frequency range (∼100Hz) from constructive to destructive interference; delays smaller than 1ms could change the phase by 30°, significantly affecting signal amplitude. Myelin plasticity, as another form of activity-dependent plasticity, is relevant not only to nervous system development but also to complex information processing tasks that involve coupling and synchrony among different brain rhythms. We use coupled oscillator models with time delays to explore the importance of adaptive time delays and adaptive synaptic strengths. The impairment of activity-dependent myelination and the loss of adaptive time delays may contribute to disorders where hyper- and hypo-synchrony of neuronal firing leads to dysfunction (e.g., dyslexia, schizophrenia, epilepsy).


Subject(s)
Brain Waves , Brain/physiology , Myelin Sheath/physiology , Neural Conduction , Neuronal Plasticity , Neurons/physiology , Action Potentials/physiology , Animals , Computer Simulation , Humans , Models, Neurological , Nerve Net/physiology
2.
Novartis Found Symp ; 239: 160-72; discussion 172-6, 234-40, 2001.
Article in English | MEDLINE | ID: mdl-11529310

ABSTRACT

Nervous system development and plasticity are regulated by neural impulse activity, but it is not well understood how the pattern of action potential firing could regulate the expression of genes responsible for long-term adaptive responses in the nervous system. Studies on mouse sensory neurons in cell cultures equipped with stimulating electrodes show that specific genes can be regulated by different patterns of action potentials, and that the temporal dynamics of intracellular signalling cascades are critical in decoding and integrating information contained in the pattern of neural impulse activity. Functional consequences include effects on neurite outgrowth, cell adhesion, synaptic plasticity and axon-glial interactions. Signalling pathways involving Ca2+, CaM KII, MAPK and CREB are particularly important in coupling action potential firing to the transcriptional regulation of both neurons and glia, and in the conversion of short-term to long-term memory. Action potentials activate multiple convergent and divergent pathways, and the complex network properties of intracellular signalling and transcriptional regulatory mechanisms contribute to spike frequency decoding.


Subject(s)
Action Potentials/physiology , Gene Expression Regulation , Nerve Net/physiology , Signal Transduction/physiology , Animals , Calcium Signaling , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Hippocampus/physiology , Mice , Neuroglia/physiology , Phosphorylation , Proto-Oncogene Proteins c-fos/genetics , Transcription, Genetic
3.
Am J Physiol Lung Cell Mol Physiol ; 281(3): L524-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11504675

ABSTRACT

This symposium was organized to present research dealing with the effects of intermittent hypoxia on cardiorespiratory systems and cellular mechanisms. The pattern of neural impulse activity has been shown to be critical in the induction of genes in neuronal cells and involves distinct signaling pathways. Mechanisms associated with different patterns of intermittent hypoxia might share similar mechanisms. Chronic intermittent hypoxia selectively augments carotid body sensitivity to hypoxia and causes long-lasting activation of sensory discharge. Intermittent hypoxia also activates hypoxia-inducible factor-1. Reactive oxygen species are critical in altering carotid body function and hypoxia-inducible factor-1 activation caused by intermittent hypoxia. Blockade of serotonin function in the spinal cord prevents long-term facilitation in respiratory motor output elicited by episodic hypoxia and requires de novo protein synthesis. Chronic intermittent hypoxia leads to sustained elevation in arterial blood pressure and is associated with upregulation of catecholaminergic and renin-angiotensin systems and downregulation of nitric oxide synthases.


Subject(s)
Hypoxia/physiopathology , Animals , Blood Pressure , Calcium/metabolism , Carotid Body/physiopathology , Gene Expression Regulation , Humans , Hypoxia/pathology , Intracellular Membranes/metabolism , Motor Neurons/physiology , Respiratory Muscles/innervation , Respiratory Muscles/physiopathology , Signal Transduction , Transcription Factors/physiology
4.
J Neurosci ; 21(17): 6694-705, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11517259

ABSTRACT

Autonomous activation of calcium-calmodulin kinase (CaMKII) has been proposed as a molecular mechanism for decoding Ca(2+) spike frequencies resulting from action potential firing, but this has not been investigated in intact neurons. This was studied in mouse DRG neurons in culture using confocal measurements of [Ca(2+)](i) and biochemical measurements of CaMKII autophosphorylation and autonomous activity. Using electrical stimulation at different frequencies, we find that CaMKII autonomous activity reached near maximal levels after approximately 45 impulses, regardless of firing frequency (1-10 Hz), and autonomous activity declined with prolonged stimulation. Frequency-dependent activation of CaMKII was limited to spike frequencies in the range of 0.1-1 Hz, despite marked increases in [Ca(2+)](i) at higher frequencies (1-30 Hz). The high levels of autonomous activity measured before stimulation and the relatively long duration of Ca(2+) spikes induced by action potentials ( approximately 300 msec) are consistent with the lower frequency range of action potential decoding by CaMKII. The high autonomous activity under basal conditions was associated with extracellular [Ca(2+)], independently from changes in [Ca(2+)](i), and unrelated to synaptic or spontaneous impulse activity. CaMKII autonomous activity in response to brief bursts of action potentials correlated better with the frequency of Ca(2+) transients than with the concentration of [Ca(2+)](i). In conclusion, CaMKII may decode frequency-modulated responses between 0.1 and 1 Hz in these neurons, but other mechanisms may be required to decode higher frequencies. Alternatively, CaMKII may mediate high-frequency responses in subcellular microdomains in which the enzyme is maintained at a low level of autonomous activity or the Ca(2+) transients have faster kinetics.


Subject(s)
Action Potentials/physiology , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Ganglia, Spinal/metabolism , Neurons/metabolism , Animals , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Calcium-Calmodulin-Dependent Protein Kinases/analysis , Cells, Cultured , Chelating Agents/pharmacology , Diffusion Chambers, Culture , Electric Stimulation/methods , Enzyme Activation/drug effects , Enzyme Activation/physiology , Fluorescent Dyes , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Immunohistochemistry , Intracellular Fluid/metabolism , Mice , Neurons/cytology , Neurons/drug effects , Phosphorylation , Reaction Time/physiology , Tetrodotoxin/pharmacology , Time Factors
5.
J Neurosci ; 21(2): RC122, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11160456

ABSTRACT

Mitogen-activated protein kinase (MAPK) has been identified as a potential element in regulating excitability, long-term potentiation (LTP), and gene expression in hippocampal neurons. The objective of the present study was to determine whether the pattern and intensity of synaptic activity could differentially regulate MAPK phosphorylation via selective activation of different modes of calcium influx into CA1 pyramidal neurons. An antibody specific for the phosphorylated (active) form of MAPK was used to stain sections from hippocampal slices, which were first stimulated in vitro. LTP-inducing stimulation [theta-burst (TBS) and 100 Hz] was effective in inducing intense staining in both dendritic and somatic compartments of CA1 neurons. Phosphorylation of MAPK was also induced, however, with stimulation frequencies (3-10 Hz) not typically effective in inducing LTP. Intensity and extent of staining was better correlated with the spread of population spikes across the CA1 subfield than with frequency (above 3 Hz). Experiments using inhibitors of NMDA receptors and voltage-sensitive calcium channels (VSCCs) revealed that, although MAPK is activated after both TBS and 5 Hz stimulation, the relative contribution of calcium through L-type calcium channels differs. Blockade of NMDA receptors alone was sufficient to prevent MAPK phosphorylation in response to 5 Hz stimulation, whereas inhibitors of both NMDA receptors and VSCCs were necessary for inhibition of the TBS-induced staining. We conclude that the intensity and frequency of synaptic input to CA1 hippocampal neurons are critically involved in determining the path by which second-messenger cascades are activated to activate MAPK.


Subject(s)
Calcium/metabolism , Dendrites/enzymology , Mitogen-Activated Protein Kinases/metabolism , Pyramidal Cells/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Calcium Channel Blockers/pharmacology , Calcium Channels/metabolism , Cell Compartmentation/physiology , Dendrites/drug effects , Electric Stimulation/methods , Excitatory Amino Acid Antagonists/pharmacology , Hippocampus/cytology , Hippocampus/physiology , In Vitro Techniques , Long-Term Potentiation/drug effects , Long-Term Potentiation/physiology , Mice , Phosphorylation , Pyramidal Cells/drug effects , Pyramidal Cells/ultrastructure , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
6.
J Biol Chem ; 276(14): 11021-30, 2001 Apr 06.
Article in English | MEDLINE | ID: mdl-11124944

ABSTRACT

The real time dynamics of vanilloid-induced cytotoxicity and the specific deletion of nociceptive neurons expressing the wild-type vanilloid receptor (VR1) were investigated. VR1 was C-terminally tagged with either the 27-kDa enhanced green fluorescent protein (eGFP) or a 12-amino acid epsilon-epitope. Upon exposure to resiniferatoxin, VR1eGFP- or VR1epsilon-expressing cells exhibited pharmacological responses similar to those of cells expressing the untagged VR1. Within seconds of vanilloid exposure, the intracellular free calcium ([Ca(2+)](i)) was elevated in cells expressing VR1. A functional pool of VR1 also was localized to the endoplasmic reticulum that, in the absence of extracellular calcium, also was capable of releasing calcium upon agonist treatment. Confocal imaging disclosed that resiniferatoxin treatment induced vesiculation of the mitochondria and the endoplasmic reticulum ( approximately 1 min), nuclear membrane disruption (5-10 min), and cell lysis (1-2 h). Nociceptive primary sensory neurons endogenously express VR1, and resiniferatoxin treatment induced a sudden increase in [Ca(2+)](i) and mitochondrial disruption which was cell-selective, as glia and non-VR1-expressing neurons were unaffected. Early hallmarks of cytotoxicity were followed by specific deletion of VR1-expressing cells. These data demonstrate that vanilloids disrupt vital organelles within the cell body and, if administered to sensory ganglia, may be employed to rapidly and selectively delete nociceptive neurons.


Subject(s)
Receptors, Drug/metabolism , Signal Transduction , Animals , Biological Transport , COS Cells , Capsaicin/pharmacology , Green Fluorescent Proteins , Ligands , Luminescent Proteins , Microscopy, Confocal , Receptors, Drug/agonists , TRPV Cation Channels
7.
Curr Protoc Neurosci ; Chapter 2: Unit 2.3, 2001 May.
Article in English | MEDLINE | ID: mdl-18428458

ABSTRACT

Optical imaging methods rely upon visualization of three types of signals: (1) intrinsic optical signals, including light scattering and reflectance, birefringence, and spectroscopic changes of intrinsic molecules, such as NADH or oxyhemoglobin; (2) changes in fluorescence or absorbance of voltage-sensitive membrane dyes; and (3) changes in fluorescence or absorbance of calcium-sensitive indicator dyes. Of these, the most widely used approach is fluorescent microscopy of calcium-sensitive dyes. This unit describes protocols for the use of calcium-sensitive dyes and voltage-dependent dyes for studies of neuronal activity in culture, tissue slices, and en-bloc preparations of the central nervous system.


Subject(s)
Microscopy, Fluorescence/methods , Nervous System/cytology , Nervous System/metabolism , Animals , Cells, Cultured , Fluorescent Dyes/analysis , Humans , Microscopy, Fluorescence/instrumentation , Nervous System/chemistry , Neurons/chemistry , Neurons/cytology , Neurons/metabolism
8.
Science ; 287(5461): 2267-71, 2000 Mar 24.
Article in English | MEDLINE | ID: mdl-10731149

ABSTRACT

Sensory axons become functional late in development when Schwann cells (SC) stop proliferating and differentiate into distinct phenotypes. We report that impulse activity in premyelinated axons can inhibit proliferation and differentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through P2 receptors on SCs and intracellular signaling pathways involving Ca2+, Ca2+/calmodulin kinase, mitogen-activated protein kinase, cyclic adenosine 3',5'-monophosphate response element binding protein, and expression of c-fos and Krox-24. Adenosine triphosphate arrests maturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through this mechanism, functional activity in the developing nervous system could delay terminal differentiation of SCs until exposure to appropriate axon-derived signals.


Subject(s)
Axons/physiology , Immediate-Early Proteins , Neurons, Afferent/physiology , Schwann Cells/cytology , Schwann Cells/physiology , Action Potentials , Adenosine Triphosphate/metabolism , Animals , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cell Differentiation , Cell Division , Cells, Cultured , Coculture Techniques , Cyclic AMP Response Element-Binding Protein/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Early Growth Response Protein 1 , Electric Stimulation , Ganglia, Spinal/physiology , Gene Expression Regulation, Developmental , Genes, fos , Mice , Microscopy, Confocal , Myelin Sheath/metabolism , Phosphorylation , Proto-Oncogene Proteins c-fos/metabolism , Receptors, Purinergic P2/metabolism , Signal Transduction , Transcription Factors/genetics , Transcription Factors/metabolism
9.
Trends Neurosci ; 23(12): 625-33, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11137153

ABSTRACT

Recent studies on Schwann cells at the neuromuscular junction and non-synaptic regions of premyelinated axons indicate that extracellular ATP can act as an activity-dependent signaling molecule in communication between neurons and glia. Several mechanisms have been observed for the regulated release of ATP from synaptic and non-synaptic regions, and a diverse family of receptors for extracellular ATP has been characterized. The findings suggest functional consequences of neuron-glial communication beyond homeostasis of the extracellular environment surrounding neurons, including regulating synaptic strength, gene expression, mitotic rate, and differentiation of glia according to impulse activity in neural circuits.


Subject(s)
Adenosine Triphosphate/metabolism , Neuroglia/metabolism , Neurons/metabolism , Receptors, Purinergic/physiology , Signal Transduction/physiology , Synapses/metabolism , Action Potentials/physiology , Animals , Ganglia, Spinal/metabolism , Humans
10.
Curr Opin Neurobiol ; 9(1): 110-20, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10072371

ABSTRACT

Patterned neural activity modifies central synapses during development and the physiological properties of skeletal muscle by selectively repressing or stimulating transcription of distinct genes. The effects of neural activity are mostly mediated by calcium. Of particular interest are the cellular mechanisms that may be used to sense and convert changes in calcium into specific alterations in gene expression. Recent studies have addressed the importance of spatial heterogeneity or of temporal changes in calcium levels for the regulation of gene expression.


Subject(s)
Action Potentials/genetics , Gene Expression Regulation, Developmental/drug effects , Motor Neurons/physiology , Muscle, Skeletal/embryology , Animals , Calcium/physiology , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Calcium-Calmodulin-Dependent Protein Kinases/physiology , Calmodulin/physiology , Drosophila , Genes, Immediate-Early , Humans , Muscle, Skeletal/innervation
11.
J Neurosci ; 18(22): 9303-11, 1998 Nov 15.
Article in English | MEDLINE | ID: mdl-9801369

ABSTRACT

A cell culture preparation equipped with stimulating electrodes was used to investigate whether action potential activity can influence myelination of mouse dorsal root ganglia axons by Schwann cells. Myelination was reduced to one-third of normal by low-frequency impulse activity (0.1 Hz), but higher-frequency stimulation (1 Hz) had no effect. The number of Schwann cells and the ultrastructure of compact myelin were not affected. The frequency of stimulation that inhibited myelination decreased expression of the cell adhesion molecule L1, and stimulation under conditions that prevented the reduction in L1 blocked the effects on myelination. This link between myelination and functional activity in the axon at specific frequencies that change axonal expression of L1 could have important consequences for the structural and functional relationship of myelinating axons.


Subject(s)
Myelin Sheath/physiology , Neurons/physiology , Schwann Cells/physiology , Action Potentials/physiology , Animals , Cell Adhesion Molecules/physiology , Cells, Cultured , Diffusion Chambers, Culture , Electric Stimulation , Electrophysiology , Ganglia, Spinal/cytology , Gene Expression/physiology , Leukocyte L1 Antigen Complex , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mice , Microscopy, Electron , Myelin Sheath/ultrastructure , Nerve Fibers, Myelinated/chemistry , Nerve Fibers, Myelinated/physiology , Nerve Fibers, Myelinated/ultrastructure , Neural Cell Adhesion Molecules/genetics , Neural Cell Adhesion Molecules/metabolism , Neurons/cytology , Neurons/ultrastructure , RNA, Messenger/analysis , Schwann Cells/cytology
12.
J Neurobiol ; 37(1): 158-70, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9777739

ABSTRACT

Studies of mouse dorsal root ganglion neurons in vitro demonstrate that ion channel function and regulation can influence a wide range of developmental processes. The work suggests that much as exposure to different trophic factors, the pattern of impulse activity a neuron experiences can have significant structural and functional effects during development. Studies concerning effects of ion channel activity on growth cone motility, axon fasciculation, synaptic plasticity, myelination, and intracellular signaling pathways regulating gene expression are presented in the context of changes in endogenous firing patterns during development.


Subject(s)
Calcium Channels/metabolism , Ganglia, Spinal/embryology , Neurons, Afferent/metabolism , Synapses/metabolism , Action Potentials/physiology , Animals , Cell Adhesion Molecules/metabolism , Evoked Potentials/physiology , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Gene Expression Regulation, Developmental , Growth Cones/metabolism , Mice , Neuronal Plasticity
13.
Neuroreport ; 9(7): 1533-6, 1998 May 11.
Article in English | MEDLINE | ID: mdl-9631462

ABSTRACT

Both target-derived and injury-induced factors could be involved in the axotomy-induced increases in galanin expression in dorsal root, ganglion (DRG) neurons. Galanin mRNA levels were studied in primary cultures of E13.5 embryos, grown for 14 days in culture, in response to two candidate molecules, nerve growth factor (NGF) and leukemia inhibitory factor (LIF). In these cultures, NGF withdrawal alone resulted in a significant increase in galanin mRNA. Addition of LIF onto NGF-containing cultures did not produce a significant increase, while addition of LIF to NGF-deprived cultures caused an upregulation of galanin mRNA which was significantly stronger than that of NGF withdrawal alone. Thus, NGF withdrawal and LIF increase act together to up-regulate galanin gene transcription in DRG neurons.


Subject(s)
Galanin/biosynthesis , Ganglia, Spinal/metabolism , Gene Expression Regulation/drug effects , Growth Inhibitors/pharmacology , Interleukin-6 , Lymphokines/pharmacology , Nerve Growth Factors/pharmacology , Neurons/metabolism , Animals , Cells, Cultured , Embryo, Mammalian , Ganglia, Spinal/cytology , Leukemia Inhibitory Factor , Mice , Neurons/cytology , Neurons/drug effects , Polymerase Chain Reaction , RNA, Messenger/biosynthesis , Time Factors , Transcription, Genetic/drug effects
14.
J Neurobiol ; 33(6): 735-48, 1997 Nov 20.
Article in English | MEDLINE | ID: mdl-9369148

ABSTRACT

Cell adhesion molecule (CAM) expression is highly regulated during nervous system development to control cell migration, neurite outgrowth, fasciculation, and synaptogenesis. Using electrical stimulation of mouse dorsal root ganglion (DRG) neurons in cell culture, this work shows that N-cadherin expression is regulated by neuronal firing, and that expression of different CAMs is regulated by distinct patterns of neural impulses. N-cadherin was down-regulated by 0.1 or 1 Hz stimulation, but NCAM mRNA and protein levels were not altered by stimulation. L1 was down-regulated by 0.1 Hz stimulation, but not by 0.3 Hz, 1 Hz, or pulsed stimulation. N-cadherin expression was lowered with faster kinetics than L1 (1 vs. 5 days), and L1 mRNA returned to higher levels after terminating the stimulus. The RSLE splice variant of L1 was not regulated by action potential stimulation, and activity-dependent influences on L1 expression were blocked by target-derived influences. The results are consistent with changes in firing pattern accompanying DRG development and suggest that functional activity can influence distinct developmental processes by regulating the relative abundance of different CAMs.


Subject(s)
Cadherins/biosynthesis , Ganglia, Spinal/metabolism , Gene Expression Regulation, Developmental/physiology , Membrane Glycoproteins/biosynthesis , Neural Cell Adhesion Molecules/biosynthesis , Action Potentials/physiology , Animals , Cadherins/genetics , Cells, Cultured , Electric Stimulation , Electrophoresis, Polyacrylamide Gel , Fetus , Ganglia, Spinal/growth & development , Immunoblotting , Immunohistochemistry , Leukocyte L1 Antigen Complex , Membrane Glycoproteins/genetics , Mice , Neural Cell Adhesion Molecules/genetics , Polymerase Chain Reaction , RNA, Messenger/analysis , RNA-Directed DNA Polymerase
15.
J Neurosci ; 17(19): 7252-66, 1997 Oct 01.
Article in English | MEDLINE | ID: mdl-9295372

ABSTRACT

Specific patterns of neural impulses regulate genes controlling nervous system development and plasticity, but it is not known how intracellular signaling cascades and transcriptional activation mechanisms can regulate specific genes in response to specific patterns of action potentials. Studies using electrical stimulation of mouse dorsal root ganglion neurons in culture show that the temporal dynamics of intracellular signaling pathways are an important factor. Expression of c-fos varied inversely with the interval between repeated bursts of action potentials. Transcription was not dependent on a large or sustained increase in intracellular Ca2+, and high Ca2+ levels separated by long interburst intervals (5 min) produced minimal increases in c-fos expression. Levels of the transcription factor cAMP-responsive element binding protein (CREB), phosphorylated at Ser-133, increased rapidly in response to brief action potential stimulation but remained at high levels several minutes after an action potential burst. These kinetics limited the fidelity with which P-CREB could follow different patterns of action potentials, and P-CREB levels were not well correlated with c-fos expression. The extracellular-regulated kinase (ERK) mitogen-activated protein kinases (MAPK) also were stimulated by action potentials of appropriate temporal patterns. Bursts of action potentials separated by long intervals (5 min) did not activate MAPK effectively, but they did increase CREB phosphorylation. This was a consequence of the more rapid dephosphorylation of MAPK in comparison to CREB. High expression of c-fos was dependent on the combined activation of the MAPK pathway and phosphorylation of CREB. These observations show that temporal features of action potentials (and associated Ca2+ transients) regulate expression of neuronal genes by activating specific intracellular signaling pathways with appropriate temporal dynamics.


Subject(s)
Action Potentials/physiology , Calcium-Calmodulin-Dependent Protein Kinases/physiology , Cyclic AMP Response Element-Binding Protein/physiology , Gene Expression Regulation , Signal Transduction , Animals , Calcium/metabolism , Cells, Cultured , Cyclic AMP Response Element-Binding Protein/metabolism , Electric Stimulation , Electrophysiology , Enzyme Activation/physiology , Ganglia, Spinal/cytology , Mice/embryology , Neurons/physiology , Phosphorylation , Proto-Oncogene Proteins c-fos/metabolism , Time Factors
16.
Clin Orthop Relat Res ; (335): 224-32, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9020222

ABSTRACT

Magnetic resonance imaging has been said to be highly reliable for diagnosis of acute posterior cruciate ligament insufficiency. In the present study, 13 patients whose posterior cruciate ligament insufficiency had been documented by magnetic resonance imaging within 10 weeks of the acute injury were recalled for a followup examination and magnetic resonance imaging. The followup interval ranged from 5 months to 4 years. In only 23% of the cases did the posterior cruciate ligament still appear discontinuous on followup magnetic resonance imaging. In the remaining 77%, the posterior cruciate ligament was continuous from tibia to femur, although it appeared abnormally arcuate or hyperbuckled. Conventional interpretation of these magnetic resonance images would suggest that the posterior cruciate ligament had healed. Nevertheless, by clinical examination results, these same patients all were judged to have posterior cruciate ligament insufficiency. Thus, it was concluded that although magnetic resonance imaging may be reliable for evaluation of acute posterior cruciate ligament injury, magnetic resonance imaging findings should not be used to infer functional status in chronic cases.


Subject(s)
Magnetic Resonance Imaging , Posterior Cruciate Ligament/injuries , Posterior Cruciate Ligament/pathology , Chronic Disease , Humans , Knee Injuries/pathology , Knee Injuries/rehabilitation , Knee Joint/physiology , Range of Motion, Articular , Retrospective Studies
17.
Trends Neurosci ; 19(11): 473-80, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8931273

ABSTRACT

Cell adhesion molecules (CAMs) have a vital role in forming connections between neurons during embryonic development. Increasing evidence suggests that CAMs also participate in activity-dependent plasticity during development and synaptic plasticity in adults. Neural impulses of appropriate patterns can regulate expression of specific CAMs in mouse neurons from dorsal-root ganglia, alter cell-cell adhesion and produce structural reorganization of axon terminals in culture. Synaptic plasticity in Aplysia, learning in chick and long-term potentiation in rat hippocampus are accompanied by changes in CAM expression. Long-term potentiation can be blocked by disrupting CAM function in rat hippocampus, and learning deficits result from antibody blockade of CAMs in chicks and in transgenic mice lacking specific CAMs. Cell adhesion molecules might produce these effects by controlling several cellular processes, including cell adhesion, cytoskeletal structure and intracellular signaling.


Subject(s)
Cell Adhesion Molecules/physiology , Ganglia, Spinal/metabolism , Neuronal Plasticity/physiology , Presynaptic Terminals/physiology , Animals , Mice , Rats
18.
J Neurophysiol ; 76(4): 2595-607, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8899630

ABSTRACT

Electrical activation of mouse dorsal root ganglion (DRG) neurons in cultures for 1-2 days produced a downregulation of voltage sensitive calcium currents, which persisted for > or = 24 h after stimulation was terminated. This regulation varied with different patterns of activation. Both the magnitude and time course of regulation of the low-threshold voltage-activated (LVA) and high-threshold voltage-activated (HVA) currents were differentially sensitive to neural impulse activity. Tonic stimulation at 0.5 Hz did not affect the HVA currents, but 2.5 Hz did produce a significant decrease. Phasic stimulation (10 Hz for 0.5 s every 2 s) with an average frequency of 2.5 Hz produced significantly more downregulation of HVA currents than did the tonic 2.5-Hz stimulation. The efficacy of phasic stimulation varied inversely with the interval between bursts. Thus phasic stimulation of 10 Hz for 0.5 s but delivered every 4 s produced no effects on HVA currents. Stimulation optimal for downregulation of Ca2+ currents also produced a decreased binding by the DRG neurons of an L-type Ca2+ channel antagonist. This suggests a downregulation by electrical activity of the number of Ca2+ channels, rather than an alteration in a constant number of channels. Depression of LVA currents was produced by all stimulus patterns tested, including 0.5-Hz tonic stimulation. Chronic stimulation with a stimulation pattern that downregulated Ca2+ currents also produced a slowing of the increase in intracellular Ca2+ (as measured by Fura-2/AM) that is produced acutely by repetitive stimulation. This is consonant with earlier studies of intracellular Ca2+ concentration kinetics in growth cones.


Subject(s)
Calcium Channels/physiology , Ganglia, Spinal/physiology , Neurons/physiology , Animals , Cells, Cultured , Down-Regulation , Electric Stimulation , Evoked Potentials/physiology , Ganglia, Spinal/cytology , Membrane Potentials/physiology , Mice , Patch-Clamp Techniques , Statistics, Nonparametric
19.
J Hered ; 87(1): 77-80, 1996.
Article in English | MEDLINE | ID: mdl-8742822

ABSTRACT

Homozygous and hybrid clonal lines of rainbow trout (Oncorhynchus mykiss) were confirmed to be isogenic using multilocus DNA fingerprinting. Homozygous clones were produced by androgenesis and gynogenesis using gametes from androgenetic male and female rainbow trout, respectively. Isogenic F1 hybrid lines were produced by crossing homozygous fish from different strains. One line of hybrid clones showed segregation for maternally inherited DNA fingerprint markers. The female from this cross, the only presumptive homozygous gynogenetic individual used in this study, was thought to have been produced by gynogenesis followed by blockage of the first cleavage division, but based on the DNA fingerprint analysis, apparently was derived by spontaneous polar body retention that maintained heterozygosity at some loci. Mutations at DNA fingerprint loci were not observed, indicating relative stability of fingerprint loci in the clonal lines. DNA fingerprinting appears to be a useful tool for identifying and genetically monitoring clonal lines of rainbow trout. Isogenic lines of rainbow trout will facilitate the production of saturated genetic maps for rainbow trout and enhance such endeavors as quantitative trait locus (QTL) analysis and loss of heterozygosity (LOH) studies in tumors.


Subject(s)
Androgens/genetics , DNA Fingerprinting , Oncorhynchus mykiss/genetics , Animals , Base Sequence , Chromosome Mapping , Crosses, Genetic , DNA Probes , Female , Heterozygote , Homozygote , Male , Minisatellite Repeats , Molecular Sequence Data
20.
Science ; 270(5240): 1369-72, 1995 Nov 24.
Article in English | MEDLINE | ID: mdl-7481827

ABSTRACT

Development of the mammalian nervous system is regulated by neural impulse activity, but the molecular mechanisms are not well understood. If cell recognition molecules [for example, L1 and the neural cell adhesion molecule (NCAM)] were influenced by specific patterns of impulse activity, cell-cell interactions controlling nervous system structure could be regulated by nervous system function at critical stages of development. Low-frequency electrical pulses delivered to mouse sensory neurons in culture (0.1 hertz for 5 days) down-regulated expression of L1 messenger RNA and protein (but not NCAM). Fasciculation of neurites, adhesion of neuroblastoma cells, and the number of Schwann cells on neurites was reduced after 0.1-hertz stimulation, but higher frequencies or stimulation after synaptogenesis were without effect.


Subject(s)
Neural Cell Adhesion Molecules/biosynthesis , Neurons, Afferent/metabolism , Animals , Axons/physiology , Cell Adhesion , Cells, Cultured , Down-Regulation , Electric Stimulation , Ganglia, Spinal/cytology , Leukocyte L1 Antigen Complex , Mice , Nerve Growth Factors/pharmacology , Neural Cell Adhesion Molecules/genetics , Neurites/physiology , Neurons, Afferent/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Schwann Cells/physiology , Spinal Cord/cytology , Spinal Cord/physiology , Tumor Cells, Cultured
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