scholarly journals Differential Effects of NGF and BDNF on Axotomy-Induced Changes in GABAA-Receptor-Mediated Conductance and Sodium Currents in Cutaneous Afferent Neurons

1997 ◽  
Vol 78 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Adetokunbo A. Oyelese ◽  
Marco A. Rizzo ◽  
Stephen G. Waxman ◽  
Jeffery D. Kocsis
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Action Potentials ◽  
Afferent Neurons ◽  
Sodium Currents ◽  
Drg Neurons ◽  
Differential Effects ◽  
Action Potential Waveform ◽  
Induced Changes ◽  
Potential Waveform

Oyelese, Adetokunbo A., Marco A. Rizzo, Stephen G. Waxman, and Jeffery D. Kocsis. Differential effects of NGF and BDNF on axotomy-induced changes in GABAA-receptor-mediated conductance and sodium currents in cutaneous afferent neurons. J. Neurophysiol. 78: 31–42, 1997. The effects of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) on injury-induced changes in the electrophysiological properties of adult rat cutaneous afferent dorsal root ganglion (DRG) neurons were examined. Whole cell patch-clamp techniques were used to study γ-aminobutyric acid-A (GABAA)-receptor-mediated conductance, voltage-dependent sodium currents, and action potential waveform in cutaneous afferent neurons (35–60 μm diam) cultured from control and axotomized animals. Cutaneous afferent neuronswere identified by retrograde labeling with hydroxy-stilbamidine (Fluoro-gold, a fluorescent retrograde axonal tracer); the sciatic nerve was transected 1 wk after Fluoro-gold injection and L4/L5 DRG neurons were cultured 2–3 wk after axotomy. NGF, BDNF, or Ringer (vehicle) solution was delivered in vivo directly to the transected sciatic nerve stump in axotomized rats via an osmotic pump. Recordings were obtained from neurons 5–24 h after culture. Axotomized neurons from rats treated with vehicle solution displayed a twofold increase in GABA-induced conductance and a prominent reduction in the proportion of neurons expressing action potentials that had inflections on the falling phase. The expression of kinetically slow tetrodotoxin (TTX)-resistant sodium current was markedly reduced and an increased expression of kinetically fast TTX-sensitive current was observed in neurons from vehicle-treated, axotomized rats. Treatment with NGF (0.25 μg/μl at 12 μl/day for 14 days) in axotomized animals resulted in an increase in the proportion of neurons expressing TTX-resistant, slow sodium currents and inflected action potentials, but had no effect on GABA-induced conductance. Treatment with BDNF (0.5 μg/μl at 12 μl/day for 14 days) attenuated the axotomy-induced increase in GABAA-receptor-mediated conductance while minimally affecting action potential waveform. The observed neurotrophin effects occurred independently of cell size changes. These findings indicate a differential regulation of GABAA receptor and sodium channel properties in axotomized rat cutaneous afferent neurons by specific neurotrophic factors.

scholarly journals GABAA-receptor-mediated conductance and action potential waveform in cutaneous and muscle afferent neurons of the adult rat: differential expression and response to nerve injury

1996 ◽  
Vol 76 (4) ◽  
pp. 2383-2392 ◽  
Author(s):  
A. A. Oyelese ◽  
J. D. Kocsis
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Gabaa Receptor ◽  
Crush Injury ◽  
Resting Potential ◽  
Gamma Aminobutyric Acid ◽  
Afferent Neurons ◽  
Muscle Afferent ◽  
Action Potential Waveform ◽  
Potential Waveform

1. Whole cell patch-clamp recordings were obtained from identified cutaneous and muscle afferent neurons (33-60 microns diam) in dissociated L4 and L5 dorsal root ganglia (DRGs) from normal rats and from rats 2-3 wk after sciatic nerve ligation or crush injury. gamma-Aminobutyric acid (GABA)-induced conductance was compared in normal and injured neurons from both functional classes of sensory neurons. 2. Control cutaneous afferent neurons had a peak GABA-mediated conductance of 287 +/- 27 (SE) nS compared with 457 +/- 42 nS for control muscle afferent neurons. 3. An inflection on the downslope of the action potential was observed in 47% of cutaneous afferent neurons compared with 20% of muscle afferent neurons. 4. After ligation and transection of the sciatic nerve there was no change in the GABA-mediated conductance of muscle afferent neurons or in the action potential waveform (23% inflected). However, the cutaneous afferent neurons displayed a greater than two-fold increase in their GABA-mediated conductance and displayed a prominent reduction in the number of neurons with inflected action potentials (13% inflected). Input resistance was similar in cutaneous and muscle afferent neurons and decreased after ligation in cutaneous but not muscle afferents. Resting potential averaged from -50 to -56 mV in normal and ligated groups for both cutaneous and muscle afferent neurons. 5. After crush injury in cutaneous afferent neurons where the transected axons were allowed to regenerate into the distal nerve stump, GABAA-receptor-mediated conductance was elevated compared with controls. However, action potential waveform was not altered by crush injury, suggesting a differential regulation of these two properties in cutaneous afferent neurons. 6. These data indicate that injury-induced plasticity of GABAA-receptor-mediated conductance and action potential waveform occurs in cutaneous but not muscle afferent DRG neurons. It appears that peripherally derived influences are critical in maintaining the electrophysiological phenotype of cutaneous afferent neurons but not muscle afferent neurons.

scholarly journals Schwann Cell Engraftment Into Injured Peripheral Nerve Prevents Changes in Action Potential Properties

2005 ◽  
Vol 94 (2) ◽  
pp. 1519-1527 ◽  
Author(s):  
Kewei Yu ◽  
Jeffery D. Kocsis
Keyword(s):  
Action Potential ◽  
Peripheral Nerve ◽  
Fluorescent Protein ◽  
Afferent Neurons ◽  
Nerve Crush ◽  
Primary Afferent Neurons ◽  
Primary Afferent ◽  
Action Potential Waveform ◽  
Potential Waveform ◽  
Neuroma Formation

Peripheral nerve injury results in changes in action potential waveform, ion channel organization, and firing properties of primary afferent neurons. It has been suggested that these changes are the result of reduction in basal trophic support from skin targets. Subcutaneous injections of Fluro-Gold (FG) in the hind limb of the rat were used to identify cutaneous primary afferent neurons. Five days after FG injection, sciatic nerves were ligated and encapsulated in a silicon tube allowing neuroma formation. Green fluorescent protein (GFP)-expressing Schwann cells (SCs) were injected proximal to the cut end of the nerve. Thirteen to 22 days after injury and SC injection, the L4 and L5 dorsal root ganglia (DRG) were prepared for acute culture. Whole cell patch-clamp recordings in current clamp mode were obtained and action potential properties of medium-sized (34–45 μm) FG+ DRG neurons were characterized. In the neuroma group without cell transplantation, action potential duration and spike inflections were reduced as were the amplitude and duration of spike afterhyperpolarizations. These changes were not observed after transection by nerve crush where axons were allowed to regenerate to distal peripheral targets. In the transplantation group, GFP+-SCs were extensively distributed throughout the neuroma, and oriented longitudinally along axons proximal to the neuroma. Changes in action potential properties were attenuated in the GFP+-SC group. Thus the engrafted SC procedure ameliorated the changes in action potential waveform of cutaneous primary afferents associated with target disconnection and neuroma formation.

scholarly journals Action Potential Waveform Variability Limits Multi-Unit Separation in Freely Behaving Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38482 ◽  
Author(s):  
Peter Stratton ◽  
Allen Cheung ◽  
Janet Wiles ◽  
Eugene Kiyatkin ◽  
Pankaj Sah ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Waveform ◽  
Freely Behaving ◽  
Potential Waveform

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

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Michael A Gaviño ◽  
Kevin J Ford ◽  
Santiago Archila ◽  
Graeme W Davis
Keyword(s):  
Synaptic Plasticity ◽  
Neuromuscular Junction ◽  
Action Potential ◽  
Calcium Channel ◽  
Neurotransmitter Release ◽  
Calcium Influx ◽  
Homeostatic Synaptic Plasticity ◽  
Action Potential Waveform ◽  
Presynaptic Calcium ◽  
Potential Waveform

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. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

scholarly journals Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1

2022 ◽  
pp. 105609
Author(s):  
Rémi Bos ◽  
Khalil Rihan ◽  
Patrice Quintana ◽  
Lara El-Bazzal ◽  
Nathalie Bernard-Marissal ◽  
...  
Keyword(s):  
Action Potential ◽  
Motor Neurons ◽  
Initial Segment ◽  
Axonal Initial Segment ◽  
Action Potential Waveform ◽  
Potential Waveform

Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons

2001 ◽  
Vol 86 (2) ◽  
pp. 629-640 ◽  
Author(s):  
Muthukrishnan Renganathan ◽  
Theodore R. Cummins ◽  
Stephen G. Waxman
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Action Potentials ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Drg Neurons ◽  
Significant Difference ◽  
Steady State Inactivation ◽  
Current Threshold

C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Nav1.8 (+/+) and (−/−) small DRG neurons maintained for 2–8 h in vitro to examine the role of sodium channel Nav1.8 (α-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Nav1.8 (+/+) and (−/−) DRG neurons, there were significant differences in action potential electrogenesis. Most Nav1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Nav1.8 (−/−) neurons produce smaller graded responses. The peak of the response was significantly reduced in Nav1.8 (−/−) neurons [31.5 ± 2.2 (SE) mV] compared with Nav1.8 (+/+) neurons (55.0 ± 4.3 mV). The maximum rise slope was 84.7 ± 11.2 mV/ms in Nav1.8 (+/+) neurons, significantly faster than in Nav1.8 (−/−) neurons where it was 47.2 ± 1.3 mV/ms. Calculations based on the action potential overshoot in Nav1.8 (+/+) and (−/−) neurons, following blockade of Ca2+ currents, indicate that Nav1.8 contributes a substantial fraction (80–90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na+ channels can produce all-or-none action potentials in some Nav1.8 (−/−) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Nav1.8 (−/−) neurons is more sensitive to membrane depolarization than in Nav1.8 (+/+) neurons, and, in the absence of Nav1.8, is attenuated with even modest depolarization. These observations indicate that Nav1.8 contributes substantially to action potential electrogenesis in C-type DRG neurons.

scholarly journals Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum

2020 ◽  
Vol 10 (12) ◽  
pp. 897
Author(s):  
Tara Barron ◽  
Jun Hee Kim
Keyword(s):  
Preterm Birth ◽  
Action Potential ◽  
Purkinje Cell ◽  
Purkinje Cells ◽  
Late Gestation ◽  
Cerebellar Development ◽  
Layer Width ◽  
Action Potential Waveform ◽  
Developmental Features ◽  
Potential Waveform

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.

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