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J N Barrett

Publications and source records attributed to J N Barrett.

51 records · Page 3Linked to original sources
PubMed1980

Characterization of the turning response of dorsal root neurites toward nerve growth factor.

This study reports that chick dorsal root ganglion neurites undergo a rapid (20 min) reorientation of their direction of growth in response to nerve growth factor (NGF) concentration gradients in vitro. Dorsal root ganglia from chick embryos were explanted onto a collagen-poly-L-lysine substrate. After 24-48 h in culture, NGF gradients were applied to individual growth cones via a micropipette containing 50 biological units NGF/ml. The growth cones turned and grew toward these NGF sources. This turning response was not caused by the trophic effects of NGF on neurite initiation, survival, or growth rate. Dorsal root neurites also grew toward sources of mono- and dibutyryl cyclic adenosine monophosphate (dB cAMP), cyclic guanosine monophosphate (cGMP), and elevated calcium in the presence of the calcium ionophore A23187. These results are consistent with the hypothesis that intracellular levels of cAMP and /or cGMP and calcium may play a role in the turning response of dorsal root neurites toward NGF, but do not establish a causal relationship between the mechanisms of action of NGF, cyclic nucleotides and calcium. Total growth cone adherence to the substrate was measured using a timed microjet of perfusion medium. NGF increased the adherence of growth cones to the substrate, but caffeine and dB cAMP which also elicit the positive turning response, decreased growth cone adherence. Calcium, which did not elicit the positive turning response, produced a greater growth cone adherence to the substrate than that observed with NGF. Although these results do not rule out a role of adhesion changes in axonal turning to NGF, they show that a general increase in adherence does not correlate well with the rapid turning response observed in this study.

Animals↗
PubMed1980

Voltage clamp of cat motoneurone somata: properties of the fast inward current.

1. The soma membrane of cat spinal motoneurones was voltage clamped using separate intracellular voltage and current electrodes directed into the same motoneurone with a new guide system. 2. Antidromic stimulation of the motoneurone's axon or small depolarizing voltage clamp steps (10-20 mV from the resting potential) evoked a small (30-80 nA) all-or-none action potential current, which was shown by occlusion experiments to originate from the initial segment of the axon. Except for this axonal current spike, there was no indication of active (voltage-dependent) conductance changes in membrane regions not under good voltage clamp control. Calculations based on motoneuronal geometry, and electrophysiological recordings from spinal cord neurones in tissue culture, indicate that the proximal portions of dendritic membranes were also under good voltage clamp control. 3. Clamp depolarizations greater than 20 mV activated a fast, transient inward current, which increased in a smoothly graded manner with depolarization between 20 and 40 mV from the resting potential, reaching a peak magnitude of up to 450 nA, and then decreased smoothly for larger depolarizations. Extrapolation of the current-voltage relationship for this current indicated a reversal potential about 80-116 mV positive to the resting potential. 4. This transient inward current is blocked by tetrodotoxin. After a depolarizing voltage clamp step the conductance system controlling this current first activates with fast, non-linear kinetics, and then inactivates with first-order kinetics. These properties are similar to those of the Na conductance system in squid and frog axons. 5. Conditioning-testing experiments showed that the time constant of inactivation ranges from 1.0-1.3 msec at potentials slightly negative to the resting potential to 0.1-0.3 msec for depolarizations 60 mV from the resting potential. The degree of steady-state inactivation also varied with membrane potential, ranging from total inactivation at depolarizations greater than 30 mV from the resting potential, to minimal inactivation at potentials more than 10 mV negative to the resting potential.

Action Potentials↗
PubMed1980

Voltage-sensitive outward currents in cat motoneurones.

1. The soma membrane of cat motoneurones was voltage-clamped in vivo using intracellular current and voltage electrodes whose tips were separated by at least 5 micrometer. 2. Depolarization activates two separate, non-interacting K conductance systems whose rates of activation and decay differ by a factor of about 10. These conductances have a similar reversal potential, in the range of -6 to -21 mV (these and all subsequent voltages are expressed relative to the resting potential). Both conductances show linear 'instantaneous' current-voltage relationships. The steady-state magnitudes of both conductances increase with increasing depolarization. Neither conductance inactivates substantially during prolonged depolarizations. 3. The faster K conductance is similar to that described for squid axons and frog node. Activation begins at about +30 mV and is more than 90% complete within 5 msec of a depolarizing voltage step to +50 mV. Activation kinetics appear to be nonlinear. This fast K conductance contributes to the fast falling phase of the action potential. Following repolarization, this conductance decays with a time constant of 2-4 msec. 4. The slower K conductance activates during depolarizations of 10 mV or greater. The activation and decay of this conductance can be described by first-order exponential functions with time constants ranging from 20 to 50 msec. The slow K conductance underlies the prolonged hyperpolarization that follows motoneurone action potentials. Evidence from other studies suggests that this slow K conductance is regulated by intracellular Ca ions. 5. In addition to the two K conductance systems activated by depolarization, motoneurones exhibit another distinct conductance system that is activated by hyperpolarization. This third system has a reversal potential near the resting potential. Activation of this conductance during a hyperpolarizing voltage step can be fitted by a single exponential function with a time constant of 50-60 msec over the range -20 to -50 mV. This hyperpolarization-activated conductance accounts for some aspects of the anomalous rectification reported in cat motoneurones. 6. When the clamp circuit was turned off and the motoneurones were stimulated to discharge repetitively by depolarizing current steps, the apparent soma threshold voltage increased as the applied current (and discharge frequency) increased. 7. The basic features of the motoneurone action potential were reconstructed by simulations based on voltage clamp measurements of the voltage dependent conductance systems and previous measurements of passive membrane properties. These simulations assumed that the kinetics of the fast Na and K conductance systems in motoneurones can be described by equations of the same form as the Hodgkin-Huxley equations. These action potential reconstructions indicated that a major portion of the delayed depolarization following the action potential is attributable to capacitative currents from the dendrites...

Action Potentials↗
PubMed1978

Temperature-sensitive aspects of evoked and spontaneous transmitter release at the frog neuromuscular junction.

1. The temperature dependence of presynaptic processes involved in neuromuscular transmission was studied by rapidly increasing the temperature of cooled frog neuromuscular junctions by 4--10 degrees C using pulses from a neodymium laser. The temperature elevation was complete within 0.5 msec, and decayed back to control levels with a time constant of about 7--8 sec. 2. Temperature jumps completed before nerve stimulation increased the quantal content and decreased the latency of the end-plate potential (e.p.p.). The Q10 for e.p.p. quantal content in low [Ca2+] Ringer averaged about 3.9 over the range 1--18 degrees C. 3. Temperature jumps occurring during the synaptic delay (the interval between the presynaptic action potential and the onset of the e.p.p.) also increased the quantal content and decreased the latency of the e.p.p. These effects diminished as the onset of the temperature jump was moved closer to the expected onset of the e.p.p. Temperature jumps applied after the onset of the e.p.p. immediately accelerated the time course of the e.p.p. but did not significantly alter quantal content. These results demonstrate that the magnitude and timing of evoked release are influenced by temperature-sensitive processes that operate both during and shortly after the presynaptic nerve action potential, but are largely complete before the onset of release. 4. Temperature jumps were applied at various times during the interval between two nerve stimuli. The amplitude of the second e.p.p. decreased as the temperature jump was moved earlier in the interstimulus interval, suggesting that the rise in temperature following the first nerve stimulus accelerates the decay of facilitation. When the temperature jump was moved from 10 msec after to 10 msec before the onset of the first e.p.p., the amplitude of the second e.p.p. either decreased or showed no change. The fact that the second e.p.p. did not increase suggests that the temperature-sensitive processes that increase the quantal content of the conditioning e.p.p. do not greatly increase the facilitation following that e.p.p. 5. Temperature jumps immediately accelerated the time course of spontaneous miniature end-plate potentials (m.e.p.p.s) and increased their frequency. Experiments using slow temperature changes revealed that the Q10 for m.e.p.p. frequency in normal Ringer is about 10 over the range 10--20 degrees C. M.e.p.p. frequency was much less sensitive to temperature changes below about 10 degrees C. When the nerve terminal was depolarized by 20 mM-K+ in the presence of Ca2+, the Q10 for the rate of spontaneous release over the range 10--20 degrees C decreased to about 4, similar to the Q10 for e.p.p. quantal content. In the absence of extracellular Ca2+ the Q10 for m.e.p.p. frequency in 20 mM-K+ remained near 10. 6. The marked difference in Q10S for spontaneous transmitter release under different experimental conditions suggests that not all transmitter release uses identical mechanisms...

Action Potentials↗
PubMed1975

Epiphysitis in beef cattle fattened on slatted floors.

A syndrome which causes severe lameness and affects the fetlock area of the hind limbs was recently encountered in beef cattle housed on slatted floors. This condition does not appear to have been reported to others. On radiological and pathological examination of the limb, a lesion of epiphysitis was found in the distal epiphysis of the metatarsus. The clinical, radiological and pathological features are reported and discussed.

Animals↗
PubMed1975

Motoneuron dendrites: role in synaptic integration.

Dendrites constitute over 80 per cent of the receptive surface area in cat motoneurons. Calculations based on matched electrical and gemoetrical measurements in these neurons indicate that the specific resistance of dendritic membranes in resting motoneurons is at least 2,000 ohm-cm2. When the specific membrane resistance is this high, even the most distal dendritic synapses can contribute significantly to the depolarization of the soma, and hence influence the rate of action potential generation. However, dendritic membrane resistance depends strongly on the level of background synaptic activity. The conductance changes associated with excitatory synaptic activity on a dendrite can be great enough to reduce significantly both the excitatory synaptic driving potential and the effective membrane resistance on that dendrite, and thus greatly reduce the effectiveness of synapses on the dendrite. Inhibitory synaptic activity produces an even greater reduction in dendritic membrane resistance. Thus the relative effectiveness of dendritic synapses depends on the type, distribution, and intensity of background synaptic activity, as well as on dendritic geometry and resting membrane properties.

Action Potentials↗
PubMed1974

A note on the interaction of spontaneous and evoked release at the frog neuromuscular junction.

1. The interaction between spontaneous miniature end-plate potentials and evoked end-plate potentials was investigated at the frog neuromuscular junction using focal extracellular recording techniques.2. End-plate potentials evoked immediately after a spontaneous miniature potential were facilitated by up to 20%. The percentage facilitation was negatively correlated with the average quantal content of the end-plate potential.

Animals↗
PubMed1974

Specific membrane properties of cat motoneurones.

1. Electrophysiological properties of cat motoneurones were measured using intracellular electrodes, after which Procion dye was injected iontophoretically into the neurone through the recording pipette.2. Histological procedures were chosen to minimize changes in neuronal morphology. Reconstructed motoneurones had more dendritic branches and larger surface areas than the Golgi-stained motoneurones of earlier reports.3. The sum of the 3/2 power of the dendritic diameters (the dendritic trunk parameter; Rall, 1959) of the reconstructed motoneurones was found to decrease with distance from the soma. Thus, the dendritic tree is not satisfactorily approximated by a non-tapering membrane cylinder.4. A computational technique was developed to allow calculation of the specific resistance (R(m)) of the membrane using the measured value of the input resistance of the motoneurone and a more detailed approximation of the dendritic tree. These calculations indicate that the average resting value of dendritic R(m) is at least 1800 Omega cm(2). The specific membrane capacity, calculated assuming uniform R(m), ranged between 2-3 muF/cm(2).

Animals↗
PubMed1974

Influence of dendritic location and membrane properties on the effectiveness of synapses on cat motoneurones.

1. Measurements of the specific membrane properties and neuronal geometry of cat motoneurones were used to calculate the excitatory postsynaptic potentials (e.p.s.p.s) produced by unit (quantal) conductance changes occurring at various locations on the dendritic tree.2. Calculations demonstrate that conductance changes of 80-190 x 10(-10) mho are required to produce e.p.s.p.s having the same rise time and peak amplitude as the quantal e.p.s.p.s recorded in motoneurones by Kuno & Miyahara (1969b). Because quantal conductance changes are so large, synaptic activity can significantly reduce the effective specific resistance of the motoneuronal membrane.3. A quantal conductance change occurring at a high-impedance distal dendritic site is calculated to produce an e.p.s.p. of 15-20 mV peak amplitude at that site. Significant non-linear summation will occur between the e.p.s.p.s produced by conductance changes occurring simultaneously on the same dendritic branch.4. Calculations which take into account both non-linear summation and the loss of synaptic charge through dendritic membranes predict that for these motoneurones the time integral of soma-recorded quantal e.p.s.p.s originating on distal dendrites should be at least 20% as great as the time integral of a quantal e.p.s.p. originating directly on the soma. Quantal conductance changes occurring on 76% of the dendritic tree should produce soma e.p.s.p. time integrals at least 50% as great as those produced by somatic synapses.

Animals↗
PubMedDate not supplied

Neurones express high levels of a structurally modified, activated form of pp60c-src.

Neural tissues contain high levels of the cellular homologue of the transforming protein of Rous sarcoma virus (RSV), but neither the specific cell types expressing high levels of c-src, nor the function of the cellular src (c-src) protein has been determined. Using primary culture methods, we have found that pure neurones and astrocytes derived from the rat central nervous system (CNS) contain 15- to 20-times higher levels of the c-src protein than fibroblasts. However, the specific activity of the c-src protein from the neuronal cultures is 6- to 12-times higher than that from the astrocyte cultures. In addition, the c-src protein expressed in neuronal cultures contains a structural alteration within the amino-terminal region of the molecule that causes a shift in the mobility of the c-src protein on the SDS-polyacrylamide gels. These results indicate that a structurally distinct form of the cellular src protein that possesses an activated tyrosylkinase activity is expressed at very high levels in post-mitotic CNS neurones.

Animals↗