Robert Zucker | University of California, Berkeley (original) (raw)

Papers by Robert Zucker

The Journal of Physiology, 1974

1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in ... more 1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres.2. Apparent changes in n.t.p. are attributed to three causes.(i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation.(ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies.(iii) Some changes in n.t.p. are blocked by gamma-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements.3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval.4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected.5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses.6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that of e.j.p.s evoked by nerve impulses.7. It is concluded that facilitation in the crayfish claw opener is not due to a change in the presynaptic action potential, but is due to some change at a later step in the depolarization-secretion process.

The Journal of Physiology, 1974

1. A quantitative description of facilitation in the crayfish claw opener muscle is presented. Th... more 1. A quantitative description of facilitation in the crayfish claw opener muscle is presented. The facilitation of a test response following one or more conditioning stimuli, and the growth of facilitation during a tetanus, are measured.2. In superficial central fibres facilitation following one or more impulses can be described as the sum of two components which are both maximum at the end of the conditioning train and decline simultaneously and exponentially with different time constants thereafter.3. During a tetanus, facilitation to successive stimuli grows more rapidly than is predicted by assuming that each impulse adds a constant facilitative effect to an accumulating total state of facilitation.4. Sufficiently large values of tetanic facilitation are predicted by a model which assumes that transmitter release is proportional to the nth power of a substance or factor accumulating in nerve terminals. But no single value of n predicts the correct rise of facilitation in a tetanus and the time course of its subsequent decline from the facilitation following a single spike.5. A model which assumes that the facilitative effects of successive spikes multiply in a tetanus predicts responses that are larger than those observed.6. The effects of varying the calcium concentration ([Ca(2+)]) on transmitter release and facilitation were studied. When a magnesium-EDTA buffering system is used to vary [Ca(2+)], transmitter release is found to be nearly linearly related to [Ca(2+)] in the range 0.1-13.5 mM.7. The magnitude and time course of facilitation during and following a tetanus are unaffected by varying [Ca(2+)] between 1.0 and 40 mM.8. The relation between ;steady-state' facilitation and stimulus frequency is also unaffected by changing [Ca(2+)], except that in high [Ca(2+)] transmitter release appears to saturate at high frequencies (above 30 Hz).9. The results are discussed in terms of the ;calcium accumulation' hypothesis of facilitation. The findings in crayfish appear to be qualitatively consistent with this hypothesis if certain modifications are made in the hypothesis.

The Journal of Physiology, 1980

1. When molluscan neural somata are filled with the calcium-indicating photo-protein aequorin and... more 1. When molluscan neural somata are filled with the calcium-indicating photo-protein aequorin and subjected to a 1 Hz train of depolarizing pulses (0.3 sec duration to + 15 mV) under voltage clamp, the successive photo-emissions due to calcium influx facilitate. The origin of this phenomenon was investigated in identified neurones from the abdominal ganglion of Aplysia californica.2. Since outward currents inactivate cumulatively in successive pulses, the effective depolarization increases due to a series resistance error. Elimination of this error by electronic compensation or pharmacological block of outward current reduced aequorin response facilitation by only about 30%, on the average.3. When voltage-dependent sodium and potassium currents are blocked in tetraethylammonium (TEA)-substituted zero-sodium sea water, the remaining inward calcium currents display no facilitation. On the contrary, a slow decline during a pulse and a slight progressive depression in successive pulses are observed. Barium-substitution for calcium in the same medium eliminates a small residual potassium current insensitive to external TEA. The remaining inward barium currents also display depression instead of facilitation.4. A non-pharmacological separation of calcium current was accomplished by measuring tail currents at the potassium equilibrium potential following depolarizing pulses. Calcium tail currents activate rapidly and then decline gradually and incompletely as depolarizing pulse duration is lengthened. Tail currents also show no evidence of facilitation; there is instead a slight depression of currents after successive pulses.5. Increments of optical absorbance in neurones filled with the calcium-sensitive dye arsenazo III show a depression rather than facilitation to successive depolarizations in a train. The time course of these absorbance signals is consistent with the time-dependent depression of calcium current.6. Calibration of arsenazo III response amplitude indicates that the dye reports only about 1% of the calcium concentration increment expected from knowledge of cell volume and the charge carried by calcium current during a depolarizing pulse. This suggests that cytoplasmic buffering of free calcium must occur rapidly, on a time scale comparable to the response time of arsenazo III (about 1 msec) or more rapidly.7. The slow potassium tail current following a depolarizing pulse is calcium-dependent and probably provides an approximate index of the internal sub-membrane calcium concentration. Increments in this current after repetitive pulses display a slight progressive depression rather than facilitation.8. Since neither calcium currents nor the concentration transients show facilitation, we conclude that aequorin response facilitation is due to the non-linear dependence of aequorin photo-emissions on calcium concentration. This conclusion is supported by a finding that the very different kinetics of arsenazo III responses and aequorin responses can be reconciled by a simple model representing calcium accumulation and known response properties of the two indicator substances.9. In a train of impulses evoked by injecting depolarizing current into a neurone, the successive action potentials grow in duration. Nevertheless, a nearly constant calcium influx signalled by arsenazo III accompanies broadening action potentials.

Advances in Behavioral Biology, 1982

Intracellular Regulation of Ion Channels, 1992

Identified Neurons and Behavior of Arthropods, 1977

The Journal of Physiology, 1974

1. Changes in the post-activation excitability of crayfish motor nerve terminals were used to mea... more 1. Changes in the post-activation excitability of crayfish motor nerve terminals were used to measure afterpotentials that might be related to facilitation of transmitter release.2. The refractory period is followed by a period of supernormal excitability in which the threshold of nerve terminals drops to about 70% of its pre-activation level at about 15 msec following an impulse. The threshold returns exponentially to its pre-activation level with a time constant of about 25 msec at 13 degrees C. Such a supernormal excitability is rarely seen in pre-terminal nerve branches or in the main axon.3. Following a brief high-frequency tetanus the peak of the supernormal excitability is greater than that following a single impulse. At low temperature this peak is reduced and delayed, and the decay rate of the supernormal excitability is prolonged with a Q(10) of about 2.5.4. Depolarization of nerve terminals decreases, and hyperpolarization increases, the magnitude of the post-activation supernormal excitability.5. The magnitude of the supernormal excitability depends on the external potassium concentration, but not on sodium. In low calcium the peak supernormal excitability is often reduced. High calcium concentration and manganese ions have no effect, but cobalt abolishes the supernormal excitability, and its effects are only slightly reversible. Both cobalt and manganese reversibly block neuromuscular transmission.6. Strophanthidin has no effect on the post-activation supernormal excitability, but proteolytic enzymes reduce or abolish it, and hyperosmotic solutions also affect it.7. It is suggested that the action potential is followed by a depolarizing afterpotential in nerve terminals which is caused by a transient increase in the potassium concentration around the terminals. There is no evidence that afterpotentials in nerve terminals are related to facilitation in any way.

Neural Models of Plasticity, 1989

Mechanisms of Epileptogenesis, 1988

Neural Models of Plasticity, 1989

Model Neural Networks and Behavior, 1985

Encyclopedia of Life Sciences, 2001

Encyclopedia of Life Sciences, 2001

From Molecules to Networks, 2004

Neuron, Jan 17, 2005

In this issue of Neuron, Sara et al. find that spontaneously released miniature synaptic potentia... more In this issue of Neuron, Sara et al. find that spontaneously released miniature synaptic potentials arise from a pool of vesicles distinct from those released by neural activity. This modification of a basic tenet of the quantal hypothesis has important implications for the analysis of changes in synaptic transmission.

Neuron, Jan 19, 2003

The spontaneous fusion of vesicles at nerve terminals produces random miniature postsynaptic pote... more The spontaneous fusion of vesicles at nerve terminals produces random miniature postsynaptic potentials (quantal responses) that are thought to have little functional significance. In this issue of Neuron, Sharma and Vijayaraghavan provide evidence that exogenous signals can accelerate and synchronize the occurrence of quanta strongly enough to activate postsynaptic neurons in what may be a new way to transfer information across synapses.

From Molecules to Networks, 2014

From Molecules to Networks, 2014

The Journal of Physiology, 2001

The Journal of Physiology, 1974

1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in ... more 1. Experiments were conducted to test the hypothesis that facilitation of transmitter release in response to repetitive stimulation of the exciter motor axon to the crayfish claw opener muscle is due to an increase in the amplitude or duration of the action potential in presynaptic terminals. No consistent changes were found in the nerve terminal potential (n.t.p.) recorded extracellularly at synaptic sites on the surface of muscle fibres.2. Apparent changes in n.t.p. are attributed to three causes.(i) Some recordings are shown to be contaminated by non-specific muscle responses which grow during facilitation.(ii) Some averaged n.t.p.s exhibit opposite changes in amplitude and duration which suggest a change in the synchrony of presynaptic nerve impulses at different frequencies.(iii) Some changes in n.t.p. are blocked by gamma-methyl glutamate, an antagonist of the post-synaptic receptor, which suggests that these changes are caused by small muscle movements.3. The only change in n.t.p. believed to represent an actual change in the intracellular signal is a reduction in n.t.p. amplitude to the second of two stimuli separated by a brief interval.4. Tetra-ethyl ammonium ions increase synaptic transmission about 20% and prolong the n.t.p. about 15%. This result suggests that an increase in n.t.p. large enough to increase transmission by the several hundred per cent occurring during facilitation would be detected.5. The nerve terminals are electrically excitable, and most synaptic sites have a diphasic or triphasic n.t.p., which suggests that the motor neurone terminals are actively invaded by nerve impulses.6. When nerve impulses are blocked in tetrodotoxin, depolarization of nerve terminals increases the frequency of miniature excitatory junctional potentials (e.j.p.s), and a phasic e.j.p. can be evoked by large, brief depolarizing pulses. Responses to repetitive or paired depolarizations of constant amplitude and duration exhibit a facilitation similar to that of e.j.p.s evoked by nerve impulses.7. It is concluded that facilitation in the crayfish claw opener is not due to a change in the presynaptic action potential, but is due to some change at a later step in the depolarization-secretion process.

The Journal of Physiology, 1974

1. A quantitative description of facilitation in the crayfish claw opener muscle is presented. Th... more 1. A quantitative description of facilitation in the crayfish claw opener muscle is presented. The facilitation of a test response following one or more conditioning stimuli, and the growth of facilitation during a tetanus, are measured.2. In superficial central fibres facilitation following one or more impulses can be described as the sum of two components which are both maximum at the end of the conditioning train and decline simultaneously and exponentially with different time constants thereafter.3. During a tetanus, facilitation to successive stimuli grows more rapidly than is predicted by assuming that each impulse adds a constant facilitative effect to an accumulating total state of facilitation.4. Sufficiently large values of tetanic facilitation are predicted by a model which assumes that transmitter release is proportional to the nth power of a substance or factor accumulating in nerve terminals. But no single value of n predicts the correct rise of facilitation in a tetanus and the time course of its subsequent decline from the facilitation following a single spike.5. A model which assumes that the facilitative effects of successive spikes multiply in a tetanus predicts responses that are larger than those observed.6. The effects of varying the calcium concentration ([Ca(2+)]) on transmitter release and facilitation were studied. When a magnesium-EDTA buffering system is used to vary [Ca(2+)], transmitter release is found to be nearly linearly related to [Ca(2+)] in the range 0.1-13.5 mM.7. The magnitude and time course of facilitation during and following a tetanus are unaffected by varying [Ca(2+)] between 1.0 and 40 mM.8. The relation between ;steady-state' facilitation and stimulus frequency is also unaffected by changing [Ca(2+)], except that in high [Ca(2+)] transmitter release appears to saturate at high frequencies (above 30 Hz).9. The results are discussed in terms of the ;calcium accumulation' hypothesis of facilitation. The findings in crayfish appear to be qualitatively consistent with this hypothesis if certain modifications are made in the hypothesis.

The Journal of Physiology, 1980

1. When molluscan neural somata are filled with the calcium-indicating photo-protein aequorin and... more 1. When molluscan neural somata are filled with the calcium-indicating photo-protein aequorin and subjected to a 1 Hz train of depolarizing pulses (0.3 sec duration to + 15 mV) under voltage clamp, the successive photo-emissions due to calcium influx facilitate. The origin of this phenomenon was investigated in identified neurones from the abdominal ganglion of Aplysia californica.2. Since outward currents inactivate cumulatively in successive pulses, the effective depolarization increases due to a series resistance error. Elimination of this error by electronic compensation or pharmacological block of outward current reduced aequorin response facilitation by only about 30%, on the average.3. When voltage-dependent sodium and potassium currents are blocked in tetraethylammonium (TEA)-substituted zero-sodium sea water, the remaining inward calcium currents display no facilitation. On the contrary, a slow decline during a pulse and a slight progressive depression in successive pulses are observed. Barium-substitution for calcium in the same medium eliminates a small residual potassium current insensitive to external TEA. The remaining inward barium currents also display depression instead of facilitation.4. A non-pharmacological separation of calcium current was accomplished by measuring tail currents at the potassium equilibrium potential following depolarizing pulses. Calcium tail currents activate rapidly and then decline gradually and incompletely as depolarizing pulse duration is lengthened. Tail currents also show no evidence of facilitation; there is instead a slight depression of currents after successive pulses.5. Increments of optical absorbance in neurones filled with the calcium-sensitive dye arsenazo III show a depression rather than facilitation to successive depolarizations in a train. The time course of these absorbance signals is consistent with the time-dependent depression of calcium current.6. Calibration of arsenazo III response amplitude indicates that the dye reports only about 1% of the calcium concentration increment expected from knowledge of cell volume and the charge carried by calcium current during a depolarizing pulse. This suggests that cytoplasmic buffering of free calcium must occur rapidly, on a time scale comparable to the response time of arsenazo III (about 1 msec) or more rapidly.7. The slow potassium tail current following a depolarizing pulse is calcium-dependent and probably provides an approximate index of the internal sub-membrane calcium concentration. Increments in this current after repetitive pulses display a slight progressive depression rather than facilitation.8. Since neither calcium currents nor the concentration transients show facilitation, we conclude that aequorin response facilitation is due to the non-linear dependence of aequorin photo-emissions on calcium concentration. This conclusion is supported by a finding that the very different kinetics of arsenazo III responses and aequorin responses can be reconciled by a simple model representing calcium accumulation and known response properties of the two indicator substances.9. In a train of impulses evoked by injecting depolarizing current into a neurone, the successive action potentials grow in duration. Nevertheless, a nearly constant calcium influx signalled by arsenazo III accompanies broadening action potentials.

Advances in Behavioral Biology, 1982

Intracellular Regulation of Ion Channels, 1992

Identified Neurons and Behavior of Arthropods, 1977

The Journal of Physiology, 1974

1. Changes in the post-activation excitability of crayfish motor nerve terminals were used to mea... more 1. Changes in the post-activation excitability of crayfish motor nerve terminals were used to measure afterpotentials that might be related to facilitation of transmitter release.2. The refractory period is followed by a period of supernormal excitability in which the threshold of nerve terminals drops to about 70% of its pre-activation level at about 15 msec following an impulse. The threshold returns exponentially to its pre-activation level with a time constant of about 25 msec at 13 degrees C. Such a supernormal excitability is rarely seen in pre-terminal nerve branches or in the main axon.3. Following a brief high-frequency tetanus the peak of the supernormal excitability is greater than that following a single impulse. At low temperature this peak is reduced and delayed, and the decay rate of the supernormal excitability is prolonged with a Q(10) of about 2.5.4. Depolarization of nerve terminals decreases, and hyperpolarization increases, the magnitude of the post-activation supernormal excitability.5. The magnitude of the supernormal excitability depends on the external potassium concentration, but not on sodium. In low calcium the peak supernormal excitability is often reduced. High calcium concentration and manganese ions have no effect, but cobalt abolishes the supernormal excitability, and its effects are only slightly reversible. Both cobalt and manganese reversibly block neuromuscular transmission.6. Strophanthidin has no effect on the post-activation supernormal excitability, but proteolytic enzymes reduce or abolish it, and hyperosmotic solutions also affect it.7. It is suggested that the action potential is followed by a depolarizing afterpotential in nerve terminals which is caused by a transient increase in the potassium concentration around the terminals. There is no evidence that afterpotentials in nerve terminals are related to facilitation in any way.

Neural Models of Plasticity, 1989

Mechanisms of Epileptogenesis, 1988

Neural Models of Plasticity, 1989

Model Neural Networks and Behavior, 1985

Encyclopedia of Life Sciences, 2001

Encyclopedia of Life Sciences, 2001

From Molecules to Networks, 2004

Neuron, Jan 17, 2005

In this issue of Neuron, Sara et al. find that spontaneously released miniature synaptic potentia... more In this issue of Neuron, Sara et al. find that spontaneously released miniature synaptic potentials arise from a pool of vesicles distinct from those released by neural activity. This modification of a basic tenet of the quantal hypothesis has important implications for the analysis of changes in synaptic transmission.

Neuron, Jan 19, 2003

The spontaneous fusion of vesicles at nerve terminals produces random miniature postsynaptic pote... more The spontaneous fusion of vesicles at nerve terminals produces random miniature postsynaptic potentials (quantal responses) that are thought to have little functional significance. In this issue of Neuron, Sharma and Vijayaraghavan provide evidence that exogenous signals can accelerate and synchronize the occurrence of quanta strongly enough to activate postsynaptic neurons in what may be a new way to transfer information across synapses.

From Molecules to Networks, 2014

From Molecules to Networks, 2014

The Journal of Physiology, 2001