 |
Next Article 
Journal of Neuroscience, Vol 16, 425-435, Copyright © 1996 by Society for Neuroscience
Presynaptic facilitation revisited: state and time dependence
JH Byrne and ER Kandel
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston 77030, USA.
The mechanisms underlying short-term presynaptic facilitation, the
enhancement of transmitter release from sensory neurons in Aplysia, induced
by serotonin (5-HT), can be divided into two categories: (1) changes in
ionic conductances leading to spike broadening and enhancement of Ca2+
influx; and (2) actions on the machinery for transmitter release that are
independent of spike broadening and the resulting increases in Ca2+ influx.
Spike broadening and the associated enhancement of excitability are induced
by the modulation of K+ conductances in the sensory neuron. The cellular
mechanisms that contribute to the enhancement of release that is
independent of spike broadening are not known and may involve vesicle
mobilization or other steps in exocytotic release. These two facilitatory
actions of 5-HT are mediated by at least two second-messenger-activated
protein kinase systems, protein kinase A (PKA) and protein kinase C (PKC).
These two second-messenger cascades overlap in their contributions to
synaptic facilitation. However, their relative contributions to enhancement
of transmitter release are not simply synergistic but are state- and time-
dependent. The state dependence is a reflection of the synapse's previous
history of activity. When the synapse is rested (and not depressed), a
brief pulse of 5-HT (lasting from 10 sec to 5 min) produces its actions
primarily through PKA via both spike broadening- dependent and -independent
mechanisms. The broadening primarily involves the modulation of a
voltage-dependent K+ current, IKV, with a small contribution by a
voltage-independent K+ current, IKS. By contrast, the enhancement of
excitability is mediated primarily by the modulation of IKS. As the synapse
becomes depressed with repeated activity, the contribution of PKC becomes
progressively more important. As is the case with PKA, PKC produces its
action both by broadening the spike via modulation of IKV and by a spike
broadening-independent mechanism. In addition to being state-dependent, the
mechanisms of facilitation are time-dependent. There are differences in the
response to 5-HT when it is given briefly to produce short-term
facilitation or when the exposure is prolonged. When exposure is brief
(< or = 5 min), PKA dominates. When exposure is prolonged (10-20 min),
PKC becomes dominant as it is with depressed synapses. Thus, synaptic
plasticity appears to be expressed in several overlapping time domains, and
the transition between very short-term facilitation and various
intermediate duration phases seems to involve interactive processes between
the kinases.
This article has been cited by other articles:

|
 |

|
 |
 
F. Alnajjar and K. Murase
A Simple Aplysia-Like Spiking Neural Network to Generate Adaptive Behavior in Autonomous Robots
Adaptive Behavior,
October 1, 2008;
16(5):
306 - 324.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
S. H. C. Lee, K. Taylor, and F. B. Krasne
Reciprocal Stimulation of Decay Between Serotonergic Facilitation and Depression of Synaptic Transmission
J Neurophysiol,
August 1, 2008;
100(2):
1113 - 1126.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. A. Farah, I. Nagakura, D. Weatherill, X. Fan, and W. S. Sossin
Physiological Role for Phosphatidic Acid in the Translocation of the Novel Protein Kinase C Apl II in Aplysia Neurons
Mol. Cell. Biol.,
August 1, 2008;
28(15):
4719 - 4733.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Fulton, M. C. Condro, K. Pearce, and D. L. Glanzman
The Potential Role of Postsynaptic Phospholipase C Activity in Synaptic Facilitation and Behavioral Sensitization in Aplysia
J Neurophysiol,
July 1, 2008;
100(1):
108 - 116.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Fioravante, R.-Y. Liu, A. K. Netek, L. J. Cleary, and J. H. Byrne
Synapsin Regulates Basal Synaptic Strength, Synaptic Depression, and Serotonin-Induced Facilitation of Sensorimotor Synapses in Aplysia
J Neurophysiol,
December 1, 2007;
98(6):
3568 - 3580.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Antonov, T. Ha, I. Antonova, L. L. Moroz, and R. D. Hawkins
Role of Nitric Oxide in Classical Conditioning of Siphon Withdrawal in Aplysia
J. Neurosci.,
October 10, 2007;
27(41):
10993 - 11002.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Sakurai, R. J. Calin-Jageman, and P. S. Katz
Potentiation Phase of Spike Timing-Dependent Neuromodulation by a Serotonergic Interneuron Involves an Increase in the Fraction of Transmitter Release
J Neurophysiol,
October 1, 2007;
98(4):
1975 - 1987.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. L. P. Habets and J. G. G. Borst
Dynamics of the readily releasable pool during post-tetanic potentiation in the rat calyx of Held synapse
J. Physiol.,
June 1, 2007;
581(2):
467 - 478.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. S. Sossin
Isoform specificity of protein kinase Cs in synaptic plasticity
Learn. Mem.,
April 2, 2007;
14(4):
236 - 246.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I-F. Peng and C.-F. Wu
Drosophila cacophony Channels: A Major Mediator of Neuronal Ca2+ Currents and a Trigger for K+ Channel Homeostatic Regulation
J. Neurosci.,
January 31, 2007;
27(5):
1072 - 1081.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. G. Antzoulatos and J. H. Byrne
Long-Term Sensitization Training Produces Spike Narrowing in Aplysia Sensory Neurons
J. Neurosci.,
January 17, 2007;
27(3):
676 - 683.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Marinesco, N. Wickremasinghe, and T. J. Carew
Regulation of Behavioral and Synaptic Plasticity by Serotonin Release within Local Modulatory Fields in the CNS of Aplysia
J. Neurosci.,
December 6, 2006;
26(49):
12682 - 12693.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Isiegas, A. Park, E. R. Kandel, T. Abel, and K. M. Lattal
Transgenic Inhibition of Neuronal Protein Kinase A Activity Facilitates Fear Extinction
J. Neurosci.,
December 6, 2006;
26(49):
12700 - 12707.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Heyland and L. L. Moroz
Signaling mechanisms underlying metamorphic transitions in animals
Integr. Comp. Biol.,
December 1, 2006;
46(6):
743 - 759.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Vervaeke, N. Gu, C. Agdestein, H. Hu, and J. F. Storm
Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release
J. Physiol.,
October 1, 2006;
576(1):
235 - 256.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-A Lee, S.-H. Lee, C. Lee, D.-J. Chang, Y. Lee, H. Kim, Y.-H. Cheang, H.-G. Ko, Y.-S. Lee, H. Jun, et al.
PKA-activated ApAF-ApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation
J. Cell Biol.,
September 11, 2006;
174(6):
827 - 838.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Zhao, K. Leal, C. Abi-Farah, K. C. Martin, W. S. Sossin, and M. Klein
Isoform Specificity of PKC Translocation in Living Aplysia Sensory Neurons and a Role for Ca2+-Dependent PKC APL I in the Induction of Intermediate-Term Facilitation.
J. Neurosci.,
August 23, 2006;
26(34):
8847 - 8856.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. D. Hawkins, E. R. Kandel, and C. H. Bailey
Molecular Mechanisms of Memory Storage in Aplysia
Biol. Bull.,
June 1, 2006;
210(3):
174 - 191.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Kuzirian, H. T. Epstein, C. J. Gagliardi, T. J. Nelson, M. Sakakibara, C. Taylor, A. B. Scioletti, and D. L. Alkon
Bryostatin Enhancement of Memory in Hermissenda
Biol. Bull.,
June 1, 2006;
210(3):
201 - 214.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Diaz-Rios and M. W. Miller
Target-Specific Regulation of Synaptic Efficacy in the Feeding Central Pattern Generator of Aplysia: Potential Substrates for Behavioral Plasticity?
Biol. Bull.,
June 1, 2006;
210(3):
215 - 229.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. J. Ha, A. B. Kohn, Y. V. Bobkova, and L. L. Moroz
Molecular Characterization of NMDA-Like Receptors in Aplysia and Lymnaea: Relevance to Memory Mechanisms
Biol. Bull.,
June 1, 2006;
210(3):
255 - 270.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. L. Glanzman
The Cellular Mechanisms of Learning in Aplysia: Of Blind Men and Elephants
Biol. Bull.,
June 1, 2006;
210(3):
271 - 279.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. D. Hawkins, T. E. Cohen, and E. R. Kandel
Dishabituation in Aplysia can involve either reversal of habituation or superimposed sensitization
Learn. Mem.,
May 1, 2006;
13(3):
397 - 403.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Dumitriu, J. E. Cohen, Q. Wan, A. M. Negroiu, and T. W. Abrams
Serotonin Receptor Antagonists Discriminate Between PKA- and PKC-Mediated Plasticity in Aplysia Sensory Neurons
J Neurophysiol,
April 1, 2006;
95(4):
2713 - 2720.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Sakurai, N. R. Darghouth, R. J. Butera, and P. S. Katz
Serotonergic Enhancement of a 4-AP-Sensitive Current Mediates the Synaptic Depression Phase of Spike Timing-Dependent Neuromodulation
J. Neurosci.,
February 15, 2006;
26(7):
2010 - 2021.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Seino and T. Shibasaki
PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis
Physiol Rev,
October 1, 2005;
85(4):
1303 - 1342.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Park, J.-A Lee, C. Lee, M.-J. Kim, D.-J. Chang, H. Kim, S.-H. Lee, Y.-S. Lee, and B.-K. Kaang
An Aplysia Type 4 Phosphodiesterase Homolog Localizes at the Presynaptic Terminals of Aplysia Neuron and Regulates Synaptic Facilitation
J. Neurosci.,
September 28, 2005;
25(39):
9037 - 9045.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. A. Mohamed, W. Yao, D. Fioravante, P. D. Smolen, and J. H. Byrne
cAMP-response Elements in Aplysia creb1, creb2, and Ap-uch Promoters: IMPLICATIONS FOR FEEDBACK LOOPS MODULATING LONG TERM MEMORY
J. Biol. Chem.,
July 22, 2005;
280(29):
27035 - 27043.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. A. Phares and J. H. Byrne
Analysis of 5-HT-Induced Short-Term Facilitation at Aplysia Sensorimotor Synapse During Bursts: Increased Synaptic Gain That Does Not Require ERK Activation
J Neurophysiol,
July 1, 2005;
94(1):
871 - 877.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Khoutorsky and M. E. Spira
Calcium-activated proteases are critical for refilling depleted vesicle stores in cultured sensory-motor synapses of Aplysia
Learn. Mem.,
July 1, 2005;
12(4):
414 - 422.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q. Li, A. C. Roberts, and D. L. Glanzman
Synaptic Facilitation and Behavioral Dishabituation in Aplysia: Dependence on Release of Ca2+ from Postsynaptic Intracellular Stores, Postsynaptic Exocytosis, and Modulation of Postsynaptic AMPA Receptor Efficacy
J. Neurosci.,
June 8, 2005;
25(23):
5623 - 5637.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. D. Runyan and P. K. Dash
Distinct prefrontal molecular mechanisms for information storage lasting seconds versus minutes
Learn. Mem.,
May 1, 2005;
12(3):
232 - 238.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Gasque, P. Labarca, E. Reynaud, and A. Darszon
Shal and Shaker Differential Contribution to the K+ Currents in the Drosophila Mushroom Body Neurons
J. Neurosci.,
March 2, 2005;
25(9):
2348 - 2358.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. K. Reynolds, M. A. Schade, and K. G. Miller
Convergent, RIC-8-Dependent G{alpha} Signaling Pathways in the Caenorhabditis elegans Synaptic Signaling Network
Genetics,
February 1, 2005;
169(2):
651 - 670.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Khabour, J. Levenson, L. C. Lyons, L. S. Kategaya, J. Chin, J. H. Byrne, and A. Eskin
Coregulation of Glutamate Uptake and Long-Term Sensitization in Aplysia
J. Neurosci.,
October 6, 2004;
24(40):
8829 - 8837.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Wainwright, J. H. Byrne, and L. J. Cleary
Dissociation of Morphological and Physiological Changes Associated With Long-Term Memory in Aplysia
J Neurophysiol,
October 1, 2004;
92(4):
2628 - 2632.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y.-J. Sung, E. T. Walters, and R. T. Ambron
A Neuronal Isoform of Protein Kinase G Couples Mitogen-Activated Protein Kinase Nuclear Import to Axotomy-Induced Long-Term Hyperexcitability in Aplysia Sensory Neurons
J. Neurosci.,
August 25, 2004;
24(34):
7583 - 7595.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Cohen-Armon, L. Visochek, A. Katzoff, D. Levitan, A. J. Susswein, R. Klein, M. Valbrun, and J. H. Schwartz
Long-Term Memory Requires PolyADP-ribosylation
Science,
June 18, 2004;
304(5678):
1820 - 1822.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. P. Brown, P. K. Safo, and W. G. Regehr
Endocannabinoids Inhibit Transmission at Granule Cell to Purkinje Cell Synapses by Modulating Three Types of Presynaptic Calcium Channels
J. Neurosci.,
June 16, 2004;
24(24):
5623 - 5631.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. M. Sherff and T. J. Carew
Parallel somatic and synaptic processing in the induction of intermediate-term and long-term synaptic facilitation in Aplysia
PNAS,
May 11, 2004;
101(19):
7463 - 7468.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Susswein, A. Katzoff, N. Miller, and I. Hurwitz
Nitric Oxide and Memory
Neuroscientist,
April 1, 2004;
10(2):
153 - 162.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Liu, J.-Y. Hu, S. Schacher, and J. H. Schwartz
The Two Regulatory Subunits of Aplysia cAMP-Dependent Protein Kinase Mediate Distinct Functions in Producing Synaptic Plasticity
J. Neurosci.,
March 10, 2004;
24(10):
2465 - 2474.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. W. Jacklet and D. G. Tieman
Nitric Oxide and Histamine Induce Neuronal Excitability by Blocking Background Currents in Neuron MCC of Aplysia
J Neurophysiol,
February 1, 2004;
91(2):
656 - 665.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. Bristol, M. A. Sutton, and T. J. Carew
Neural Circuit of Tail-Elicited Siphon Withdrawal in Aplysia. I. Differential Lateralization of Sensitization and Dishabituation
J Neurophysiol,
February 1, 2004;
91(2):
666 - 677.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. Bristol, S. Marinesco, and T. J. Carew
Neural Circuit of Tail-Elicited Siphon Withdrawal in Aplysia. II. Role of Gated Inhibition in Differential Lateralization of Sensitization and Dishabituation
J Neurophysiol,
February 1, 2004;
91(2):
678 - 692.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Sakurai and P. S. Katz
Spike Timing-Dependent Serotonergic Neuromodulation of Synaptic Strength Intrinsic to a Central Pattern Generator Circuit
J. Neurosci.,
November 26, 2003;
23(34):
10745 - 10755.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Yang, X.-p. He, J. Russell, and B. Lu
Ca2+ influx-independent synaptic potentiation mediated by mitochondrial Na+-Ca2+ exchanger and protein kinase C
J. Cell Biol.,
November 10, 2003;
163(3):
511 - 523.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. T. Birmingham and D. L. Tauck
Neuromodulation in invertebrate sensory systems: from biophysics to behavior
J. Exp. Biol.,
October 15, 2003;
206(20):
3541 - 3546.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. A. Phares, E. G. Antzoulatos, D. A. Baxter, and J. H. Byrne
Burst-Induced Synaptic Depression and Its Modulation Contribute to Information Transfer at Aplysia Sensorimotor Synapses: Empirical and Computational Analyses
J. Neurosci.,
September 10, 2003;
23(23):
8392 - 8401.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. G. Antzoulatos, L. J. Cleary, A. Eskin, D. A. Baxter, and J. H. Byrne
Desensitization of Postsynaptic Glutamate Receptors Contributes to High-Frequency Homosynaptic Depression of Aplysia Sensorimotor Connections
Learn. Mem.,
September 1, 2003;
10(5):
309 - 313.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Meneses
A Pharmacological Analysis of an Associative Learning Task: 5-HT1 to 5-HT7 Receptor Subtypes Function on a Pavlovian/Instrumental Autoshaped Memory
Learn. Mem.,
September 1, 2003;
10(5):
363 - 372.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Barbas, L. DesGroseillers, V. F. Castellucci, T. J. Carew, and S. Marinesco
Multiple Serotonergic Mechanisms Contributing to Sensitization in Aplysia: Evidence of Diverse Serotonin Receptor Subtypes
Learn. Mem.,
September 1, 2003;
10(5):
373 - 386.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Buttner and S. A. Siegelbaum
Antagonistic Modulation of a Hyperpolarization-Activated Cl- Current in Aplysia Sensory Neurons by SCPB and FMRFamide
J Neurophysiol,
August 1, 2003;
90(2):
586 - 598.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Nakhost, G. Houeland, V. F. Castellucci, and W. S. Sossin
Differential Regulation of Transmitter Release by Alternatively Spliced Forms of Synaptotagmin I
J. Neurosci.,
July 16, 2003;
23(15):
6238 - 6244.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. T. Tamse, Y. Xu, H. Song, L. Nie, and E. N. Yamoah
Protein Kinase A Mediates Voltage-Dependent Facilitation of Ca2+ Current in Presynaptic Hair Cells in Hermissenda crassicornis
J Neurophysiol,
March 1, 2003;
89(3):
1718 - 1726.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. E. Cohen, C. U. Onyike, V. L. McElroy, A. H. Lin, and T. W. Abrams
Pharmacological Characterization of an Adenylyl Cyclase-Coupled 5-HT Receptor in Aplysia: Comparison With Mammalian 5-HT Receptors
J Neurophysiol,
March 1, 2003;
89(3):
1440 - 1455.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. M. Talley, J. E. Sirois, Q. Lei, and D. A. Bayliss
Two-Pore-Domain (Kcnk) Potassium Channels: Dynamic Roles in Neuronal Function
Neuroscientist,
February 1, 2003;
9(1):
46 - 56.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
G. S. Mitchell and S. M. Johnson
Plasticity in Respiratory Motor Control: Invited Review: Neuroplasticity in respiratory motor control
J Appl Physiol,
January 1, 2003;
94(1):
358 - 374.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Pepio, G. L. Thibault, and W. S. Sossin
Phosphoinositide-dependent Kinase Phosphorylation of Protein Kinase C Apl II Increases during Intermediate Facilitation in Aplysia
J. Biol. Chem.,
September 27, 2002;
277(40):
37116 - 37123.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Hasuo, T. Matsuoka, and T. Akasu
Activation of Presynaptic 5-Hydroxytryptamine 2A Receptors Facilitates Excitatory Synaptic Transmission via Protein Kinase C in the Dorsolateral Septal Nucleus
J. Neurosci.,
September 1, 2002;
22(17):
7509 - 7517.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|