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The Journal of Neuroscience, August 15, 2007, 27(33):8927-8939; doi:10.1523/JNEUROSCI.2322-07.2007

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Cellular/Molecular
Protein Kinase C Regulates Local Synthesis and Secretion of a Neuropeptide Required for Activity-Dependent Long-Term Synaptic Plasticity

Jiang-Yuan Hu, Yang Chen, and Samuel Schacher

Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, New York 10032

Correspondence should be addressed to Samuel Schacher, Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032. Email: sms2{at}columbia.edu

Long-term facilitation (LTF) of sensory neuron synapses in Aplysia is produced by either nonassociative or associative stimuli. Nonassociative LTF can be produced by five spaced applications of serotonin (5-HT) and requires a phosphoinosotide 3-kinase (PI3K)-dependent and rapamycin-sensitive increase in the local synthesis of the sensory neuron neuropeptide sensorin and a protein kinase A (PKA)-dependent increase in the secretion of the newly synthesized sensorin. We report here that associative LTF produced by a single pairing of a brief tetanus with one application of 5-HT requires a rapid protein kinase C (PKC)-dependent and rapamycin-sensitive increase in local sensorin synthesis. This rapid increase in sensorin synthesis does not require PI3K activity or the presence of the sensory neuron cell body but does require the presence of the motor neuron. The secretion of newly synthesized sensorin by 2 h after stimulation requires both PKA and PKC activities to produce associative LTF because incubation with exogenous anti-sensorin antibody or the kinase inhibitors after tetanus plus 5-HT blocked LTF. The secreted sensorin leads to phosphorylation and translocation of p42/44 mitogen-activated protein kinase (MAPK) into the nuclei of the sensory neurons. Thus, different stimuli activating different signaling pathways converge by regulating the synthesis and release of a neuropeptide to produce long-term synaptic plasticity.

Key words: long-term facilitation; activity dependence; sensorin; local protein synthesis; protein kinase A; classical conditioning

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Received May 21, 2007; revised June 25, 2007; accepted July 2, 2007.

Correspondence should be addressed to Samuel Schacher, Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032. Email: sms2{at}columbia.edu

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				A. I. Hernandez, J. Wolk, J.-Y. Hu, J. Liu, T. Kurosu, J. H. Schwartz, and S. Schacher Poly-(ADP-Ribose) Polymerase-1 Is Necessary for Long-Term Facilitation in Aplysia J. Neurosci., July 29, 2009; 29(30): 9553 - 9562. [Abstract] [Full Text] [PDF]

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