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Essential Role of Somatic and Synaptic Protein Synthesis and Axonal Transport in Long-Term Synapse-Specific Facilitation at Distal Sensorimotor Connections in Aplysia

Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112

^* To whom correspondence should be addressed, at Department of Bioengineering, University of Utah, 20 S 2030 East, Room 506 BPRB, Salt Lake City, UT 84112-9458. E-mail: greg.clark{at}utah.edu

To investigate further the cellular mechanisms underlying long-term facilitation (LTF) and long-term synapse-specific facilitation (LTSSF), we studied the role of axonal transport and somatic and synaptic protein synthesis at proximal and distal synapses of Aplysia siphon sensory neurons (SNs). The long soma-synapse distances (2.5 to 3 cm) of the SN distal synapses impose important temporal and mechanistic constraints on long-term facilitation and on intracellular signaling. Excitatory postsynaptic potentials (EPSPs) evoked by SNs in central and peripheral siphon motor neurons were used to assay LTF 24–30 h after various pharmacological treatments. Inhibition of protein synthesis via anisomysin application at either the SN soma or distal synapses blocked the induction of LTF and LTSSF normally produced by synaptic application of the facilitating transmitter serotonin (5-hydroxytryptamine). Further, disruption of axonal transport by application of nocodazole to the isolated siphon nerve completely blocked LTF at distal synapses. These results indicate an essential role for somatic and synaptic protein synthesis and active axonal transport in LTSSF at distal synapses, and raise intriguing questions for current synaptic marking/capture models of synapse specificity and LTF.

Abbreviations: ANOVA, analysis of variance • ASW, artificial seawater • C-Aniso, central anisomycin • CMN, central motor neuron • EPSP, excitatory postsynaptic potential • 5-HT, 5-hydroxytryptamine, serotonin • LTF, long-term facilitation • LTP, long-term potentiation • LTSSF, long-term synapse-specific facilitation • MN, motor neuron • P-Aniso, peripheral anisomycin • PMN, peripheral motor neuron • SN, sensory neuron

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