title: Pre- and postsynaptic mechanisms in Hebbian activity-dependent synapse modification.
abstract: We have used a three compartment tissue culture system that involved two separate populations of cholinergic neurons in the side compartments that converged on a common target population of myotubes in the center compartment. Activation of the axons from one population of neurons produced selective down-regulation of the synaptic inputs from the other neuronal population (when the two inputs innervated the same myotubes). The decrease in heterosynaptic inputs was mediated by protein kinase C (PKC). An activity-dependent action of protein kinase A (PKA) was associated with the stimulated input and this served to selectively stabilize this input. These changes associated with PKA and PKC activation were mediated by alterations in the number of acetylcholine receptors at the neuromuscular junction. These results suggest that neuromuscular electrical activity produces postsynaptic activation of both PKA and PKC, with the latter producing generalized synapse weakening and the former a selective synapse stabilization. Treatment of the neuronal cell body and axon to increase PKC activity by putting phorbal ester (PMA) in the side chamber did not affect synaptic transmission (with or without stimulation). By contrast, PKA blockade in the side compartment did produce an activity-dependent decrease in synaptic efficacy, which was due to a decrease in quantal release of neurotransmitter. Thus, when the synapse is activated, it appears that presynaptic PKA action is necessary to maintain transmitter output.
authors.affiliation: Section on Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20982, USA.
authors.forename: Min-Xu
authors.initials: MX
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Yang
authors.forename: Veronica
authors.initials: V
authors.lastname: Dunlap
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Nelson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004558:Electric Stimulation; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D009469:Neuromuscular Junction / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013569:Synapses / Q000201:enzymology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D011950:Receptors, Cholinergic; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C