Differential Control of Vesicle Priming and Short-Term Plasticity by Munc13 Isoforms

• Published in: Neuron (Cambridge, Mass.) Mass.), 2002-01, Vol.33 (3), p.411-424
• Main Authors: Rosenmund, Christian, Sigler, Albrecht, Augustin, Iris, Reim, Kerstin, Brose, Nils, Rhee, Jeong-Seop
• Format: Article
• Language: English
• Subjects: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Animals; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Calcium - metabolism; Cells, Cultured; Dizocilpine Maleate - pharmacology; Electric Stimulation; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - physiology; Experiments; Glutamic Acid - metabolism; Hippocampus - cytology; Hippocampus - metabolism; Insects; Intracellular Signaling Peptides and Proteins; Kinases; Mice; Mice, Knockout; Munc13 protein; N-Methylaspartate - pharmacology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neuronal Plasticity - physiology; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Protein Isoforms - genetics; Protein Isoforms - metabolism; Synaptic Transmission - physiology; Synaptic Vesicles - metabolism; Thiazoles - pharmacology; Thiazolidines; Transmitters; Type C Phospholipases - antagonists & inhibitors; Type C Phospholipases - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(02)00568-8

Presynaptic short-term plasticity is an important adaptive mechanism regulating synaptic transmitter release at varying action potential frequencies. However, the underlying molecular mechanisms are unknown. We examined genetically defined and functionally unique axonal subpopulations of synapses in excitatory hippocampal neurons that utilize either Munc13-1 or Munc13-2 as synaptic vesicle priming factor. In contrast to Munc13-1-dependent synapses, Munc13-2-driven synapses show pronounced and transient augmentation of synaptic amplitudes following high-frequency stimulation. This augmentation is caused by a Ca 2+-dependent increase in release probability and releasable vesicle pool size, and requires phospholipase C activity. Thus, differential expression of Munc13 isoforms at individual synapses represents a general mechanism that controls short-term plasticity and contributes to the heterogeneity of synaptic information coding.