title: Presynaptic residual calcium and synaptic facilitation at hippocampal synapses of mice with altered expression of SNAP-25.
abstract: Paired pulse facilitation (PPF) is a form of short-term synaptic plasticity that results from an interaction of residual presynaptic Ca(2+) ([Ca(2+)](res)), number of release-competent vesicles, and the sensitivity of the vesicle release mechanisms to Ca(2+). While PPF is predominant at hippocampal Schaffer collateral-CA1 (SC-CA1) synapses, facilitation is greater in adult mice (designated Tkneo) that over express an isoform of the plasma membrane-targeted SNARE protein, SNAP-25a, which is normally predominantly expressed in juvenile animals. SNAP-25 is essential for action potential-dependent neuroexocytosis, yet the significance of the shift between the alternatively spliced variants SNAP-25a and SNAP-25b is not fully understood. This alteration of a key component of the protein machinery required for neurotransmitter release in Tkneo mice, therefore, provides a useful tool to further investigate presynaptic mechanisms that influence short-term plasticity. To explore this link between SNAP-25 and PPF, we simultaneously measured postsynaptic potentials and presynaptic [Ca(2+)](res) during paired-pulses in adult Tkneo, heterozygote null (HET), and wild type (WT) mice. We demonstrate that enhanced PPF is maintained at mature hippocampal synapses of Tkneo mice that predominantly express SNAP-25a, and that [Ca(2+)](res) kinetics are altered at synapses of Tkneo and HET mice, both of which exhibit reduced levels of total SNAP-25 expression. To evaluate the role of SNAP-25 in short-term plasticity and [Ca(2+)](res) regulation, we applied a vesicular release probability model for neurotransmission. Our results suggest that the isoform expression and total level of SNAP-25 affect both [Ca(2+)](res) dynamics and the ability of releasable vesicles to enter into a facilitated state.
authors: Chessa S
authors: CS
authors: Scullin
authors: Lawrence C
authors: LC
authors: Tafoya
authors: Michael C
authors: MC
authors: Wilson
authors: L Donald
authors: LD
authors: Partridge
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000235:genetics; D000818:Animals; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25 / Q000172:deficiency*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; C494209:Snap25 protein, mouse; D026941:Sodium Channel Blockers; D050825:Synaptosomal-Associated Protein 25; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium