Presynaptic residual calcium and synaptic facilitation at hippocampal synapses of mice with altered expression of SNAP-25

Paired pulse facilitation (PPF) is a form of short-term synaptic plasticity that results from an interaction of residual presynaptic Ca2 + ([Ca2 +]res), number of release-competent vesicles, and the sensitivity of the vesicle release mechanisms to Ca2 +. 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 [Ca2 +]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 [Ca2 +]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 [Ca2 +]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 [Ca2 +]res dynamics and the ability of releasable vesicles to enter into a facilitated state.

► Facilitation and [Ca2 +]res were studied in SNAP-25a overexpressing mutant mice.
► SNAP-25 isoform or total level did not affect initial fEPSP amplitude.
► SNAP-25 isoform affected [Ca2 +]res during the first and second of paired pulses.
► Modeling studies suggest a role of SNAP-25 in [Ca2 +]i buffering.