An Electrophysiological Investigation of the SNAP-25 Isoforms as Possible Regulators of Short-term Synaptic Plasticity
نویسنده
چکیده
Neurons communicate with each other primarily through chemical synapses, where electrical signals are converted into chemical signals and then back to electrical signals. In the synapse, the electrical signal is transformed to a chemical signal through fusion of neurotransmitter-containing vesicles with the presynaptic plasma membrane. This regulated transmitter release is mainly promoted by a presynaptic core protein complex comprised of vesicular VAMP-2/synaptobrevin, plasma membraneassociated syntaxin 1A and synaptosomal-associated protein of 25 kDa (SNAP-25). SNAP-25 is normally expressed in neurons as two alternative isoforms, SNAP-25a and SNAP-25b. The expression of these isoforms is different during development with SNAP-25a predominating early and SNAP-25b becoming dominant in week one and three after birth. Although these basic molecular components that promote regulated neurotransmitter release are well established, the contribution of these proteins as regulators of synaptic plasticity is less well understood. The aim of this thesis has been to investigate if and how short-term synaptic plasticity is altered in genetically modified mice that lack SNAP-25b in comparison to wildtype mice expressing both SNAP-25a and SNAP-25b. To examine this, Paired-Pulse Facilitation (PPF) experiments were performed in brain slices from these different mice. PPF is a form of short-term, activity-dependent synaptic plasticity common to many chemical synapses. The experiments were performed by stimulation of presynaptic axon bundles with two electrical pulses in rapid succession while neurotransmitter-induced postsynaptic responses were measured by whole-cell voltage clamp. The obtained results indicate that SNAP-25b deficient mice show a significantly reduced facilitation. This suggests that SNAP-25b acts presynaptically as a positive regulator of short-term synaptic plasticity. The developmental shift from SNAP-25a to mainly SNAP-25b expression, mediated by alternative splicing, contributes to synaptic transmission by enhancing the facilitory process of neurotransmitter release. En elektrofysiologisk undersökning av SNAP-25 isoformerna som möjliga regulatorer av synaptisk kort-tids plasticitet
منابع مشابه
Developmentally regulated switch in alternatively spliced SNAP-25 isoforms alters facilitation of synaptic transmission.
Although the basic molecular components that promote regulated neurotransmitter release are well established, the contribution of these proteins as regulators of the plasticity of neurotransmission and refinement of synaptic connectivity during development is elaborated less fully. For example, during the period of synaptic growth and maturation in brain, the expression of synaptosomal protein ...
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