Reaction times (RTs) are assumed to reflect the underlying computations required for making decisions and preparing actions. However, recent work has shown that movements can be initiated earlier than typically expressed without affecting performance; hence, the RT may be modulated by factors other than computation time. Consistent with that view, we demonstrated that RTs are influenced by prior experience: when a previously performed task required a specific RT to support task success, this biased the RTs in future tasks. This effect is similar to the use-dependent biases observed for other movement parameters such as speed or direction. Moreover, kinematic analyses revealed that these RT biases could occur without changing the underlying computations required to perform the action. Thus the RT is not solely determined by computational requirements but is an independent parameter that can be habitually set by prior experience.
- Adrian M Haith
- John W Krakauer
- Jeff Goldsmith
- Jeff Goldsmith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: All participants provided written informed consent and were naive to the purposes of the study. Experimental methods were approved by the Johns Hopkins University School of Medicine institutional review board.
- Jennifer L Raymond, Stanford School of Medicine, United States
© 2017, Wong et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The Ca2+ sensor synaptotagmin-1 and the SNARE complex cooperate to trigger neurotransmitter release. Structural studies elucidated three distinct synaptotagmin-1-SNARE complex binding modes involving ‘polybasic’, ‘primary’ and ‘tripartite’ interfaces of synaptotagmin-1. We investigated these interactions using NMR and fluorescence spectroscopy. Synaptotagmin-1 binds to the SNARE complex through the polybasic and primary interfaces in solution. Ca2+-free synaptotagmin-1 binds to SNARE complexes anchored on PIP2-containing nanodiscs. R398Q/R399Q and E295A/Y338W mutations at the primary interface, which strongly impair neurotransmitter release, disrupt and enhance synaptotagmin-1-SNARE complex binding, respectively. Ca2+ induces tight binding of synaptotagmin-1 to PIP2-containing nanodiscs, disrupting synaptotagmin-1-SNARE interactions. Specific effects of mutations in the polybasic region on Ca2+-dependent synaptotagmin-1-PIP2-membrane interactions correlate with their effects on release. Our data suggest that synaptotagmin-1 binds to the SNARE complex through the primary interface and that Ca2+ releases this interaction, inducing PIP2/membrane binding and allowing cooperation between synaptotagmin-1 and the SNAREs in membrane fusion to trigger release.
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