High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor
2014; 17 (6): 884-889
Presynaptic long-term plasticity.
Frontiers in synaptic neuroscience
2013; 5: 8-?
Accurate optical reporting of electrical activity in genetically defined neuronal populations is a long-standing goal in neuroscience. We developed Accelerated Sensor of Action Potentials 1 (ASAP1), a voltage sensor design in which a circularly permuted green fluorescent protein is inserted in an extracellular loop of a voltage-sensing domain, rendering fluorescence responsive to membrane potential. ASAP1 demonstrated on and off kinetics of ∼2 ms, reliably detected single action potentials and subthreshold potential changes, and tracked trains of action potential waveforms up to 200 Hz in single trials. With a favorable combination of brightness, dynamic range and speed, ASAP1 enables continuous monitoring of membrane potential in neurons at kilohertz frame rates using standard epifluorescence microscopy.
View details for DOI 10.1038/nn.3709
View details for Web of Science ID 000336638000025
Munc13-1 Is Required for Presynaptic Long-Term Potentiation
JOURNAL OF NEUROSCIENCE
2011; 31 (33): 12053-12057
Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity.
View details for DOI 10.3389/fnsyn.2013.00008
View details for PubMedID 24146648
Acute In Vivo Genetic Rescue Demonstrates That Phosphorylation of RIM1 alpha Serine 413 Is Not Required for Mossy Fiber Long-Term Potentiation
JOURNAL OF NEUROSCIENCE
2010; 30 (7): 2542-2546
Long-lasting forms of synaptic plasticity involve modification of presynaptic strength in many brain regions. Although a presynaptic site for expression is well established, the detailed molecular mechanisms that lead to sustained changes in neurotransmitter release remain unclear. Here, we use acute in vivo genetic manipulation of synaptic proteins to investigate the molecular basis for presynaptic long-term potentiation (LTP) at hippocampal mossy fiber synapses. Munc13 proteins are active zone proteins that are essential for synaptic vesicle priming and neurotransmitter release. Munc13 proteins also interact with RIM1?, an active zone protein required for presynaptic long-term plasticity. By taking advantage of the observation that the RIM-binding domain of Munc13 is separable from the domain that is required for neurotransmitter release, we selectively tested whether Munc13-1 is an effector for RIM1? in presynaptic LTP. Our results provide the first evidence for the involvement of Munc13-1 in presynaptic long-term synaptic plasticity. We further demonstrate that the interaction between RIM1? and Munc13-1 is required for this plasticity. These results advance our understanding of the molecular mechanisms of presynaptic plasticity and suggest that modulation of vesicle priming may provide the cellular substrate for expression of LTP at mossy fiber synapses.
View details for DOI 10.1523/JNEUROSCI.2276-11.2011
View details for Web of Science ID 000293950300032
View details for PubMedID 21849565
While presynaptic, protein kinase A (PKA)-dependent, long-term plasticity has been described in numerous brain regions, the target(s) of PKA and the molecular mechanisms leading to sustained changes in neurotransmitter release remain elusive. Here, we acutely reconstitute mossy fiber long-term potentiation (mfLTP) de novo in the mature brains of mutant mice that normally lack this form of plasticity. These results demonstrate that RIM1alpha, a presynaptic scaffold protein and a potential PKA target, can support mfLTP independent of a role in brain development. Using this approach, we study two mutations of RIM1alpha (S413A and V415P) and conclude that PKA-phosphorylation-dependent signaling by RIM1alpha serine 413 is not required for mfLTP, consistent with conclusions reached from the study of RIM1alpha S413A knockin mice. Together, these results provide insights into the mechanism of mossy fiber LTP and demonstrate a useful acute approach to genetically manipulate mossy fiber synapses in the mature brain.
View details for DOI 10.1523/JNEUROSCI.4285-09.2010
View details for Web of Science ID 000274599600017
View details for PubMedID 20164339