Dendritic position is a major determinant of presynaptic strength

Jong, Arthur P.H. de; Schmitz, Sabine; Toonen, Ruud F.; Verhage, Matthijs

doi:10.1083/jcb.201112135

Cited by 24 publications

(24 citation statements)

References 56 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides we found that the soma has absolutely the larger synapses with the larger recycling pool and the higher spontaneous release, but if spontaneous and evoked turnover is normalized on the size of the synapse, the relative release is higher at the processes. Recent publications found a distance from soma dependency of synapse size and evoked release at the processes [20,21]. In accordance with evoked release [21], spontaneous release declined along the processes with increasing distance to the soma (Additional file 1: Figure S5A), but remained constant, if spontaneous release was normalized on synapse size (Additional file 1: Figure S5B).…”

Section: Conclusion and Discussionsupporting

confidence: 66%

“…Recent publications found a distance from soma dependency of synapse size and evoked release at the processes [20,21]. In accordance with evoked release [21], spontaneous release declined along the processes with increasing distance to the soma (Additional file 1: Figure S5A), but remained constant, if spontaneous release was normalized on synapse size (Additional file 1: Figure S5B). Our functional measurements indicated, that both forms of release exhibit the same relationship regarding distance from the soma with smaller, but more effective synapses at the process [11].…”

Section: Conclusion and Discussionsupporting

confidence: 66%

See 1 more Smart Citation

Common strength and localization of spontaneous and evoked synaptic vesicle release sites

et al. 2014

View full text Add to dashboard Cite

BackgroundDifferent pools and functions have recently been attributed to spontaneous and evoked vesicle release. Despite the well-established function of evoked release, the neuronal information transmission, the origin as well as the function of spontaneously fusing synaptic vesicles have remained elusive. Recently spontaneous release was found to e.g. regulate postsynaptic protein synthesis or has been linked to depressive disorder. Nevertheless the strength and cellular localization of this release form was neglected so far, which are both essential parameters in neuronal information processing.FindingsHere we show that the complete recycling pool can be turned over by spontaneous trafficking and that spontaneous fusion rates critically depend on the neuronal localization of the releasing synapse. Thereby, the distribution equals that of evoked release so that both findings demonstrate a uniform regulation of these fusion modes.ConclusionsIn contrast to recent works, our results strengthen the assumption that identical vesicles are used for evoked and spontaneous release and extended the knowledge about spontaneous fusion with respect to its amount and cellular localization. Therefore our data supported the hypothesis of a regulatory role of spontaneous release in neuronal outgrowth and plasticity as neurites secrete neurotransmitters to initiate process outgrowth of a possible postsynaptic neuron to form a new synaptic connection.

show abstract

Section: Conclusion and Discussionsupporting

confidence: 66%

Section: Conclusion and Discussionsupporting

confidence: 66%

Common strength and localization of spontaneous and evoked synaptic vesicle release sites

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The integration of presynaptic and postsynaptic events is strongly influenced by their location along the dendritic arbor. Postsynaptic elements at distal synapses have the highest gain for integration, while presynaptic elements located at the distal end have the least gain (de Jong et al, 2012), thus the length of the dendritic arbor is critical for signal integration. Dendritic functional roles are also critical in the storage of long-term memory (Govindarajan et al, 2011).…”

Section: Dendritic Structure and Functionmentioning

confidence: 99%

Molecular mechanisms of dendrite morphogenesis

Arikkath¹

2012

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Dendrites are key integrators of synaptic information in neurons and play vital roles in neuronal plasticity. Hence, it is necessary that dendrite arborization is precisely controlled and coordinated with synaptic activity to ensure appropriate functional neural network integrity. In the past several years, it has become increasingly clear that several cell intrinsic and extrinsic mechanisms contribute to dendritic arborization. In this review, we will discuss some of the molecular mechanisms that regulate dendrite morphogenesis, particularly in cortical and hippocampal pyramidal neurons and some of the implications of aberrant dendritic morphology for human disease. Finally, we will discuss the current challenges and future directions in the field.

show abstract

“…Cultures were fixed at 14 DIV with 4% (vol/vol) formaldehyde and stained as described previously (49). Primary antibodies and dilution used: chicken anti-MAP (1:10,000; Abcam), guinea pig anti-vGlut1 (1:5,000; Millipore), and rabbit anti-synaptotagmin-1 (1:2,000; W855; a gift from T. C. Sudhof, Stanford University).…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation of synaptotagmin-1 controls a post-priming step in PKC-dependent presynaptic plasticity

Jong

Meijer

Saarloos

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Presynaptic activation of the diacylglycerol (DAG)/protein kinase C (PKC) pathway is a central event in short-term synaptic plasticity. Two substrates, Munc13-1 and Munc18-1, are essential for DAGinduced potentiation of vesicle priming, but the role of most presynaptic PKC substrates is not understood. Here, we show that a mutation in synaptotagmin-1 (Syt1 T112A ), which prevents its PKCdependent phosphorylation, abolishes DAG-induced potentiation of synaptic transmission in hippocampal neurons. This mutant also reduces potentiation of spontaneous release, but only if alternative Ca 2+ sensors, Doc2A/B proteins, are absent. However, unlike mutations in Munc13-1 or Munc18-1 that prevent DAG-induced potentiation, the synaptotagmin-1 mutation does not affect pairedpulse facilitation. Furthermore, experiments to probe vesicle priming (recovery after train stimulation and dual application of hypertonic solutions) also reveal no abnormalities. Expression of synaptotagmin-2, which lacks a seven amino acid sequence that contains the phosphorylation site in synaptotagmin-1, or a synaptotagmin-1 variant with these seven residues removed (Syt1 Δ109-116 ), supports normal DAG-induced potentiation. These data suggest that this seven residue sequence in synaptotagmin-1 situated in the linker between the transmembrane and C2A domains is inhibitory in the unphosphorylated state and becomes permissive of potentiation upon phosphorylation. We conclude that synaptotagmin-1 phosphorylation is an essential step in PKC-dependent potentiation of synaptic transmission, acting downstream of the two other essential DAG/PKC substrates, Munc13-1 and Munc18-1.P resynaptic strength changes rapidly during repetitive stimulation [short-term plasticity (STP)] and activation of intracellular signal transduction pathways (1, 2). The diacylglycerol (DAG)/protein kinase C (PKC) cascade is one of the most potent pathways at the presynaptic terminal. Its activation leads to 50-100% potentiation of spontaneous and action potential (AP)-evoked release (3-5), and is critical for multiple forms of presynaptic plasticity (6-8). DAG directly activates the vesicle priming factor Munc13-1 (9, 10) and indirectly activates downstream effectors via PKC. Activation of both Munc13-1 and PKC is essential for this pathway to operate (Fig. 1A) (8, 11). We previously identified Munc18-1 as an essential PKC substrate, because a nonphosphorylatable Munc18-1 mutant completely inhibits PKC-dependent STP (8, 12). Importantly, a phosphomimetic mutation of Munc18-1 cannot fully bypass the requirement for PKC activation, indicating that other PKC substrates must contribute to this form of plasticity (8). These substrates have not been identified to date.Among other presynaptic PKC substrates is synaptotagmin-1 (Syt1, ref. 13). Syt1 is the vesicular Ca 2+ sensor that mediates fast AP-evoked release in the hippocampus (14) and drives a large fraction of spontaneous release (15). In the latter case, Syt1 competes with alternative sensors, in particular Doc2s, for SNARE binding ...

show abstract

Dendritic position is a major determinant of presynaptic strength

Abstract: Positional information, independent of neuronal activity, regulates presynaptic strength, with the strongest presynaptic terminals closest to the soma.

Cited by 24 publications

References 56 publications

Common strength and localization of spontaneous and evoked synaptic vesicle release sites

Common strength and localization of spontaneous and evoked synaptic vesicle release sites

Molecular mechanisms of dendrite morphogenesis

Phosphorylation of synaptotagmin-1 controls a post-priming step in PKC-dependent presynaptic plasticity

Contact Info

Product

Resources

About