Presynaptic DLG regulates synaptic function through the localization of voltage-activated Ca2+ Channels

César Astorga; Ramón A. Jorquera; Mauricio Ramírez; Andrés Kohler; Estefanía López; Ricardo Delgado; Alex Córdova; Patricio Olguín; Jimena Sierralta

doi:10.1038/srep32132

Endogenous tagging reveals differential regulation of Ca2+ channels at single AZs during presynaptic homeostatic potentiation and depression

10.1101/240051 ◽

2017 ◽

Cited By ~ 4

Author(s):

Scott J. Gratz ◽

Pragya Goel ◽

Joseph J. Bruckner ◽

Roberto X. Hernandez ◽

Karam Khateeb ◽

...

Keyword(s):

Information Flow ◽

Neurotransmitter Release ◽

Synaptic Strength ◽

Live Imaging ◽

Differential Regulation ◽

Synaptic Function ◽

Homeostatic Plasticity ◽

Multiple Forms ◽

Active Zones ◽

Ca2 Channels

AbstractNeurons communicate through Ca2+-dependent neurotransmitter release at presynaptic active zones (AZs). Neurotransmitter release properties play a key role in defining information flow in circuits and are tuned during multiple forms of plasticity. Despite their central role in determining neurotransmitter release properties, little is known about how Ca2+ channel levels are modulated to calibrate synaptic function. We used CRISPR to tag the Drosophila CaV2 Ca2+ channel Cacophony (Cac) and investigated the regulation of endogenous Ca2+ channels during homeostatic plasticity in males in which all endogenous Cac channels are tagged. We found that heterogeneously distributed Cac is highly predictive of neurotransmitter release probability at individual AZs and differentially regulated during opposing forms of presynaptic homeostatic plasticity. Specifically, Cac levels at AZ are increased during chronic and acute presynaptic homeostatic potentiation (PHP), and live imaging during acute expression of PHP reveals proportional Ca2+ channel accumulation across heterogeneous AZs. In contrast, endogenous Cac levels do not change during presynaptic homeostatic depression (PHD), implying that the reported reduction in Ca2+ influx during PHD is achieved through functional adaptions to pre-existing Ca2+ channels. Thus, distinct mechanisms bi-directionally modulate presynaptic Ca2+ levels to maintain stable synaptic strength in response to diverse challenges, with Ca2+ channel abundance providing a rapidly tunable substrate for potentiating neurotransmitter release over both acute and chronic timescales.

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Neurological phenotype and synaptic function in mice lacking the CaV1.3 α subunit of neuronal L-type voltage-dependent Ca2+ channels

Neuroscience ◽

10.1016/s0306-4522(03)00329-4 ◽

2003 ◽

Vol 120 (2) ◽

pp. 435-442 ◽

Cited By ~ 45

Author(s):

N.C Clark ◽

N Nagano ◽

F.M Kuenzi ◽

W Jarolimek ◽

I Huber ◽

...

Keyword(s):

Synaptic Function ◽

Α Subunit ◽

Voltage Dependent ◽

Neurological Phenotype ◽

Ca2 Channels

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Postsynaptic neuronal geometry and synaptic effectiveness

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100127840 ◽

1987 ◽

Vol 45 ◽

pp. 690-697

Author(s):

C.J. Wilson

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Synaptic Function ◽

Postsynaptic Neuron ◽

Synaptic Inputs ◽

Partial Analysis ◽

Postsynaptic Cell ◽

Neuronal Geometry ◽

The Relationship ◽

Complex Scale

Most central nervous system neurons receive synaptic input from hundreds or thousands of other neurons, and the computational function of such neurons results from the interactions of inputs on a large and complex scale. In most situations that have yielded to a partial analysis, the synaptic inputs to a neuron are not alike in function, but rather belong to distinct categories that differ qualitatively in the nature of their effect on the postsynaptic cell, and quantitatively in the strength of their influence. Many factors have been demonstrated to contribute to synaptic function, but one of the simplest and best known of these is the geometry of the postsynaptic neuron. The fundamental nature of the relationship between neuronal shape and synaptic effectiveness was established on theoretical grounds prior to its experimental verification.

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Three-dimensional structure of dendritic spines, neuronal specializations that impart both stability and flexibility to synaptic function

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100146308 ◽

1993 ◽

Vol 51 ◽

pp. 92-93

Author(s):

Kristen M. Harris

Keyword(s):

Dendritic Spines ◽

Three Dimensional ◽

Synaptic Function ◽

Dimensional Structure ◽

Excitatory Synapses ◽

Concept Of Function ◽

Section Electron ◽

High Quality Information ◽

The Central Nervous System ◽

Mathematical Analyses

Dendritic spines are the tiny protrusions that stud the surface of many neurons and they are the location of over 90% of all excitatory synapses that occur in the central nervous system. Their small size and variable shapes has in large part made detailed study of their structure refractory to conventional light microscopy and single section electron microscopy (EM). Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic conditions. Since the seminal mathematical analyses of D’Arcy Thompson, the power of establishing quantitatively key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines highly precise determinations of structure and its variation are proving themselves as the kingpin for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has produced a flurry of new considerations of their role in synaptic transmission.

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