Actin-Dependent Regulation of Neurotransmitter Release at Central Synapses

Morales, Miguel; Colicos, Michael A.; Goda, Yukiko

doi:10.1016/s0896-6273(00)00064-7

Cited by 275 publications

(283 citation statements)

References 45 publications

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“…These values are not different from those of control experiments, which suggests that latrunculin has no augmenting effects on quantal release probability. Such an effect had been described in hippocampal cultures (Morales et al, 2001). On the other hand, during second pulses, EPSCs were much smaller; this can be seen by comparing Figures 1 A and 4 A (arrows).…”

Section: Nem and Staurosporine Do Not Affect Recruitment Of Releasablmentioning

confidence: 67%

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

2003

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Depletion and replenishment of pools of synaptic vesicles are important determinants of short-term synaptic plasticity, but the underlying molecular mechanisms are not yet clear. As a first step toward understanding the process of vesicle recruitment, we have applied various specific agents directly to the presynaptic terminal of the calyx of Held synapse. Here we show that the nonhydrolyzable ATP analog ATP-␥S retards the recovery from vesicle pool depletion, as does latrunculin A. Phalloidin has no effects on recovery, suggesting that dynamic actin reorganization is not necessary. Unexpectedly, neither N-ethylmaleimide nor staurosporine affected the recovery, calling into question the role of N-ethylmaleimide-sensitive factor and protein kinases. The results suggest that intact actin polymerization is involved in vesicle recruitment.

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Section: Nem and Staurosporine Do Not Affect Recruitment Of Releasablmentioning

confidence: 67%

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

2003

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“…Several studies have shown that synaptic vesicles are associated with a variety of cytoskeletal and motor proteins (Dresbach et al 2001;Evans et al 1998;Miyamoto 1995;Morales et al 2000;Prekeris and Terrian 1997;Ryan 1999). The synapsin family of phosphoproteins, which tethers vesicles to actin filaments, has been studied the most (Benfenati et al 1989;Greengard et al 1993;Pieribone et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Bui

Glavinović

2012

Cogn Neurodyn

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Short-term synaptic depression mainly reflects the depletion of the readily releasable pool (RRP) of quanta. Its dynamics, and especially the replenishment rate of the RRP, are still not well characterized in spite of decades of investigation. Main reason is that the vesicular storage and release system is treated as time-independent. If it is time-dependent all parameters thus estimated become problematic. Indeed the reports about how prolonged stimulation affects the dynamics are contradictory. To study this, we used patterned stimulation on the Schaeffer collateral fiber pathway and model-fitting of the excitatory post-synaptic currents (EPSC) recorded from CA1 neurons in rat hippocampal slices. The parameters of a vesicular storage and release model with two pools were estimated by minimizing the squared difference between the ESPC amplitudes and simulated model output. This yields the 'basic' parameters (release coupling, replenishment coupling and RRP size) that underlie the 'derived' and commonly used parameters (fractional release and replenishment rate). The fractional release increases when [Ca ?? ] o is raised, whereas the replenishment rate is [Ca ?? ] o independent. Fractional release rises because release coupling increases, and the RRP becomes less able to contain quanta. During prolonged stimulation, the fractional release remains generally unaltered, whereas the replenishment rate decreases down to *10 % of its initial value with a decay time of *15 s, and this decrease in the replenishment rate significantly contributes to synaptic depression. In conclusion, the fractional release is [Ca ?? ] odependent and stimulation-independent, whereas the replenishment rate is [Ca ?? ] o -independent and stimulation-dependent.

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“…Pharmacologic studies and the subsynaptic distribution of actin filaments also suggest a role for actin in neurotransmitter release (13,14). Actin depolymerizing proteins of the actin depolymerizing factor (ADF)/cofilin family are essential regulators of actin dynamics (15).…”

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confidence: 99%

Attention-Deficit/Hyperactivity Disorder–like Phenotype in a Mouse Model with Impaired Actin Dynamics

Zimmermann

Jene

Wolf

et al. 2015

Biological Psychiatry

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BACKGROUND: Actin depolymerizing proteins of the actin depolymerizing factor (ADF)/cofilin family are essential for actin dynamics, which is critical for synaptic function. Two ADF/cofilin family members, ADF and n-cofilin, are highly abundant in the brain, where they are present in excitatory synapses. Previous studies demonstrated the relevance of n-cofilin for postsynaptic plasticity, associative learning, and anxiety. These studies also suggested overlapping functions for ADF and n-cofilin. METHODS: We performed pharmacobehavioral, electrophysiologic, and electron microscopic studies on ADF and n-cofilin single mutants and double mutants (named ACC mice) to characterize the importance of ADF/cofilin activity for synapse physiology and mouse behavior. RESULTS: The ACC mice, but not single mutants, exhibited hyperlocomotion, impulsivity, and impaired working memory. Hyperlocomotion and impulsive behavior were reversed by methylphenidate, a psychostimulant commonly used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Also, ACC mice displayed a disturbed morphology of striatal excitatory synapses, accompanied by strongly increased glutamate release. Blockade of dopamine or glutamate transmission resulted in normal locomotion. CONCLUSIONS: Our study reveals that ADHD can result from a disturbed balance between excitation and inhibition in striatal circuits, providing novel insights into the mechanisms underlying this neurobehavioral disorder. Our results link actin dynamics to ADHD, suggesting that mutations in actin regulatory proteins may contribute to the etiology of ADHD in humans.

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Actin-Dependent Regulation of Neurotransmitter Release at Central Synapses

Cited by 275 publications

References 45 publications

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

Involvement of Actin Polymerization in Vesicle Recruitment at the Calyx of Held Synapse

Synaptic activity slows vesicular replenishment at excitatory synapses of rat hippocampus

Attention-Deficit/Hyperactivity Disorder–like Phenotype in a Mouse Model with Impaired Actin Dynamics

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