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Home / Once Neurotransmitters Are Released, They Do Not Remain in the Synapse. What Happens to Them?

Once Neurotransmitters Are Released, They Do Not Remain in the Synapse. What Happens to Them?

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  • Wiley-Blackwell Online Open
  • PMC5813191

J Neurosci Res. 2018 Mar; 96(3): 354–359.

The role of spontaneous neurotransmission in synapse and excursion evolution

Laura C. Andreae

1 Centre for Developmental Neurobiology, Male monarch's College London, New Hunt's Business firm, 4th Floor, Guy's Infirmary Campus, London, SE1 1UL, UK,

2 MRC Middle for Neurodevelopmental Disorders, King'southward Higher London, New Hunt'southward Business firm, 4th Floor, Guy's Hospital Campus, London, SE1 1UL, UK,

3 FENS‐Kavli Network of Excellence, Europe‐wide,

Juan Burrone

1 Center for Developmental Neurobiology, King's College London, New Hunt'due south House, quaternary Floor, Guy's Hospital Campus, London, SE1 1UL, UK,

2 MRC Center for Neurodevelopmental Disorders, Male monarch's College London, New Hunt's Business firm, quaternary Floor, Guy'south Infirmary Campus, London, SE1 1UL, UK,

Received 2017 May 2; Revised 2017 Aug 18; Accepted 2017 Aug 21.

Abstruse

In the by, the spontaneous release of neurotransmitter from presynaptic terminals has been thought of equally a side issue of evoked release, with lilliputian functional significance. As our understanding of the process of spontaneous release has increased over fourth dimension, this notion has gradually inverse. In this review, we focus on the importance of this grade of release during neuronal development, a time of extreme levels of plasticity that includes the growth of dendrites and axons as well equally the formation of new synaptic contacts. This flow also encompasses high levels of neurotransmitter release from growing axons, and recent studies accept establish that spontaneous transmitter release plays an important role in shaping neuronal morphology likewise as modulating the properties of newly forming synaptic contacts in the encephalon. Here, we bring together the latest findings across unlike species to debate that the spontaneous release of neurotransmitter is an important histrion in the wiring of the encephalon during evolution.

Keywords: spontaneous, miniature, neurotransmitter release, synapse formation, development, dendritic arbor

Advice betwixt neurons largely happens at the chemical synapse, where neurotransmitters are released from presynaptic vesicles, cantankerous the narrow synaptic fissure, and activate receptors on the postsynaptic neuron. The trigger for neurotransmitter release is the firing of an action potential in the presynaptic neuron; when depolarization invades the presynaptic final, voltage‐gated calcium channels open up, and the rise in intracellular calcium at the last (or bouton) leads to fusion of vesicles with the plasma membrane and exocytosis of their contents. Notwithstanding, in addition to this activeness‐dependent (or evoked) transmitter release, synaptic vesicles tin can spontaneously fuse and release a single packet (or quantum) of neurotransmitter. This spontaneous vesicular release can exist detected postsynaptically every bit a miniature postsynaptic current. The discovery of this form of release by Bernard Katz in 1952 (Fatt & Katz, 1952) was key to our understanding of the quantal nature of neurotransmission; however, spontaneous release itself was often regarded as 'noise' in the system, having no intrinsic function. Increasingly this view is now beingness challenged, and indeed contempo work has demonstrated that the antidepressant actions of ketamine may act via effects on spontaneous neurotransmission, with important implications for developing new treatments for depression (Autry et al., 2011; Kavalali & Monteggia, 2015). In this review, we will focus on the role of spontaneous transmission during neuronal development.

In order to form a synapse, the presynaptic axon must make contact with the postsynaptic dendrite, following which, pre‐ and post‐synaptic machinery needs to exist assembled at this site. As one might wait, this requires a host of guidance cues that aid the axon in finding its target and a variety of prison cell‐adhesion molecules that promote synapse germination (Sanes & Yamagata, 2009; Shen & Scheiffele, 2010). At the same time, axonal and dendritic arborizations progressively enlarge and get more than complex, allowing more than synapses to form and circuits to be congenital. These processes are clearly linked, and indeed may depend, to some extent, on each other (Vaughn, 1989). Traditionally, the role of neuronal activity has been seen every bit i of refinement, such that in one case the basic structure of connections is established, the less agile ones tin be pruned away, often via competitive mechanisms (Huberman, Feller, & Chapman, 2008; Katz & Shatz, 1996; LeVay, Wiesel, Hubel, 1980; Sanes & Lichtman, 1999). More recently, it is condign articulate that activeness may also be important for synapse and circuit germination per se (Andreae & Burrone, 2014; Choi et al., 2014; Okawa et al., 2014; Sabo, Gomes, & McAllister, 2006), although this remains a controversial field (Sigler et al., 2017). Indeed, it seems that specifically spontaneous neurotransmission may regulate various aspects of this process.

1. NEUROTRANSMITTER RELEASE DURING DEVELOPMENT

It has long been known that immature neurons tin can release neurotransmitter from their axons before making contact with a postsynaptic neuron. Studies in cultured Xenopus spinal neurons constitute that both growth cones (Young & Poo, 1983) and sites along the axon (Dai & Peng, 1996; Zakharenko, Chang, O'Donoghue, & Popov, 1999) spontaneously released the neurotransmitter acetylcholine. Similarly, synaptic vesicles from both chick peripheral neurons (Hume, Role, & Fischbach, 1983; Tojima et al., 2007) and rodent central nervous organisation (CNS) neurons were also found to be capable of cycling before synapse formation (Kraszewski et al., 1995; Matteoli, Takei, Perin, Sudhof, & De Camilli, 1992; Sabo et al., 2006). While in some preparations, activity dependent release from these young axons has been conspicuously demonstrated, such as Xenopus spinal neurons (Zakharenko et al., 1999), at that place were early indications that evoked release in mammalian CNS neurons may be developmentally regulated. Using the styryl dye FM2‐10 to label cycling vesicles, Mozhayeva et al. (2002) found that levels of evoked release in cultured rat hippocampal neurons progressively increased during development, and at the primeval stage studied (5DIV) most no response to activity was seen.

Merely what of spontaneous neurotransmitter release in developing neurons? Spontaneous release had traditionally been studied by using whole‐cell patch clamp electrophysiology to record miniature postsynaptic currents (or 'minis') from the postsynaptic prison cell, and using this arroyo, a progressive increase in the frequency of these currents during development had been observed (Desai, Cudmore, Nelson, & Turrigiano, 2002; Mozhayeva, Sara, Liu, & Kavalali, 2002). However, this presumably reflects the known increase in synaptic connections, and restricts analysis to afterward synapse formation. To examine levels of spontaneous release directly at individual boutons, fluorescent reporters of vesicle exocytosis take been used to integrate the total number of release events over long periods of time, in the absenteeism of whatever action. One such reporter of presynaptic vesicle exocytosis, biosyn (a biotinylated VAMP2), is well suited to independently written report both evoked and spontaneous vesicle cycling within the same presynaptic bouton, with different colors (Fredj & Burrone, 2009). Using this tool in cultured rat hippocampal neurons evoked release was found to increase with development in a manner similar to that previously observed (Mozhayeva et al., 2002), only spontaneous vesicle cycling was constitute to occur at exceptionally high levels in immature neurons, which progressively decreased with maturation (Andreae, Fredj, & Burrone, 2012). Farther analysis, including the additional utilise of the pH‐sensitive reporter synaptopHluorin, a transient reporter of vesicle exocytosis and endocytosis, indicated that at early stages before synapse formation (4‐5 days in vitro, DIV) evoked release was completely absent, despite robust calcium responses to depolarization. In agreement with findings in developed neurons, spontaneously cycling vesicles throughout development were found to derive from a vesicle pool which was independent of the vesicle puddle cycling in response to action, even though they coexisted in the aforementioned presynaptic bouton. Although circumstantial, the fact that developing mammalian CNS neurons exhibit very high levels of spontaneous synaptic vesicle cycling, in the absence of evoked release early, suggests that spontaneous release has an important role to play during development.

2. SPONTANEOUS RELEASE REGULATES PRESYNAPTIC MATURATION

Show implicating spontaneous release in the maturation of presynaptic boutons comes from studies of the Drosophila neuromuscular junction (NMJ). An early clue emerged from piece of work on Drosophila mutant flies that were nada for the SNARE complex binding poly peptide, complexin. These mutant flies exhibited an increase in spontaneous vesicle fusion at the NMJ, equally well as an increased number of presynaptic boutons in the innervating motor neurons (Huntwork & Littleton, 2007). Although at this stage there was no evidence that ane led to the other, in 2015 the Littleton group revisited this event when they noticed that a number of different mutations that all resulted in increased spontaneous release at the NMJ (as identified past increased frequency of minis) were too all associated with increased numbers of presynaptic boutons. When they quantified the relative levels of these ii features in the different mutants, they found that there was a directly correlation betwixt the level of increase in spontaneous release and the number of boutons (Cho et al., 2015). Detailed label of this miracle led them to identify postsynaptic syt4 and presynaptic BMP release as critical for the increase in presynaptic growth.

In line with these findings and lending farther back up to an instructive role for spontaneous release during development, another cardinal study in the Drosophila NMJ carefully dissected out the office of spontaneous neurotransmission on the maturation of synaptic boutons themselves (Choi et al., 2014; Figure ​ 1). The study found that specifically blocking spontaneous release resulted in an increased proportion of small presynaptic boutons and a generally reduced motor neuron final surface area, which could non be rescued past increasing evoked release (Figure ​ aneB). The effect on boutons was due to a slowing downwardly of bouton enlargement. When they increased spontaneous release by using the complexin mutant, they found the opposite upshot on bouton maturation. Interestingly, these structural synaptic changes were dependent on presynaptic Trio (a Global environment facility) and Rac1 acting downstream of spontaneous release and directly modulating the actin cytoskeleton (Choi et al., 2014). Although it is withal unclear how synapses distinguish betwixt evoked and spontaneous release to modulate distinct pathways, studies in hippocampal neurons have shown each mode of release tin can activate distinct subsets of postsynaptic glutamate (NMDA and AMPA) receptors (Atasoy et al., 2008; Reese & Kavalali, 2016; Sara, Bal, Adachi, Monteggia, & Kavalali, 2011). Similar notions have also recently been reported in Drosophila synapses (Melom, Akbergenova, Gavornik, & Littleton, 2013; Peled, Newman, & Isacoff, 2014), raising the intriguing possibility that spontaneous and evoked release actuate distinct postsynaptic molecular cascades by acting on spatially segregated receptors (Kavalali, 2015).

An external file that holds a picture, illustration, etc. Object name is JNR-96-354-g001.jpg

Spontaneous release is important for axonal and dendritic development. A. Neurons undergo both spontaneous and evoked release during evolution (traces on the left) and tools can be used to selectively interfere with spontaneous release (traces on the correct). B. At the Drosophila neuromuscular junction (NMJ), interfering with spontaneous neurotransmitter release, but not evoked release, during the period of synaptogenesis causes the germination of aberrant presynaptic terminal boutons. These are mainly observed every bit an increased number of small-scale presynaptic boutons and a subtract in overall synaptic last expanse. C. In mammalian hippocampal neurons, where release from developing axons occurs predominantly in a spontaneous way and activates dendritic NMDA receptors (yellow event), interfering with NMDAR activity driven past spontaneous release results in less complex dendritic arbors

three. ROLE FOR SPONTANEOUS NEUROTRANSMISSION ON POSTSYNAPTIC DEVELOPMENT AND DENDRITIC ARBOR FORMATION

Evidence that spontaneous neurotransmitter release might be playing a part in the dendritic growth of excitatory neurons has been around since the 1990s, even though information technology was often non straight studied at the fourth dimension. One of the offset clues came from experiments examining the furnishings of the neurotrophin, brain‐derived neurotrophic gene (BDNF), on the growth of layer 4 cortical pyramidal neurons in cultured slices of ferret visual cortex (McAllister, Katz, & Lo, 1996). These are excitatory neurons with both an apical and basal dendritic arbor, and handling with BDNF resulted in increased growth of both arbors. Even so, when the authors attempted to interfere with the furnishings of BDNF by blocking activity, some interesting distinctions emerged. In the apical dendrites, blocking action potential firing (with tetrodotoxin [TTX]), and hence evoked transmitter release, or glutamate receptors (with either CNQX to antagonise AMPA receptors, or APV to antagonise NMDA receptors) each reduced the effects of BDNF on growth. Even so, in basal dendrites, TTX alone had a minimal issue whereas glutamate receptor antagonists prevented the BDNF‐induced growth, suggesting that spontaneous (merely non evoked) release of glutamate is needed for this BDNF plasticity. More directly, an in vivo report of tectal neuron development in Xenopus plant that NMDA receptor occludent led to decreased dendritic growth, a reduced charge per unit of new branch additions and impaired branch extension, while blocking evoked transmitter release with TTX had no event (Rajan, Witte, & Cline, 1999), again implicating spontaneous release.

Excitatory, glutamatergic synapses exhibit a singled-out morphology at the postsynaptic side in the form of dendritic protrusions, or spines. A key study specifically examining the role of spontaneous transmission in rodent hippocampal neurons plant that it was disquisitional for the maintenance of dendritic spines, especially in the context of deafferentation of spine inputs (McKinney, Capogna, Durr, Gahwiler, & Thompson, 1999). Although this was less of a truthful developmental effect, information technology did firmly point the finger at spontaneous glutamate release in the regulation of spine density, which could have obvious implications earlier in development. Further evidence that spontaneous transmission is important for excitatory synapse stability in mature neurons came from the sit-in that NMDA receptor dependent miniature currents help to keep homeostatic synaptic scaling in check during occludent of neuronal firing by restricting synthesis of certain AMPA receptor subunits (Sutton et al., 2006; see accompanying review on this topic in this event). Interestingly, work at the Drosophila NMJ utilizing mutants of presynaptic function also suggested that the spontaneous release of glutamate could control postsynaptic glutamate receptor clustering (Saitoe, Schwarz, Umbach, Gundersen, & Kidokoro, 2001), which in mammals is strongly correlated with spine size (Matsuzaki et al., 2001; Zito, Scheuss, Knott, Colina, & Svoboda, 2009), although these findings are controversial (Featherstone, Rushton, & Broadie, 2002), possibly due to variations in the extent to which spontaneous release is impaired in dissimilar mutant flies (Featherstone & Broadie, 2002; Saitoe et al., 2002).

A recent study delved further into a possible role for spontaneous release early in evolution, given the very high levels of spontaneous vesicle cycling seen in more than immature rodent neurons (Andreae et al., 2012). This found that spontaneously released glutamate from immature axons could signal to distant NMDA receptors on developing dendrites. To dissect out the specific role of spontaneous release the authors were able to take reward of a culture arrangement where neuronal evolution was relatively synchronized, pregnant that at specified early stages only spontaneous release was present, while at later stages evoked release was predominant. Blocking NMDA receptors early, during a period where neurotransmitter release was exclusively spontaneous, resulted in a dramatic reduction in dendritic arbor complexity, while neither TTX (to block neuronal firing) nor NMDA blockade (at later stages) had whatsoever effect. Interfering with spontaneously released glutamate reduced dendritic complexity and as well resulted in straighter dendrites with more symmetrical arbors (Figure ​ oneC). This suggested that the released glutamate might be acting as a kind of dendritic branch guidance, or growth promoting, cue. Indeed, several instances of dendritic filopodia reaching out and targeting axonal boutons were observed, at sites where spontaneously cycling vesicles had been specifically labelled (Andreae & Burrone, 2015).

iv. CONCLUSIONS AND CONTROVERSIES

In summary, there is at present a meaning body of evidence that spontaneous neurotransmitter release plays an important role in the evolution of neuronal connections and dendritic arbors. Understanding how synapses and circuits develop is increasingly relevant, equally it becomes articulate that many neurodevelopmental disorders, such as autism or intellectual disability, are likely to involve disruptions to these processes. Wiring the brain correctly early in development may be critical for allowing subsequent circuitous learning to have place. Indeed, a recent computational study that modelled the development of unlike forms of release found that early on spontaneous release (with lower levels of evoked release) resulted in a homogenization of synaptic weights initially, which was critical to maintain an advisable dynamic range of weights and might 'prepare' circuits for learning (Martens, Celikel, & Tiesinga, 2015). But many questions remain. Most vertebrate studies have been carried out using in vitro systems, and it will exist of import to validate these findings in vivo.

As well, the extent to which neurotransmitter release in general drives synaptic and neuronal development remains a controversial question. Indeed, a recent study examining hippocampal CA1 subfield pyramidal neurons from mice that lacked both spontaneous and evoked release (due to the absence of key SNARE proteins) establish no profound changes (Sigler et al., 2017) while another report which used tetanus toxin to block release describe the loss of almost half of excitatory synapses on to the same neuronal type, with impaired dendritic arborizations (Sando et al., 2017). There is a great deal of evidence from the literature that using different approaches to modulating activity tin can result in different effects on synapse germination (Andreae & Burrone, 2014), and indeed, it is unclear how much of an impact tetanus toxin has on early on spontaneous release (Andreae & Burrone, 2015; Choi et al., 2014; Shin et al., 2012; Verderio et al., 1999). Interestingly, the second study found very different effects on neurons in the CA3 region of the hippocampus, suggesting that even inside the aforementioned microcircuit, the role of activity can exist varied. This miracle has been elegantly described in the mouse retina where selective silencing of specific neurons had completely different impacts on synapse formation onto individual neuronal subtypes (Dunn & Wong, 2012; Kerschensteiner, Morgan, Parker, Lewis, & Wong, 2009; Morgan, Soto, Wong, & Kerschensteiner, 2011; Soto et al., 2012). Similarly, different interneuron subtypes in the developing mouse cortex are differentially affected past modifying activity (De Marco Garcia, Karayannis, & Fishell, 2011), which was dependent on input source acting through different NMDA subtypes (De Marco Garcia, Priya, Tuncdemir, Fishell, & Karayannis, 2015). In addition, competitive processes that arise from differences in neurotransmitter release betwixt neurons may take a meaning bear upon on connectivity, meaning that intendance is needed in interpreting studies that focus on the complete removal of release from all neurons. Approaches where release is selectively removed from a subset of neurons volition allow a more than in depth investigation equally to how release affects connectivity.

Nigh all the work investigating the office of spontaneous neurotransmission has focused on the development of glutamatergic synapses, but might similar mechanisms be employed at inhibitory, GABAergic synapses? GABAergic interneurons have a very different developmental program in terms of regional origin, transcriptional regulators and migration patterns from excitatory neurons, and mature GABAergic synapses often testify much higher levels of spontaneous release, but whether this is seen during evolution and the role it might play is unknown. The nervous system is extraordinarily diverse, not only in terms of neuronal cell types or morphology, just at multiple levels including functional patterns of behaviour, plasticity rules and mechanisms, and circuit structure and part. How dissimilar types of neurotransmitter release regulate the germination of unlike synaptic connections and circuits will be a critical question for the future.

Writer CONTRIBUTIONS

All authors had full access to all the data in the study and take responsibility for the integrity of the information and the accuracy of the data analysis. Conceptualization, Methodology, Investigation, Formal Analysis, Resources, Visualization, Supervision, Funding Acquisition, Writing, Review & Editing: LCA and JB.

ACKNOWLEDGEMENTS

This piece of work was supported past a BBSRC and NARSAD Immature Investigator Accolade to LCA, and a Wellcome Trust Investigator Accolade, an ERC starter grant, and an EU FP7 Desire project grant to JB.

Notes

Andreae LC, Burrone J. The role of spontaneous neurotransmission in synapse and circuit development. J Neuro Res. 2018;96:354–359. https://doi.org/10.1002/jnr.24154 [PMC free article] [PubMed] [Google Scholar]

Funding information This work was supported by a BBSRC and NARSAD Young Investigator Honour (to LCA) and a Wellcome Trust Investigator Award, an ERC starter grant, and an Eu FP7 Desire project grant, (to JB).

Significance This review discusses the latest findings implicating spontaneous neurotransmitter release in the formation and maturation of brain circuits. Specifically, we talk over how dendritic morphology and the maturation of synaptic compartments are modulated during development. These findings non simply describe a novel part played by spontaneous release in the encephalon, but besides highlight its importance during the period of synapse and circuit formation.

Contributor Data

Laura C. Andreae, ku.ca.lck@eaerdna.arual.

Juan Burrone, ku.ca.lck@enorrub.nauj.

REFERENCES

  • Andreae, Fifty. C. , & Burrone, J. (2014). The part of neuronal activity and transmitter release on synapse formation. Current Opinion in Neurobiology, 27, 47‐52. [PMC costless article] [PubMed] [Google Scholar]
  • Andreae, L. C. , & Burrone, J. (2015). Spontaneous neurotransmitter release shapes dendritic arbors via long‐range activation of nmda receptors. Cell Reports, doi: x.1016/j.celrep.2015.01.032. [Epub alee of impress] [PMC gratis article] [PubMed] [Google Scholar]
  • Andreae, Fifty. C. , Fredj, Northward. B. , & Burrone, J. (2012). Independent vesicle pools underlie different modes of release during neuronal development. The Journal of Neuroscience, 32(five):1867‐1874. [PMC free article] [PubMed] [Google Scholar]
  • Atasoy, D. , Ertunc, M. , Moulder, G. 50. , Blackwell, J. , Chung, C. , Su, J. , & Kavalali, Due east. T. (2008). Spontaneous and evoked glutamate release activates two populations of NMDA receptors with express overlap. The Periodical of Neuroscience, 28(forty):10151‐10166. [PMC free article] [PubMed] [Google Scholar]
  • Autry, A. E. , Adachi, M. , Nosyreva, E. , Na, East. S. , Los, One thousand. F. , Cheng, P. F. , Kavalali, Due east. T. , & Monteggia, 50. M. (2011). NMDA receptor blockade at balance triggers rapid behavioural antidepressant responses. Nature, 475(7354):91‐95. [PMC free article] [PubMed] [Google Scholar]
  • Cho, R. Due west. , Buhl, L. Thou. , Volfson, D. , Tran, A. , Li, F. , Akbergenova, Y. , Littleton, J. T. (2015). Phosphorylation of complexin by pka regulates activity‐dependent spontaneous neurotransmitter release and structural synaptic plasticity. Neuron, 88(4):749‐761. [PMC complimentary article] [PubMed] [Google Scholar]
  • Choi, B. J. , Imlach, W. L. , Jiao, Westward. , Wolfram, V. , Wu, Y. , Grbic, M. , … McCabe, B. D. (2014). Miniature neurotransmission regulates Drosophila synaptic structural maturation. Neuron, 82(3):618‐634. [PMC gratis article] [PubMed] [Google Scholar]
  • Dai, Z. , & Peng, H. B. (1996). Dynamics of synaptic vesicles in cultured spinal cord neurons in relationship to synaptogenesis. Molecular and Cellular Neuroscience, vii(6):443‐452. [PubMed] [Google Scholar]
  • De Marco Garcia, N. Five. , Karayannis, T. , Fishell, One thousand. (2011). Neuronal action is required for the development of specific cortical interneuron subtypes. Nature, 472(7343):351‐355. [PMC free article] [PubMed] [Google Scholar]
  • De Marco Garcia, Due north. Five. , Priya, R. , Tuncdemir, S. N. , Fishell, G. , & Karayannis, T. (2015). Sensory inputs control the integration of neurogliaform interneurons into cortical circuits. Nature Neuroscience, eighteen(3):393‐401. [PMC free article] [PubMed] [Google Scholar]
  • Desai, N. S. , Cudmore, R. H. , Nelson, S. B. , & Turrigiano, K. K. (2002). Critical periods for experience‐dependent synaptic scaling in visual cortex. Nature Neuroscience, 5(8):783‐789. [PubMed] [Google Scholar]
  • Dunn, F. A. , & Wong, R. O. (2012). Diverse strategies engaged in establishing stereotypic wiring patterns among neurons sharing a mutual input at the visual system's offset synapse. The Journal of Neuroscience, 32(30):10306‐10317. [PMC free commodity] [PubMed] [Google Scholar]
  • Fatt, P. , & Katz, B. (1952). Spontaneous subthreshold activity at motor nerve endings. Journal of Physiology, 117(1):109‐128. [PMC free commodity] [PubMed] [Google Scholar]
  • Featherstone, D. , & Broadie, Yard. (2002). Response: meaningless minis? Trends in Neurosciences, 25(8):386‐387. [PubMed] [Google Scholar]
  • Featherstone, D. E. , Rushton, E. , & Broadie, K. (2002). Developmental regulation of glutamate receptor field size by nonvesicular glutamate release. Nature Neuroscience, five(two):141‐146. [PubMed] [Google Scholar]
  • Fredj, N. B. , & Burrone, J. (2009). A resting pool of vesicles is responsible for spontaneous vesicle fusion at the synapse. Nature Neuroscience, 12(6):751‐758. [PMC free commodity] [PubMed] [Google Scholar]
  • Huberman, A. D. , Feller, G. B. , & Chapman, B. (2008). Mechanisms underlying development of visual maps and receptive fields. Annual Review of Neuroscience, 31, 479‐509. [PMC gratis article] [PubMed] [Google Scholar]
  • Hume, R. I. , Role, 50. Westward. , & Fischbach, G. D. (1983). Acetylcholine release from growth cones detected with patches of acetylcholine receptor‐rich membranes. Nature, 305(5935):632‐634. [PubMed] [Google Scholar]
  • Huntwork, Southward. , & Littleton, J. T. (2007). A complexin fusion clench regulates spontaneous neurotransmitter release and synaptic growth. Nature Neuroscience, ten(10):1235‐1237. [PubMed] [Google Scholar]
  • Katz, L. C. , & Shatz, C. J. (1996). Synaptic activity and the construction of cortical circuits. Science 274(5290):1133‐1138. [PubMed] [Google Scholar]
  • Kavalali, E. T. (2015). The mechanisms and functions of spontaneous neurotransmitter release. Nature Reviews Neuroscience, 16(1):v‐16. [PubMed] [Google Scholar]
  • Kavalali, E. T. , & Monteggia, L. G. (2015). How does ketamine elicit a rapid antidepressant response? Electric current Opinion in Pharmacology, 20, 35‐39. [PMC free article] [PubMed] [Google Scholar]
  • Kerschensteiner, D. , Morgan, J. 50. , Parker, Eastward. D. , Lewis, R. M. , & Wong, R. O. (2009). Neurotransmission selectively regulates synapse formation in parallel circuits in vivo. Nature, 460(7258):1016‐1020. [PMC complimentary article] [PubMed] [Google Scholar]
  • Kraszewski, K. , Mundigl, O. , Daniell, L. , Verderio, C. , Matteoli, M. , & De Camilli, P. (1995). Synaptic vesicle dynamics in living cultured hippocampal neurons visualized with CY3‐conjugated antibodies directed against the lumenal domain of synaptotagmin. The Journal of Neuroscience, 15(half-dozen):4328‐4342. [PMC free article] [PubMed] [Google Scholar]
  • LeVay, S. , Wiesel, T. N. , Hubel, D. H. (1980). The evolution of ocular dominance columns in normal and visually deprived monkeys. The Journal of Comparative Neurology, 191(1):1‐51. [PubMed] [Google Scholar]
  • Martens, M. B. , Celikel, T. , & Tiesinga, P. H. (2015). A developmental switch for hebbian plasticity. PLoS Computational Biological science, 11(7):e1004386. [PMC free article] [PubMed] [Google Scholar]
  • Matsuzaki, K. , Ellis‐Davies, Thousand. C. , Nemoto, T. , Miyashita, Y. , Iino, M. , & Kasai, H. (2001). Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nature Neuroscience, 4(11):1086‐1092. [PMC free article] [PubMed] [Google Scholar]
  • Matteoli, Yard. , Takei, K. , Perin, G. Due south. , Sudhof, T. C. , De Camilli, P. (1992). Exo‐endocytotic recycling of synaptic vesicles in developing processes of cultured hippocampal neurons. The Journal of Cell Biology, 117(4):849‐861. [PMC free commodity] [PubMed] [Google Scholar]
  • McAllister, A. K. , Katz, L. C. , & Lo, D. C. (1996). Neurotrophin regulation of cortical dendritic growth requires activity. Neuron, 17(vi):1057‐1064. [PubMed] [Google Scholar]
  • McKinney, R. A. , Capogna, M. , Durr, R. , Gahwiler, B. H. , & Thompson, S. M. (1999). Miniature synaptic events maintain dendritic spines via AMPA receptor activation. Nature Neuroscience, 2(one):44‐49. [PubMed] [Google Scholar]
  • Melom, J. E. , Akbergenova, Y. , Gavornik, J. P. , & Littleton, J. T. (2013). Spontaneous and evoked release are independently regulated at individual active zones. The Periodical of Neuroscience, 33(44):17253‐17263. [PMC gratuitous article] [PubMed] [Google Scholar]
  • Morgan, J. L. , Soto, F. , Wong, R. O. , & Kerschensteiner, D. (2011). Development of jail cell blazon‐specific connectivity patterns of converging excitatory axons in the retina. Neuron, 71(six):1014‐1021. [PMC complimentary article] [PubMed] [Google Scholar]
  • Mozhayeva, M. G. , Sara, Y. , Liu, X. , & Kavalali, E. T. (2002). Development of vesicle pools during maturation of hippocampal synapses. The Journal of Neuroscience, 22(3):654‐665. [PMC free article] [PubMed] [Google Scholar]
  • Okawa, H. , Hoon, Grand. , Yoshimatsu, T. , Della Santina, L. , & Wong, R. O. (2014). Illuminating the multifaceted roles of neurotransmission in shaping neuronal circuitry. Neuron, 83(6):1303‐1318. [PMC gratis article] [PubMed] [Google Scholar]
  • Peled, E. S. , Newman, Z. 50. , & Isacoff, E. Y. (2014). Evoked and spontaneous transmission favored by distinct sets of synapses. Electric current Biology, 24(five):484‐493. [PMC gratis article] [PubMed] [Google Scholar]
  • Rajan, I. , Witte, S. , & Cline, H. T. (1999). NMDA receptor action stabilizes presynaptic retinotectal axons and postsynaptic optic tectal jail cell dendrites in vivo. Journal of Neurobiology, 38(iii):357‐368. [PubMed] [Google Scholar]
  • Reese, A. L. , & Kavalali, East. T. (2016). Single synapse evaluation of the postsynaptic NMDA receptors targeted by evoked and spontaneous neurotransmission. Elife, 5, e21170. doi: ten.7554/eLife.21170. [PMC complimentary article] [PubMed] [Google Scholar]
  • Sabo, S. L. , Gomes, R. A. , & McAllister, A. Grand. (2006). Formation of presynaptic terminals at predefined sites along axons. The Journal of Neuroscience, 26(42):10813‐10825. [PMC free commodity] [PubMed] [Google Scholar]
  • Saitoe, Thou. , Schwarz, T. L. , Umbach, J. A. , Gundersen, C. B. , & Kidokoro, Y. (2001). Absence of junctional glutamate receptor clusters in Drosophila mutants lacking spontaneous transmitter release. Science, 293(5529):514‐517. [PubMed] [Google Scholar]
  • Saitoe, M. , Schwarz, T. L. , Umbach, J. A. , Gundersen, C. B. , & Kidokoro, Y. (2002). Response: meaningless minis? Trends in Neurosciences 25(8):385‐386. [PubMed] [Google Scholar]
  • Sando, R. , Bushong, E. , Zhu, Y. , Huang, 1000. , Considine, C. , Phan, S. , … Maximov, A. (2017). Assembly of excitatory synapses in the absenteeism of glutamatergic neurotransmission. Neuron, 94(2):312‐321. [PMC free article] [PubMed] [Google Scholar]
  • Sanes, J. R. , & Lichtman, J. W. (1999). Development of the vertebrate neuromuscular junction. Annual Review of Neuroscience, 22, 389‐442. [PubMed] [Google Scholar]
  • Sanes, J. R. , & Yamagata, Thousand. (2009). Many paths to synaptic specificity. Annual Review of Cell and Developmental Biology, 25, 161‐195. [PubMed] [Google Scholar]
  • Sara, Y. , Bal, Thou. , Adachi, M. , Monteggia, L. K. , & Kavalali, Due east. T. (2011). Use‐dependent AMPA receptor block reveals segregation of spontaneous and evoked glutamatergic neurotransmission. The Periodical of Neuroscience, 31(xiv):5378‐5382. [PMC complimentary article] [PubMed] [Google Scholar]
  • Shen, K. , & Scheiffele, P. (2010). Genetics and cell biology of building specific synaptic connectivity. Annual Review of Neuroscience, 33, 473‐507. [PMC free article] [PubMed] [Google Scholar]
  • Shin, M. C. , Nonaka, G. , Wakita, Grand. , Yamaga, T. , Torii, Y. , Harakawa, T. , … Akaike, Due north. (2012). Effects of tetanus toxin on spontaneous and evoked transmitter release at inhibitory and excitatory synapses in the rat SDCN neurons. Toxicon, 59(3):385‐392. [PubMed] [Google Scholar]
  • Sigler, A. , Oh, W. C. , Imig, C. , Altas, B. , Kawabe, H. , Cooper, B. H. , … Brose, N. (2017). Formation and maintenance of functional spines in the absence of presynaptic glutamate release. Neuron, 94(2):304‐311. [PMC free article] [PubMed] [Google Scholar]
  • Soto, F. , Ma, 10. , Cecil, J. 50. , Vo, B. Q. , Culican, S. M. , & Kerschensteiner, D. (2012). Spontaneous activity promotes synapse formation in a cell‐type‐dependent manner in the developing retina. The Journal of Neuroscience, 32(16):5426‐5439. [PMC costless commodity] [PubMed] [Google Scholar]
  • Sutton, Yard. A. , Ito, H. T. , Cressy, P. , Kempf, C. , Woo, J. C. , & Schuman, Due east. M. (2006). Miniature neurotransmission stabilizes synaptic function via tonic suppression of local dendritic poly peptide synthesis. Prison cell, 125(4):785‐799. [PubMed] [Google Scholar]
  • Tojima, T. , Akiyama, H. , Itofusa, R. , Li, Y. , Katayama, H. , Miyawaki, A. , & Kamiguchi, H. (2007). Attractive axon guidance involves disproportionate membrane transport and exocytosis in the growth cone. Nature Neuroscience, 10(ane):58‐66. [PubMed] [Google Scholar]
  • Vaughn, J. E. (1989). Fine structure of synaptogenesis in the vertebrate primal nervous arrangement. Synapse, 3(3):255‐285. [PubMed] [Google Scholar]
  • Verderio, C. , Coco, S. , Bacci, A. , Rossetto, O. , De Camilli, P. , Montecucco, C. , & Matteoli, Thou. (1999). Tetanus toxin blocks the exocytosis of synaptic vesicles clustered at synapses merely not of synaptic vesicles in isolated axons. The Journal of Neuroscience, 19(16):6723‐6732. [PMC free article] [PubMed] [Google Scholar]
  • Immature, Southward. H. , & Poo, M. One thousand. (1983). Spontaneous release of transmitter from growth cones of embryonic neurones. Nature, 305(5935):634‐637. [PubMed] [Google Scholar]
  • Zakharenko, South. , Chang, Southward. , O'Donoghue, M. , & Popov, SV. (1999). Neurotransmitter secretion along growing nervus processes: comparison with synaptic vesicle exocytosis. The Journal of Cell Biology, 144(three):507‐518. [PMC free article] [PubMed] [Google Scholar]
  • Zito, K. , Scheuss, 5. , Knott, 1000. , Colina, T. , & Svoboda, K. (2009). Rapid functional maturation of nascent dendritic spines. Neuron, 61(2):247‐258. [PMC complimentary article] [PubMed] [Google Scholar]

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813191/