Vesicle number does not predict postsynaptic measures of miniature synaptic activity frequency in cultured cortical neurons

Mackenzie, Paul J.; Kenner, Gail S.; Prange, Oliver; Murphy, Timothy H.

doi:10.1016/s0306-4522(00)00089-0

Cited by 8 publications

(6 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data on spontaneous release frequencies of vesicles are still scarce and we found only one such study (Mackenzie et al, 2000 ). Experimentally, the maximum spontaneous vesicle release rate found was 0.25 Hz.…”

Section: Methodsmentioning

confidence: 90%

Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution

Wiljes

Elburg

Biehl

et al. 2015

Front. Comput. Neurosci.

View full text Add to dashboard Cite

Internal coordination models hold that early nervous systems evolved in the first place to coordinate internal activity at a multicellular level, most notably the use of multicellular contractility as an effector for motility. A recent example of such a model, the skin brain thesis, suggests that excitable epithelia using chemical signaling are a potential candidate as a nervous system precursor. We developed a computational model and a measure for whole body coordination to investigate the coordinative properties of such excitable epithelia. Using this measure we show that excitable epithelia can spontaneously exhibit body-scale patterns of activation. Relevant factors determining the extent of patterning are the noise level for exocytosis, relative body dimensions, and body size. In smaller bodies whole-body coordination emerges from cellular excitability and bidirectional excitatory transmission alone. Our results show that basic internal coordination as proposed by the skin brain thesis could have arisen in this potential nervous system precursor, supporting that this configuration may have played a role as a proto-neural system and requires further investigation.

show abstract

Section: Methodsmentioning

confidence: 90%

Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution

Wiljes

Elburg

Biehl

et al. 2015

Front. Comput. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Furthermore, synaptic density in cultured cells is considerably lower than that found in vivo, reducing the likelihood of signal spillover. In previous studies using dissociated cultures, we reconstructed sites of MSCTs and found that most Ca 2ϩ transient initiation sites were associated with a single presynaptic terminal (Mackenzie et al, 2000); however, it is conceivable that some differences in Ca 2ϩ transient frequency may be caused by differences in synapse or release site number. Line-plot analysis of Ca 2ϩ -induced changes in fluorescence during repeated MSCTs indicated little spatial variation (within the limits of light microscopy and our imaging conditions) with regard to Ca 2ϩ transient initiation points during multiple events at presumably the same synapse (Fig.…”

Section: Imaging Of Asynchronous Postsynaptic Activity After Train Stmentioning

confidence: 99%

Optical Postsynaptic Measurement of Vesicle Release Rates for Hippocampal Synapses Undergoing Asynchronous Release during Train Stimulation

Otsu

Murphy²

2004

J. Neurosci.

View full text Add to dashboard Cite

Developing hippocampal neurons in microisland culture were found to undergo rapid depression of excitatory synaptic activity caused by consumption of their readily releasable pool (RRP) of vesicles in response to 20 Hz trains of stimulation. Associated with depression was a switch to an asynchronous release mode that maintained transmission at a high steady-state rate equivalent to ϳ2.1 RRPs per second. We have applied postsynaptic Ca 2ϩ imaging to directly monitor these asynchronous release events to estimate both the steady rate of transmitter release and the number of quanta within the RRP at individual hippocampal synapses. Based on the frequency of asynchronous release measured at individual synapses postsynaptically using Ca 2ϩ imaging (5-17 sec after train stimulation) and with knowledge of the time course by which asynchronous release rates decay, we estimate that individual hippocampal synapses exhibit (in response to train stimulation) peak release rates of up to 21 quanta per second from an RRP that contains, on average, 10 quanta. Use-dependent block of evoked synaptic activity by MK-801 [(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate] confirmed that synapses undergoing asynchronous release are not significantly different from the general population with regard to their composition of NMDA receptor and/or release probability. Given that high-frequency trains deplete the synapse of readily releasable quanta (and that these release rates can only be maintained for a few seconds), these high rates of asynchronous release likely reflect refilling of vesicles from a reserve pool and not necessarily the continuous action of a relatively slow clathrin-and endosomedependent process.

show abstract

“…This noise could not only influence the synaptic variability, but also the transmission of information (Jacobson et al, 2005). Thus, while some studies do not support our hypothesis of the contribution of the number of vesicles in synaptic noise (Mackenzie et al, 2000), several others (Korn et al, 1993; Franks et al, 2003; Faisal et al, 2008; Pulido and Marty, 2017) inspired us to include additional synaptic noise in our model. Finally, we also validated our method by building three different in silico data sets where the mean N RRP was set to 1, 4 and 10, respectively.…”

Section: Discussionmentioning

confidence: 79%

Estimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in the Neocortex

Barros-Zulaica

Rahmon

Chindemi

et al. 2019

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

Previous studies based on the ‘Quantal Model’ for synaptic transmission suggest that neurotransmitter release is mediated by a single release site at individual synaptic contacts in the neocortex. However, recent studies seem to contradict this hypothesis and indicate that multi-vesicular release (MVR) could better explain the synaptic response variability observed in vitro. In this study we present a novel method to estimate the number of release sites per synapse, also known as the size of the readily releasable pool (NRRP), from paired whole-cell recordings of connections between layer 5 thick tufted pyramidal cell (L5_TTPC) in the juvenile rat somatosensory cortex. Our approach extends the work of Loebel et al. (2009) by leveraging a recently published data-driven biophysical model of neocortical tissue. Using this approach, we estimated NRRP to be between two to three for synaptic connections between L5_TTPCs. To constrain NRRP values for other connections in the microcircuit, we developed and validated a generalization approach using published data on the coefficient of variation (CV) of the amplitudes of post-synaptic potentials (PSPs) from literature and comparing them against in silico experiments. Our study predicts that transmitter release at synaptic connections in the neocortex could be mediated by MVR and provides a data-driven approach to constrain the MVR model parameters in the microcircuit.

show abstract

Vesicle number does not predict postsynaptic measures of miniature synaptic activity frequency in cultured cortical neurons

Cited by 8 publications

References 53 publications

Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution

Modeling spontaneous activity across an excitable epithelium: Support for a coordination scenario of early neural evolution

Optical Postsynaptic Measurement of Vesicle Release Rates for Hippocampal Synapses Undergoing Asynchronous Release during Train Stimulation

Estimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in the Neocortex

Contact Info

Product

Resources

About