An integrate-and-fire model for synchronized bursting in a network of cultured cortical neurons

2006 ◽  
Vol 21 (3) ◽  
pp. 227-241 ◽  
Author(s):  
D. A. French ◽  
E. I. Gruenstein
2004 ◽  
Vol 92 (2) ◽  
pp. 959-976 ◽  
Author(s):  
Renaud Jolivet ◽  
Timothy J. Lewis ◽  
Wulfram Gerstner

We demonstrate that single-variable integrate-and-fire models can quantitatively capture the dynamics of a physiologically detailed model for fast-spiking cortical neurons. Through a systematic set of approximations, we reduce the conductance-based model to 2 variants of integrate-and-fire models. In the first variant (nonlinear integrate-and-fire model), parameters depend on the instantaneous membrane potential, whereas in the second variant, they depend on the time elapsed since the last spike [Spike Response Model (SRM)]. The direct reduction links features of the simple models to biophysical features of the full conductance-based model. To quantitatively test the predictive power of the SRM and of the nonlinear integrate-and-fire model, we compare spike trains in the simple models to those in the full conductance-based model when the models are subjected to identical randomly fluctuating input. For random current input, the simple models reproduce 70–80 percent of the spikes in the full model (with temporal precision of ±2 ms) over a wide range of firing frequencies. For random conductance injection, up to 73 percent of spikes are coincident. We also present a technique for numerically optimizing parameters in the SRM and the nonlinear integrate-and-fire model based on spike trains in the full conductance-based model. This technique can be used to tune simple models to reproduce spike trains of real neurons.


2009 ◽  
Vol 21 (8) ◽  
pp. 2114-2122 ◽  
Author(s):  
Jonathan Touboul

The quadratic adaptive integrate-and-fire model (Izhikevich, 2003 , 2007 ) is able to reproduce various firing patterns of cortical neurons and is widely used in large-scale simulations of neural networks. This model describes the dynamics of the membrane potential by a differential equation that is quadratic in the voltage, coupled to a second equation for adaptation. Integration is stopped during the rise phase of a spike at a voltage cutoff value Vc or when it blows up. Subsequently the membrane potential is reset, and the adaptation variable is increased by a fixed amount. We show in this note that in the absence of a cutoff value, not only the voltage but also the adaptation variable diverges in finite time during spike generation in the quadratic model. The divergence of the adaptation variable makes the system very sensitive to the cutoff: changing Vc can dramatically alter the spike patterns. Furthermore, from a computational viewpoint, the divergence of the adaptation variable implies that the time steps for numerical simulation need to be small and adaptive. However, divergence of the adaptation variable does not occur for the quartic model (Touboul, 2008 ) and the adaptive exponential integrate-and-fire model (Brette & Gerstner, 2005 ). Hence, these models are robust to changes in the cutoff value.


1999 ◽  
Vol 11 (4) ◽  
pp. 935-951 ◽  
Author(s):  
Shigeru Shinomoto ◽  
Yutaka Sakai ◽  
Shintaro Funahashi

Cortical neurons of behaving animals generate irregular spike sequences. Recently, there has been a heated discussion about the origin of this irregularity. Softky and Koch (1993) pointed out the inability of standard single-neuron models to reproduce the irregularity of the observed spike sequences when the model parameters are chosen within a certain range that they consider to be plausible. Shadlen and Newsome (1994), on the other hand, demonstrated that a standard leaky integrate-and-fire model can reproduce the irregularity if the inhibition is balanced with the excitation. Motivated by this discussion, we attempted to determine whether the Ornstein-Uhlenbeck process, which is naturally derived from the leaky integration assumption, can in fact reproduce higher-order statistics of biological data. For this purpose, we consider actual neuronal spike sequences recorded from the monkey prefrontal cortex to calculate the higher-order statistics of the interspike intervals. Consistency of the data with the model is examined on the basis of the coefficient of variation and the skewness coefficient, which are, respectively, a measure of the spiking irregularity and a measure of the asymmetry of the interval distribution. It is found that the biological data are not consistent with the model if the model time constant assumes a value within a certain range believed to cover all reasonable values. This fact suggests that the leaky integrate-and-fire model with the assumption of uncorrelated inputs is not adequate to account for the spiking in at least some cortical neurons.


Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 262
Author(s):  
Qin-Wei Wu ◽  
Josef P. Kapfhammer

The CRISPR-Cas13 system based on a bacterial enzyme has been explored as a powerful new method for RNA manipulation. Due to the high efficiency and specificity of RNA editing/interference achieved by this system, it is currently being developed as a new therapeutic tool for the treatment of neurological and other diseases. However, the safety of this new generation of RNA therapies is still unclear. In this study, we constructed a vector expressing CRISPR-Cas13 under a constitutive neuron-specific promoter. CRISPR-Cas13 from Leptotrichia wadei was expressed in primary cultures of mouse cortical neurons. We found that the presence of CRISPR-Cas13 impedes the development of cultured neurons. These results show a neurotoxic action of Cas13 and call for more studies to test for and possibly mitigate the toxic effects of Cas13 enzymes in order to improve CRISPR-Cas13-based tools for RNA targeting.


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