Based on our result on the influence of adaptation and pacemaker neurons, the emergent bursting behavior should prove very difficult to repress in unstructured cultures if they are triggered by pacemaker neurons, that is unless a way of removing the pacemaker neurons can be found. To tackle this issue, I propose to use patterned cultures, where the connectivity would be structured in such a way that the excitation from the pacemaker neurons cannot propagate and recruit the whole network.
In order to take the relevant spatiotemporal correlations that are present in neuronal cultures into account, the networks that we study must contain the spatial information of the cell positions and connection lengths.
In homogeneous cultures, this can be performed rather effectively using generative models, and the NNGT library allows versatile network generation in spatial environments. This first step allowed us to study the detailed spatiotemporal dynamics of burst nucleation in homogeneous cultures.
However, such simple models become more and more inaccurate as the spatial complexity increases, especially in structured cultures, where obstacles can block the neurites’ path, making the actual connection distance often much larger than the euclidean distance between the two neurons.
DeNSE: a new growth simulator¶
To properly take such complex spatial environments into account, the main requirement is the implementation of a parallel simulator, DeNSE, which can model the growth process of neurons in 2D cultures. Moreover, beyond spatial cultures, the goal of this simulator is also to provide biologically detailed mechanisms for neurite outgrowth so that it can help isolate relevant factors in the growing process.
As of July 2019, a pre-release of the simulator is available on GitHub (https://github.com/SENeC-Initiative/DeNSE) and its documentation is present on ReadTheDocs (https://dense.readthedocs.io/en/latest/).
Examples of structures obtained through the DeNSE simulator. On the left is a multipolar neuron with limited arborization obtained through lateral branching. One the right is a purkinje-like cell displaying an exhuberant dendritic arbor which stems from a combination of initial splits and later interstitial branching events. Axons are marked in red, dendrites in blue, somas in black. Scale bars are 50 :math:`mu`m.
Two chambers with asymmetrical funnels formign an effective neuronal diode: axons from the left chamber can innervate the right chamber while the reverse is a lot less likely.
On the simulated cultures, dendrites are in blue, left axons in orange and right axons in green.