Loading…
CNS*2020 Online has ended
Welcome to the Sched instance for CNS*2020 Online! Please read the instruction document on detailed information on CNS*2020.
Back To Schedule
Sunday, July 19 • 9:00pm - 10:00pm
P117: The interplay of neural mechanisms regulates spontaneous cortical network activity: Inferring the role of key mechanisms using data-driven modeling

Log in to save this to your schedule, view media, leave feedback and see who's attending!

Feedback form is now closed.
Jugoslava Acimovic, Tiina Manninen, Heidi Teppola, Marja-Leena Linne

*************************************************
Link to Zoom for poster presentation: 

https://tuni.zoom.us/j/2645809088

*************************************************

In isolated neural systems devoid of external stimuli, the exchange between neuronal, synaptic and putatively also glial mechanisms gives rise to spontaneous self-sustained synchronous activity. This phenomenon has been extensively documented in dissociated cortical cultures in vitro that are routinely used to study neural mechanisms in health and disease. We examine these mechanisms using a new data-driven computational modeling approach. The approach integrates standard spiking network models, non-standard glial mechanisms and network-level experimental data.

The experimental data represents spontaneous activity in dissociated rat cortical cultures recorded using microelectrode arrays. The recordings were performed under several experimental protocols that involved pharmacological manipulation of network activity. Under each protocol the activity exhibited characteristic network bursts, the short intervals (100ms to 1s) of intensive network-wide spiking interleaved by longer (~10s) periods of sparse uncorrelated spikes. The data was analysed to extract, among other properties, duration, intensity and frequency of burst events [1].

The computational model incorporates fast burst propagation and decay mechanisms, as well as the slower burst initiation mechanisms. We first constructed the fast part of the model as a generic spiking neuronal network and optimized it to the experimental data describing intra-burst properties. We developed a model fitting routine relying on multi-objective optimization [2]. The optimized ‘fast’ model was then extended with a selected astrocytic mechanism operating on a similar time-scale as the network burst initiation [3]. Typically, the burst initiation is attributed to a combination of noisy inputs and the dynamics of neuronal (and synaptic) adaptation currents. While noise provides necessary depolarization of cell membrane the adaptation currents prohibit fast initiation of the next burst event. The noise might account for the randomness in ion channel opening and closing, the spontaneous synaptic release and other sources of randomness. The adaptation accounts for the kinetics of various ion channels. We explore the role of a non-standard deterministic mechanism introduced through slow inward current from astrocytes to neurons.

We demonstrate that the fast neuronal part of the model successfully reproduces intra-burst dynamics, including the duration and intensity of network bursts. The model is flexible enough to account for several experimental conditions. Coupled to the slower astrocyte-neuron interaction mechanism the system becomes capable of generating bursts with the frequency proportional to the one seen in vitro.

[1] Teppola H, Aćimović J, Linne M-L (2019) Front Cell Neurosci, 13(377):1-22

[2] Aćimović J, Teppola H, Mäki-Marttunen T, Linne M-L (2018) BMC Neurosci 19(2):68-69

[3] Aćimović J, Manninen T, Teppola H, van Albada S, Diesmann M, Linne M-L (2019) BMC Neurosci, 20(1):97

Acknowledgements: This research has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2). The funding has also been received from the Academy of Finland through grants No. 297893, 326494, 326495.



Speakers
avatar for Jugoslava Acimovic

Jugoslava Acimovic

Senior researcher, Faculty of Medicine and Health Technology, Tampere University



Sunday July 19, 2020 9:00pm - 10:00pm CEST
Slot 16