On the role of intrastriatal connectivity among SPNs and interneurons and its effect on population activity

On the role of intrastriatal connectivity among SPNs and interneurons and its effect on population activity

Johanna Frost Nylen¹, JJ Johannes Hjorth², Wilhelm Thunberg¹, Alexander Kozlov², Ilaria Carannante², Jeanette Hellgren Kotaleski², Sten Grillner¹

¹Department of Neuroscience, Karolinska Institute, Stockholm

²Science for Life Laboratory, School of Electrical Engineering and Computer Science, KTH Royal Institute of Technology, Stockholm

The striatum is the main input nucleus of the basal ganglia, a collection of subcortical nuclei which are involved in action selection, motor learning and habit formation. The intrastriatal connectivity consists of connections between and within the two major cell types, the SPNs (striatal projection neurons) of the direct and indirect pathways, which project to downstream basal ganglia nuclei. The SPNs have sparse collateral projections which target distal dendrites. In addition, there are several interneuron types which contribute to the GABAergic inhibition which occurs in the striatum, including fast spiking interneurons (FS) and low threshold spiking interneurons (LTS). The relative importance of the interneuronal inhibition and the local inhibition among SPNs is poorly understood on the population level. Using a framework for creating and simulating detailed large scale microcircuit simulation, Snudda, we construct a striatal microcircuit based on detailed electrophysiological and anatomical data (Hjorth et al., 2020, 2021, Frost-Nylén et al., 2021) containing networks of different size from 10.000 neurons to the complete striatum (approx. 850.000 neurons – one hemisphere). We investigate the connectivity within the network in terms of the number of synapses between selected subpopulations and the number of presynaptic neurons. We then manipulate the circuit through ablation of connections between the specific cell types and investigate how this affects the activation of populations within striatum. Additionally, we simulate single neurons of dSPN and iSPN with appropriate distribution of gabaergic synapses to reveal the effect of lateral inhibition on distal dendrites and the interaction with discrete populations of excitatory neurons from cortex and thalamus and the formation of plateau potentials. The effect of dopaminergic modulation of the population activity is investigated.

References

Frost Nylen J, Hjorth JJJ, Grillner S and Hellgren Kotaleski J (2021) Dopaminergic and Cholinergic Modulation of Large Scale Networks In silico Using Snudda. Front. Neural Circuits 15:748989. doi: 10.3389/fncir.2021.748989

Hjorth, J., Kozlov, A., Carannante, I., Frost Nylén, J., Lindroos, R., Johansson, Y., Tokarska, A., Dorst, M. C., Suryanarayana, S. M., Silberberg, G., Hellgren Kotaleski, J., & Grillner, S. (2020). The microcircuits of striatum in silico. Proceedings of the National Academy of Sciences of the United States of America, 117(17), 9554–9565. https://doi.org/10.1073/pnas.2000671117

Hjorth, J., Hellgren Kotaleski, J., & Kozlov, A. (2021). Predicting Synaptic Connectivity for Large-Scale Microcircuit Simulations Using Snudda. Neuroinformatics, 10.1007/s12021-021-09531-w. Advance online publication. https://doi.org/10.1007/s12021-021-09531-w