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Spontaneous network activity in development and neurodevelopmental disorders

Supervisors: Ole Paulsen, Susanna Mierau

Multiple mutations in synaptic proteins have been identified in genetic forms of autism and related developmental disorders; yet little is known about how these mutations disrupt synaptic and network function leading to lifelong difficulties with social interaction, communication and sensory processing. In this project, we will investigate the fundamental rules that govern the development of network activity in cortical neurons and how this process is disrupted in a mouse model of autism. Student will use multi-electrode array recordings to investigate the development of network activity in primary neuronal cultures from Mecp2-deficient and wild-type type mice. A combined experimental and computational project, the student will use optogenetic stimulation and/or silencing of specific cell-types to elucidate the contribution of excitatory and inhibitory neuronal populations to network development. The student will also apply and create novel methods for analyzing the development of neuronal network activity through our collaborations with research groups in the Maths and Engineering departments. Prior experience with computational methods preferred. Strong programming and maths skills are required. An additional computational supervisor can be arranged for the project based on student interests. This project will have full utilization of the resources and equipment in the Neuronal Oscillations Group.

Relevant references

Mierau, S.B., Patrizi, A., Hensch, T.K., Fagiolini, M. Cell-specific regulation of NMDA receptor maturation by Mecp2 in cortical circuits. Biological Psychiatry 2016 May 1;79(9):746-54.

Cotterill E, Charlesworth P, Thomas CW, Paulsen O, Eglen SJ. A comparison of computational methods for detecting bursts in neuronal spike trains and their application to human stem cell-derived neuronal networks.  J Neurophysiol. 2016 Apr 20;116(2):306-21.

Schroeter MS, Charlesworth P, Kitzbichler MG, Paulsen O, Bullmore ET. Emergence of rich-club topology and coordinated dynamics in development of hippocampal functional networks in vitro. J Neurosci. 2015 Apr 8;35(14):5459-70.