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Monday, July 20 • 8:00pm - 9:00pm
P129: Correlated inputs to the striatum generate beta over-synchronization in in silico cortico-basal ganglia network

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Elena Manferlotti, Matteo Vissani, Arvind Kumar, Alberto Mazzoni

Parkinson’s Disease (PD) is known to be associated with over-synchronized oscillations in the beta frequency range (13-35Hz) in motor cortex and basal ganglia (BG) [1]. Although the mechanisms underlying the emergence of these oscillations are poorly understood, several excitatory-inhibitory loops have been identified in the cortex-BG networks that might initiate or generate them.

Recent experimental data suggests that striatal spiny projection neurons (SPNs) are phase locked to the beta oscillation cycles [2]. Indeed, transient change in the SPNs firing rate is sufficient to unleash oscillations into the mutually connected globus pallidus externus (GPe) sub-thalamic nucleus (STN) network [3].

Here, we investigate the effect of temporal synchrony of SPNs activity on beta oscillations simulating a biologically plausible BG model with spiking neurons [4]. The likely source of correlations in the SPNs is thalamo-cortical input, since striatal connectivity is too sparse. Therefore, we injected correlated inputs to the SPNs. Our model showed the emergence of beta band aberrant synchronization as the network switches from the uncorrelated to the correlated input. Crucially, inputs displayed a fixed firing rate, that is the over-synchronization emerged only because of the input synchrony. Furthermore, increased input correlation resulted in enhanced Globus Pallidus internus (GPi) firing rate as observed experimentally [5]. Next, we investigated the possible consequences of these results for Deep Brain Stimulation (DBS) simulating high frequency injections into the STN. Our preliminary results showed that even a short window of stimulation was enough to reduce beta oscillations in the firing rate of STN, GPe and GPi nuclei.

Our study provides innovative observations about the origin and propagation of PD-related beta oscillations in the BG and their reduction due to DBS. It paves the way toward in silico testing of DBS parameters that could be used to determine optimal parameters of stimulation offline rather than during surgical implants.

References

1\. Oswal A, Brown P, Litvak V. Synchronized neural oscillations and the pathophysiology of Parkinson’s disease. Curr Opin Neurol. 2013;26:662–70.

2\. Sharott A et al. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations. J Neurosci. 2017;37:9977–98.

3\. Mirzaei A et al. Sensorimotor processing in the basal ganglia leads to transient beta oscillations during behavior. Journal of Neuroscience. 2017 Nov 15;37(46):11220-32.

4\. Lindahl M, Hellgren Kotaleski J. Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model. eNeuro. 2016;3:ENEURO.0156-16.2016.

5\. Magnin M, Morel A, Jeanmonod D. Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience. 2000;96:549–64.

To partecipate to my poster presentation, please click on this link: https://meet.google.com/mwn-gwmt-act

Speakers
avatar for Elena Manferlotti

Elena Manferlotti

Intern at the BioRobotics Institute, Pontedera (PI), The Biorobotics Institute and Department of Excellence for Robotics and AI, SSSA
I am an ambitious and motivated person who has developed a strong interest in neuroscience. Specially focused on signal analysis and modelling. Main research interest: Parkinson's disease and cortico - basal ganglia circuits.



Monday July 20, 2020 8:00pm - 9:00pm CEST
Slot 15