Control of absence seizures induced by the pathways connected to SRN in corticothalamic system

Abstract

The cerebral cortex, thalamus and basal ganglia together form an important network in the brain, which is closely related to several nerve diseases, such as parkinson disease, epilepsy seizure and so on. Absence seizure can be characterized by 2–4 Hz oscillatory activity, and it can be induced by abnormal interactions between the cerebral cortex and thalamus. Many experimental results have also shown that basal ganglia are a key neural structure, which closely links the corticothalamic system in the brain. Presently, we use a corticothalamic-basal ganglia model to study which pathways in corticothalamic system can induce absence seizures and how these oscillatory activities can be controlled by projections from the substantia nigra pars reticulata (SNr) to the thalamic reticular nucleus (TRN) or the specific relay nuclei (SRN) of the thalamus. By tuning the projection strength of the pathway “Excitatory pyramidal cortex-SRN”, ”SRN-Excitatory pyramidal cortex” and “SRN–TRN” respectively, different firing states including absence seizures can appear. This indicates that absence seizures can be induced by tuning the connection strength of the considered pathway. In addition, typical absence epilepsy seizure state “spike-and-slow wave discharges” can be controlled by adjusting the activation level of the SNr as the pathways SNr–SRN and SNr–TRN open independently or together. Our results emphasize the importance of basal ganglia in controlling absence seizures in the corticothalamic system, and can provide a potential idea for the clinical treatment.

Appendix

Unless otherwise noted, we use these parameter values for simulations as follows (Chen et al. 2014; Marten et al. 2009; Massimo 2012; Paz et al. 2007; Roberts and Robinson 2008; Rodrigues et al. 2009; van Albada et al. 2009; van Albada and Robinson 2009).

Parameter	Mean	Value
$Q_{e}^{max},Q_{i}^{max}$	Cortical maximum firing rate	250 Hz
$Q_{d_{1}}^{max},Q_{d_{2}}^{max}$	Striatum maximum firing rate	65 Hz
$Q_{p_{1}}^{max}$	SNr maximum firing rate	250 Hz
$Q_{p_{2}}^{max}$	GPe maximum firing rate	300 Hz
$Q_{\zeta }^{max}$	STN maximum firing rate	500 Hz
$Q_{s}^{max}$	SRN maximum firing rate	250 Hz
$Q_{r}^{max}$	TRN maximum firing rate	250 Hz
$\theta _{e},\theta _{i}$	Mean firing threshold of cortical populations	15 mV
$\theta _{d_{1}},\theta _{d_{2}}$	Mean firing threshold of striatum	19 mV
$\theta _{p_{1}}$	Mean firing threshold of SNr	10 mV
$\theta _{p_{2}}$	Mean firing threshold of GPe	9 mV
$\theta _{\zeta }$	Mean firing threshold of STN	10 mV
$\theta _{s}$	Mean firing threshold of SRN	15 mV
$\theta _{r}$	Mean firing threshold of TRN	15 mV
$\gamma _{e}$	Cortical dam** rate	100 Hz
$\tau$	Time delay due to slow synaptic kinetics of $GABA_{B}$	50 ms
$\alpha$	Synaptodendritic decay time constant	50 ${\rm s}^{-1}$
$\beta$	Synaptodendritic rise time constant	200 ${\rm s}^{-1}$
$\sigma$	Threshold variability of firing rate	6 mV
$\phi _{n}$	Nonspecific subthalamic input onto SRN	2 mV s

Coupling strength	Source	Target	Value (mV s)
$\nu _{ee}$	Excitatory pyramidal neurons	Excitatory pyramidal neurons	1
$\nu _{ei}$	Inhibitory interneurons	Excitatory pyramidal neurons	−1.8
$\nu _{re}$	Excitatory pyramidal neurons	TRN	0.05
$\nu _{rs}$	SRN	TRN	0.5
$\nu _{sr}^{A,B}$	TRN	SRN	−0.48
$\nu _{d_{1}e}$	Excitatory pyramidal neurons	Striatal D1 neurons	1
$\nu _{d_{1}d_{1}}$	Striatal D1 neurons	Striatal D1 neurons	−0.2
$\nu _{d_{1}s}$	SRN	Striatal D1 neurons	0.1
$\nu _{d_{2}e}$	Excitatory pyramidal neurons	Striatal D2 neurons	0.7
$\nu _{d_{2}d_{2}}$	Striatal D2 neurons	Striatal D2 neurons	−0.3
$\nu _{d_{2}s}$	SRN	Striatal D2 neurons	0.05
$\nu _{p_{1}d_{1}}$	Striatal D1 neurons	SNr	−0.1
$\nu _{p_{1}p_{2}}$	GPe	SNr	−0.03
$\nu _{p_{1}\zeta }$	STN	SNr	0–0.6
$\nu _{p_{2}d_{2}}$	Striatal D2 neurons	GPe	−0.3
$\nu _{p_{2}p_{2}}$	GPe	GPe	−0.075
$\nu _{p_{2}\zeta }$	STN	GPe	0.45
$\nu _{\zeta p_{2}}$	GPe	STN	−0.04
$\nu _{es}$	STN	Excitatory pyramidal neurons	1.8
$\nu _{se}$	Excitatory pyramidal neurons	SRN	2.2
$\nu _{\zeta e}$	Excitatory pyramidal neurons	STN	0.1
$\nu _{sp_{1}}$	SNr	SRN	−0.035
$\nu _{rp_{1}}$	SNr	TRN	−0.035