Regulation and control roles of the basal ganglia in the development of absence epileptiform activities

Abstract

Absence epileptiform activities are traditionally considered to be primarily induced by abnormal interactions between the cortical and thalamic neurons, which form the thalamocortical circuit in the brain. The basal ganglia, as an organizational unit in the brain, has close input and output relationships with the thalamocortical circuit. Although several studies report that the basal ganglia may participate in controlling and regulating absence epileptiform activities, to date, there have been no studies regarding whether the basal ganglia directly cause absence epileptiform activities. In this paper, we built a basal ganglia-corticothalamic network model to determine the role of basal ganglia in this disease. We determined that absence epileptiform activities might be directly induced by abnormal coupling strengths on certain pivotal pathways in the basal ganglia. These epileptiform activities can be well controlled by the coupling strengths of three major pathways that project from the thalamocortical network to the basal ganglia. The results implied that the substantia nigra pars compacta (SNc) can be considered to be the effective treatment target area for inhibiting epileptiform activities, which supports the observations of previous studies. Particularly, as a major contribution of this paper, we determined that the final presentation position of the epileptic slow spike waves is not limited to the cerebral cortex; these waves may additionally appear in the thalamus, striatal medium spiny neurons, striatal fast spiking interneuron, the SNc, subthalamic nucleus, substantia nigra pars reticulata and globus pallidus pars externa. In addition, consistent with several previous studies, the delay in the network was observed to be a critical factor for inducing transitions between different types of absence epileptiform activities. Our new model not only explains the onset and control mechanism but also provides a unified framework to study similar problems in neuron systems.

Appendix

Unless otherwise noted, we used the following values for numerical simulations:

Parameter	Meaning of parameter	Unit	Values	References
$Q_{e}^{max},Q_{i}^{max}$	The MFR of the cortex	Hz	250	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005)
$Q_{m}^{max}$	The MFR of the MSN	Hz	65	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$Q_{f}^{max}$	The MFR of the FSI	Hz	70	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$Q_{p_{1}}^{max}$	The MFR of the SNr	Hz	250	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$Q_{p_{2}}^{max}$	The MFR of the GPe	Hz	300	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$Q_{c}^{max}$	The MFR of the SNc	Hz	300	Estimated
$Q_{s}^{max}$	The MFR of the SRN	Hz	250	Robinson et al. (2002) , Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005)
$Q_{\zeta }^{max}$	The MFR of the STN	Hz	500	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$Q_{r}^{max}$	The MFR of the TRN	Hz	250	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005)
$\theta _{e},\theta _{i}$	The MTP of the cortex	mV	15	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005), Robinson et al. (2004)
$\theta _{m}$	The MTP of the MSN	mV	19	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$\theta _{f}$	The MTP of the FSI	mV	10	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$\theta _{p_{2}}$	The MTP of the GPe	mV	9	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$\theta _{p_{1}}$	The MTP of the SNr	mV	10	van Albada and Robinson (2009); van Albada et al. (2009), Chen et al. (2014, 2015b)
$\theta _{\zeta }$	The MTP of the STN	mV	10	van Albada and Robinson 2009; van Albada et al. 2009, Chen et al. (2014, 2015b)
$\theta _{r}$	The MTP of the TRN	mV	15	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005), Robinson et al. (2004)
$\theta _{s}$	The MTP of the SRN	mV	15	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005), Robinson et al. (2004)
$\theta _{c}$	The MTP of the SNc	mV	10	Estimated
$\gamma _{e}$	Cortical dam** rate	Hz	100	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005)
$\tau$	The delay	ms	55	Marten et al. (2009a), Chen et al. (2014, 2015b)
$\alpha$	Synaptodendritic decay time	$s^{-1}$	50	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005), Robinson et al. (2004)
$\sigma$	Standard deviation of firing thresholds	mV	6	Robinson et al. (2002), Chen et al. (2014, 2015b), Breakspear et al. (2005), Robinson et al. (2004)
$\beta$	Synaptodendritic rise time	$s^{-1}$	200	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005), Robinson et al. (2004)
$V_{s}$	The sensory stimuli constant	mV s	2.1	Estimated

Coupling strength	The output nuclei	The receiving nuclei	Values (mV s)	References
$\nu _{ei}$	IIN	EPN	− 1.6	Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005)
$\nu _{ee}$	EPN	EPN	1.1	Marten et al. (2009a), Chen et al. (2014, 2015b), Breakspear et al. (2005)
$\nu _{rs}$	SRN	TRN	0.51	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b)
$\nu _{re}$	EPN	TRN	0.052	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b)
$\nu _{sr}^{A,B}$	TRN	SRN	− 2.3	Robinson et al. (2002), Chen et al. (2014, 2015b), Robinson et al. (2004)
$\nu _{me}$	EPN	MSN	1.1	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{mm}$	MSN	MSN	− 0.22	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{ms}$	SRN	MSN	0.12	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{fe}$	EPN	FSI	0.72	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{fc}$	SNc	FSI	0.35	Estimated
$\nu _{mc}$	SNc	MSN	0.35	Estimated
$\nu _{p_{1}m}$	MSN	SNr	− 0.08	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{p_{1}p_{2}}$	GPe	SNr	− 0.031	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{p_{1}\zeta }$	STN	SNr	0.32	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{p_{2}m}$	MSN	GPe	− 0.31	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{p_{2}p_{2}}$	GPe	GPe	− 0.07	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{p_{1}p_{1}}$	SNr	SNr	− 0.006	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{p_{2}\zeta }$	STN	GPe	0.47	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{\zeta p_{2}}$	GPe	STN	− 0.042	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{es}$	SRN	EPN	1.9	Robinson et al. (2002), Marten et al. (2009a), Chen et al. (2014, 2015b)
$\nu _{se}$	EPN	SRN	2.1	Robinson et al. (2002), Chen et al. (2014, 2015b)
$\nu _{sp_{1}}$	SNr	SRN	− 0.03	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{\zeta e}$	EPN	STN	0.15	van Albada and Robinson (2009) van Albada et al. (2009), Chen et al. (2014, 2015b)
$\nu _{rp_{1}}$	SNr	TRN	− 0.03	Chen et al. (2014, 2015b)
$\nu _{ep_{2}}$	GPe	EPN	− 0.04	Chen et al. (2015b)
$\nu _{ep_{1}}$	SNr	EPN	− 0.04	Estimated
$\nu _{mf}$	FSI	MSN	− 0.3	van Albada and Robinson (2009), van Albada et al. (2009), Chen et al. (2014, 2015b)