TY - JOUR
T1 - The effect of alterations of schizophrenia-associated genes on gamma band auditory steadystate responses
AU - Metzner, Christoph
AU - Karni, Gili
AU - McMahon-Cole, Hana
AU - Mäki-Marttunen, Tuomo
AU - Steuber, Volker
N1 - © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium,
provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/
publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
PY - 2019/11/14
Y1 - 2019/11/14
N2 - Recent GWAS have identified more than 100 risk genes for schizophrenia (SCZ) [1]. Many of these encode ion channels. While their function has been well characterized, the contributions of common variation in these channels to SCZ pathology remain elusive. Here, we explored the effects of altered kinetics of voltage-gated ion channels on gamma range auditory steady-state (ASSR) deficits, a common biomarker for SCZ [2]. We used a network model of coupled E and I neurons [3].We modified the parameters of single cells in a way that mimics the expected effects of common variants associated with SCZ [4, 5].We included a total of 86 variants of the following genes: CACNA1C, CACNA1D, CACNB2, SCN1A, and HCN1 [5]. We then simulated a click train paradigm with stimulation at 40 Hz, to investigate gamma ASSR deficits. Overall, not surprisingly, we found that almost all genetic variants had a small effect on gamma power (72/86 had gamma power change<15%). However, we identified few variants that either strongly reduced or strongly increased gamma power. Interestingly, these were exclusively variants of genes encoding Ca currents subunits. Furthermore, the variants resulting in reduced gamma power also produced a strong component in the theta range. These changes in spectral composition were caused by changes in the offset and the slope of parameter ‘m’ of the high-voltage activated Ca channel. Our results deepen the understanding of gamma range ASSR deficits in patients suffering from SCZ. All scripts will be freely available (https://github.com/ChristophMetzner) and integrated into the ASSRUnit software package [6].
AB - Recent GWAS have identified more than 100 risk genes for schizophrenia (SCZ) [1]. Many of these encode ion channels. While their function has been well characterized, the contributions of common variation in these channels to SCZ pathology remain elusive. Here, we explored the effects of altered kinetics of voltage-gated ion channels on gamma range auditory steady-state (ASSR) deficits, a common biomarker for SCZ [2]. We used a network model of coupled E and I neurons [3].We modified the parameters of single cells in a way that mimics the expected effects of common variants associated with SCZ [4, 5].We included a total of 86 variants of the following genes: CACNA1C, CACNA1D, CACNB2, SCN1A, and HCN1 [5]. We then simulated a click train paradigm with stimulation at 40 Hz, to investigate gamma ASSR deficits. Overall, not surprisingly, we found that almost all genetic variants had a small effect on gamma power (72/86 had gamma power change<15%). However, we identified few variants that either strongly reduced or strongly increased gamma power. Interestingly, these were exclusively variants of genes encoding Ca currents subunits. Furthermore, the variants resulting in reduced gamma power also produced a strong component in the theta range. These changes in spectral composition were caused by changes in the offset and the slope of parameter ‘m’ of the high-voltage activated Ca channel. Our results deepen the understanding of gamma range ASSR deficits in patients suffering from SCZ. All scripts will be freely available (https://github.com/ChristophMetzner) and integrated into the ASSRUnit software package [6].
U2 - 10.1186/s12868-019-0538-0
DO - 10.1186/s12868-019-0538-0
M3 - Meeting abstract
SN - 1471-2202
VL - 20
SP - 157
EP - 158
JO - BMC Neuroscience
JF - BMC Neuroscience
IS - (Suppl 1)
M1 - 56
T2 - 28th Annual Computational Neuroscience Meeting
Y2 - 13 July 2019 through 17 July 2019
ER -