TY - JOUR
T1 - Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model
AU - van den Boom, Bastijn J. G.
AU - Elhazaz-Fernandez, Alfredo
AU - Rasmussen, Peter A.
AU - van Beest, Enny H.
AU - Parthasarathy, Aishwarya
AU - Denys, Damiaan
AU - Willuhn, Ingo
N1 - Funding Information: We thank Dr. Tycho M. Hoogland, Andres de Groot, Mike Vink, and Joop Bos for technical support for imaging experiments. We are grateful to Ralph Hamelink, Dr. Nicole Yee, and Dr. Arthur S.C. França for technical assistance. We are thankful to Bart Kok and Makaela Weeda for assisting with histology. We thank Dr. Marcus H.C. Howlett, Dr. Matthijs G.P. Feenstra, and Dr. Ester Visser for their comments on the manuscript. We are grateful to the UCLA Miniscope team for sharing the blueprints of the miniscopes. We thank the team of Dr. Karl Deisseroth for advice on the use of viral vectors. We thank Lucia Economico for the mouse illustration. We acknowledge support from the Gravitation program of the Dutch Research Council grant, BRAINSCAPES (024.004.012) (I.W.), and a research grant from FFOR, the Foundation for OCD Research (I.W.). Funding Information: We thank Dr. Tycho M. Hoogland, Andres de Groot, Mike Vink, and Joop Bos for technical support for imaging experiments. We are grateful to Ralph Hamelink, Dr. Nicole Yee, and Dr. Arthur S.C. França for technical assistance. We are thankful to Bart Kok and Makaela Weeda for assisting with histology. We thank Dr. Marcus H.C. Howlett, Dr. Matthijs G.P. Feenstra, and Dr. Ester Visser for their comments on the manuscript. We are grateful to the UCLA Miniscope team for sharing the blueprints of the miniscopes. We thank the team of Dr. Karl Deisseroth for advice on the use of viral vectors. We thank Lucia Economico for the mouse illustration. We acknowledge support from the Gravitation program of the Dutch Research Council grant, BRAINSCAPES (024.004.012) (I.W.), and a research grant from FFOR, the Foundation for OCD Research (I.W.). Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.
AB - Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.
UR - http://www.scopus.com/inward/record.url?scp=85169690162&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-023-41026-x
DO - https://doi.org/10.1038/s41467-023-41026-x
M3 - Article
C2 - 37666830
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5385
ER -