AUTHOR=Crown Lindsey M. , Agyeman Kofi A. , Choi Wooseong , Zepeda Nancy , Iseri Ege , Pahlavan Pooyan , Siegel Steven J. , Liu Charles , Christopoulos Vasileios , Lee Darrin J. 

TITLE=Theta-frequency medial septal nucleus deep brain stimulation increases neurovascular activity in MK-801-treated mice

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 18 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1372315

DOI=10.3389/fnins.2024.1372315

ISSN=1662-453X

ABSTRACT=Deep brain stimulation (DBS) has shown remarkable success in treating neurological and psychiatric disorders including as Parkinson's disease, essential tremor, dystonia, epilepsy, and obsessive-compulsive disorder. DBS is now being explored to improve cognition and functional outcomes in other psychiatric conditions, such as those characterized by reduced N-methyl-Daspartate (NMDA) function (i.e. schizophrenia). While DBS for movement disorders generally involves high-frequency (> 100 Hz) stimulation, there is evidence that low-frequency stimulation may have beneficial and persisting effects when applied to cognitive brain networks. In this study, we utilize a novel technology, functional ultrasound imaging (fUSI), to characterize the cerebrovascular impact of medial septal nucleus (MSN) DBS under conditions of NMDA antagonism (pharmacologically using Dizocilpine ) in anesthetized male mice.Imaging from a sagittal plane across a variety of brain regions within and outside of the septohippocampal circuit, we find that MSN theta-frequency (7.7Hz) DBS increases hippocampal cerebral blood volume (CBV) during and after stimulation offset. This effect was not present using standard high-frequency DBS stimulation parameters (i.e. gamma [100Hz]).These results indicate the MSN DBS increases circuit-specific hippocampal neurovascular activity in a frequency-dependent manner and does so in ways that continue beyond the period of electrical stimulation.