title: Stimulation-induced transient changes in neuronal activity, blood flow and N-acetylaspartate content in rat prefrontal cortex: a chemogenetic fMRS-BOLD study.
abstract: Brain activation studies in humans have shown the dynamic nature of neuronal N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) based on changes in their MRS signals in response to stimulation. These studies demonstrated that upon visual stimulation there was a focal increase in cerebral blood flow (CBF) and a decrease in NAA or in the total of NAA and NAAG signals in the visual cortex, and that these changes were reversed upon cessation of stimulation. In the present study we have developed an animal model in order to explore the relationships between brain stimulation, neuronal activity, CBF and NAA. We use "designer receptor exclusively activated by designer drugs" (DREADDs) technology for site-specific neural activation, a local field potential electrophysiological method for measurement of changes in the rate of neuronal activity, functional MRS for measurement of changes in NAA and a blood oxygenation level-dependent (BOLD) MR technique for evaluating changes in CBF. We show that stimulation of the rat prefrontal cortex using DREADDs results in the following: (i) an increase in level of neuronal activity; (ii) an increase in BOLD and (iii) a decrease in the NAA signal. These findings show for the first time the tightly coupled relationships between stimulation, neuron activity, CBF and NAA dynamics in brain, and also provide the first demonstration of the novel inverse stimulation-NAA phenomenon in an animal model.
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
authors.forename: Morris H
authors.initials: MH
authors.lastname: Baslow
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.|Department of Child and Adolescent Psychiatry, New York University Langone School of Medicine, 560 1st Avenue, New York, NY, 10016, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Cain
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.|Department of Child and Adolescent Psychiatry, New York University Langone School of Medicine, 560 1st Avenue, New York, NY, 10016, USA.|Department of Neuroscience and Physiology, New York University Langone School of Medicine, 560 1st Avenue, New York, NY, 10016, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sears
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.|Department of Child and Adolescent Psychiatry, New York University Langone School of Medicine, 560 1st Avenue, New York, NY, 10016, USA.|Department of Neuroscience and Physiology, New York University Langone School of Medicine, 560 1st Avenue, New York, NY, 10016, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Wilson
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
authors.forename: Alvin
authors.initials: A
authors.lastname: Bachman
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Gerum
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Guilfoyle
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001783:Blood Flow Velocity / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D009474:Neurons / Q000502:physiology; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: N-acetylaspartate; N-acetylaspartylglutamate; cerebral blood flow; depolarization; designer drug; genetic engineering; local field potential