Stimulation‐induced transient changes in neuronal activity, blood flow and N‐acetylaspartate content in rat prefrontal cortex: a chemogenetic fMRS‐BOLD study. (3rd October 2016)

• Record Type: Journal Article
• Authors: Baslow, Morris H.; Cain, Christopher K.; Sears, Robert; Wilson, Donald A.; Bachman, Alvin; Gerum, Scott; Guilfoyle, David N.
• Is Part Of: NMR in biomedicine. Volume 29:Number 12(2016:Dec.)
• Page Start: 1678
• Page End: 1687
• Publication Date: 2016-10-03
• Subjects: cerebral blood flow -- depolarization -- designer drug -- genetic engineering -- local field potential -- N‐acetylaspartate -- N‐acetylaspartylglutamate; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3629
• Languages: English
• ISSNs: 0952-3480

Abstract

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. Abstract : Using the chemogenetic approach known as designer receptors exclusively activated by designer drugs for stimulation of neuronal activity in a rat model, we have demonstrated an inverse relationship between N‐acetylaspartate (NAA) content and stimulation previously observed in humans. We do this using MRS and MRI. Changes in neuronal activity were also verified with electrophysiological measures. The figure shows the changes in NAA peak amplitude from the chemogenetic modulation.