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 magnetic resonance spectroscopy (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 Receptors 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 (a) an increase in level of neuronal activity, (b) an increase in BOLD and (c) 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.

APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice

“…1 H NMR spectroscopy. All animal procedures for in vivo proton MR spectroscopy were performed as described previously 81,82 , and in accordance with the National Institutes of Health guidelines with approval from the Institutional Animal Care and Use Committee at the Nathan S. Kline Institute for Psychiatric Research. All animals were anesthetized using an isoflurane vaporizer set at the following percentages: 3% for induction, 2% during pilot scanning and 1.5% during data acquisition.…”

Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: a multimodal fMRI and 1H-MRS study

“…NAAG induces a vasodilatory response in local blood vessels, via being exported from neurons to astrocytes where it binds to the mGluR3 glutamate receptor. This results in the release of vasoactive agents, which is in turn associated with an increase in the BOLD response [Baslow et al, 2016]. Further evidence that NAAG is associated with BOLD comes from the pharmacological inhibition of NAAG breakdown, which causes an increase in the BOLD response for a few minutes [Baslow et al, 2005].…”

Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex

“…Baslow and coworkers (Baslow, 2002;Baslow et al, 2007;Baslow et al, 2016) proposed that NAA might additionally function as molecular water pump (MWP), able of removing excess water produced by increased glucose respiration during neuronal activation. According to this hypothesis, NAA is actively transported to the extracellular space in conjuction with bound water molecules.…”