title: Functional dynamics of hippocampal glutamate during associative learning assessed with in vivo1H functional magnetic resonance spectroscopy.
abstract: fMRI has provided vibrant characterization of regional and network responses associated with associative learning and memory; however, their relationship to functional neurochemistry is unclear. Here, we introduce a novel application of in vivo proton functional magnetic resonance spectroscopy (1H fMRS) to investigate the dynamics of hippocampal glutamate during paired-associated learning and memory in healthy young adults. We show that the temporal dynamics of glutamate differed significantly during processes of memory consolidation and retrieval. Moreover, learning proficiency was predictive of the temporal dynamics of glutamate such that fast learners were characterized by a significant increase in glutamate levels early in learning, whereas this increase was only observed later in slow learners. The observed functional dynamics of glutamate provides a novel in vivo marker of brain function. Previously demonstrated N-methyl-D-aspartate (NMDA) receptor mediated synaptic plasticity during associative memory formation may be expressed in glutamate dynamics, which the novel application of1H MRS is sensitive to. The novel application of1H fMRS can provide highly innovative vistas for characterizing brain function in vivo, with significant implications for studying glutamatergic neurotransmission in health and disorders such as schizophrenia.
authors.affiliation: Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States. Electronic address: jeffrey.stanley@wayne.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stanley
authors.affiliation: Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.
authors.forename: Ashley
authors.initials: A
authors.lastname: Burgess
authors.affiliation: Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.
authors.forename: Dalal
authors.initials: D
authors.lastname: Khatib
authors.affiliation: Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.
authors.forename: Karthik
authors.initials: K
authors.lastname: Ramaseshan
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States; Institute of Gerontology, Wayne State University, Detroit, MI, United States.
authors.forename: Muzamil
authors.initials: M
authors.lastname: Arshad
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.
authors.forename: Helen
authors.initials: H
authors.lastname: Wu
authors.affiliation: Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States.
authors.forename: Vaibhav A
authors.initials: VA
authors.lastname: Diwadkar
mesh_terms: D000328:Adult; D001245:Association Learning / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000502:physiology; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
chemical_list: D018698:Glutamic Acid
keywords: Associative learning and memory; Functional; Glutamate; In vivo; MRS