title: Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain.
abstract: Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers.
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095;
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Forsyth
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213;
authors.forename: Peter
authors.initials: P
authors.lastname: Bachman
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA 94143; San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121;
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.affiliation: San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121;
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Roach
authors.affiliation: Department of Psychology, University of California, Los Angeles, CA 90095; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA 90095 rasarnow@mednet.ucla.edu.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Asarnow
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003523:Cycloserine / Q000494:pharmacology; D003710:Demography; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005260:Female; D006801:Humans; D007858:Learning; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D010775:Photic Stimulation; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013647:Task Performance and Analysis; D055815:Young Adult
chemical_list: D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine
keywords: NMDA receptor; d-cycloserine; learning; long-term potentiation; neuroplasticity