title: NR2A- and NR2B-NMDA receptors and drebrin within postsynaptic spines of the hippocampus correlate with hunger-evoked exercise.
abstract: Hunger evokes foraging. This innate response can be quantified as voluntary wheel running following food restriction (FR). Paradoxically, imposing severe FR evokes voluntary FR, as some animals choose to run rather than eat, even during limited periods of food availability. This phenomenon, called activity-based anorexia (ABA), has been used to identify brain changes associated with FR and excessive exercise (EX), two core symptoms of anorexia nervosa (AN), and to explore neurobiological bases of AN vulnerability. Previously, we showed a strong positive correlation between suppression of FR-evoked hyperactivity, i.e., ABA resilience, and levels of extra-synaptic GABA receptors in stratum radiatum (SR) of hippocampal CA1. Here, we tested for the converse: whether animals with enhanced expression of NMDA receptors (NMDARs) exhibit greater levels of FR-evoked hyperactivity, i.e., ABA vulnerability. Four groups of animals were assessed for NMDAR levels at CA1 spines: (1) ABA, in which 4 days of FR was combined with wheel access to allow voluntary EX; (2) FR only; (3) EX only; and (4) control (CON) that experienced neither EX nor FR. Electron microscopy revealed that synaptic NR2A-NMDARs and NR2B-NMDARs levels are significantly elevated, relative to CONs'. Individuals' ABA severity, based on weight loss, correlated with synaptic NR2B-NMDAR levels. ABA resilience, quantified as suppression of hyperactivity, correlated strongly with reserve pools of NR2A-NMDARs in spine cytoplasm. NR2A- and NR2B-NMDAR measurements correlated with spinous prevalence of an F-actin binding protein, drebrin, suggesting that drebrin enables insertion of NR2B-NMDAR to and retention of NR2A-NMDARs away from synaptic membranes, together influencing ABA vulnerability.
authors.affiliation: Center for Neural Science, New York University, 4 Washington PlaceRoom 809, New York, NY, 10003, USA.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Center for Neural Science, New York University, 4 Washington PlaceRoom 809, New York, NY, 10003, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Actor-Engel
authors.affiliation: Center for Neural Science, New York University, 4 Washington PlaceRoom 809, New York, NY, 10003, USA.
authors.forename: Ang Doma
authors.initials: AD
authors.lastname: Sherpa
authors.affiliation: Center for Neural Science, New York University, 4 Washington PlaceRoom 809, New York, NY, 10003, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Klingensmith
authors.affiliation: Center for Neural Science, New York University, 4 Washington PlaceRoom 809, New York, NY, 10003, USA.|Department of Neuroscience, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Tara G
authors.initials: TG
authors.lastname: Chowdhury
authors.affiliation: Center for Neural Science, New York University, 4 Washington PlaceRoom 809, New York, NY, 10003, USA. ca3@nyu.edu.
authors.forename: Chiye
authors.initials: C
authors.lastname: Aoki
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D006815:Hunger; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism
chemical_list: D000199:Actins; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; C053386:drebrins
keywords: Anorexia nervosa; Eating disorder; Exercise; Food restriction; Foraging; Receptor trafficking