title: Variant BDNF-Val66Met Polymorphism is Associated with Layer-Specific Alterations in GABAergic Innervation of Pyramidal Neurons, Elevated Anxiety and Reduced Vulnerability of Adolescent Male Mice to Activity-Based Anorexia.
abstract: Previously, we determined that rodents' vulnerability to food restriction (FR)-evoked wheel running during adolescence (activity-based anorexia, ABA) is associated with failures to increase GABAergic innervation of hippocampal and medial prefrontal pyramidal neurons. Since brain-derived neurotrophic factor (BDNF) promotes GABAergic synaptogenesis, we hypothesized that individual differences in this vulnerability may arise from differences in the link between BDNF bioavailability and FR-evoked wheel running. We tested this hypothesis in male BDNF-Val66Met knock-in mice (BDNFMet/Met), known for reduction in the activity-dependent BDNF secretion and elevated anxiety-like behaviors. We found that 1) in the absence of FR or a wheel (i.e., control), BDNFMet/Met mice are more anxious than wild-type (WT) littermates, 2) electron microscopically verified GABAergic innervations of pyramidal neurons of BDNFMet/Met mice are reduced at distal dendrites in hippocampal CA1 and medial prefrontal cortex, 3) following ABA, WT mice exhibit anxiety equal to those of the BDNFMet/Met mice and have lost GABAergic innervation along distal dendrites, 4) BDNFMet/Met mice show blunted ABA vulnerability, and 5) unexpectedly, GABAergic innervation is higher at somata of BDNFMet/Met mice than of WT. We conclude that lamina-specific GABAergic inhibition is important for regulating anxiety, whether arising from environmental stress, such as food deprivation, or genetically, such as BDNFMet/Met single nucleotide polymorphism.
authors: Center for Neural Science, New York University, New York, NY 10003, USA.
authors: Yi-Wen
authors: YW
authors: Chen
authors: Center for Neural Science, New York University, New York, NY 10003, USA.
authors: Olivia
authors: O
authors: Surgent
authors: Center for Neural Science, New York University, New York, NY 10003, USA.
authors: Barkha S
authors: BS
authors: Rana
authors: Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA.
authors: Francis
authors: F
authors: Lee
authors: Center for Neural Science, New York University, New York, NY 10003, USA.
authors: Chiye
authors: C
authors: Aoki
mesh_terms: D000818:Animals; D000855:Anorexia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001007:Anxiety / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D020022:Genetic Predisposition to Disease; D008297:Male; D008822:Mice, Transgenic; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D012420:Running / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005680:gamma-Aminobutyric Acid
keywords: dendritic tuft; food restriction; hippocampus; medial prefrontal; prelimbic