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https://scholarbank.nus.edu.sg/handle/10635/144390
Title: | LOSS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) SIGNALLING IN CORTICO-LIMBIC INTERNEURONS IMPAIRS ELECTROPHYSIOLOGICAL MATURATION AND LEADS TO ANXIETY AND SOCIAL DOMINANCE IN MICE | Authors: | TAN PANG HAO SHAWN | Keywords: | BDNF, TrkB, Social Dominance, Anxiety, Interneurons, GABA | Issue Date: | 29-Jul-2016 | Citation: | TAN PANG HAO SHAWN (2016-07-29). LOSS OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) SIGNALLING IN CORTICO-LIMBIC INTERNEURONS IMPAIRS ELECTROPHYSIOLOGICAL MATURATION AND LEADS TO ANXIETY AND SOCIAL DOMINANCE IN MICE. ScholarBank@NUS Repository. | Abstract: | The tight balance between excitation and inhibition (E/I) within neocortical circuits in the mammalian brain is important for complex behavior. Many loss-of-function studies have demonstrated that brain-derived neurotrophic factor (BDNF) and its cognate receptor tropomyosin receptor kinase B (TrkB) are essential for the development of inhibitory GABAergic neurons. However, behavioral consequences of impaired BDNF/TrkB signaling in GABAergic neurons remain unclear. In this study, we generated conditional knockout mice (TrkB cKO) in which TrkB was ablated from a majority of corticolimbic GABAergic interneurons postnatally. These mice exhibited anxiety and enhanced dominance over other mice in a group-housed setting. In addition, immature fast-spiking GABAergic neurons of TrkB cKO mice resulted in an E/I imbalance in layer 5 microcircuits within the mPFC, a key region regulating social dominance. Restoring the E/I imbalance via optogenetic modulation in the mPFC of TrkB cKO mice normalized their social dominance behavior. Taken together, our results provide strong evidence for a novel role of BDNF/TrkB signaling in inhibitory synaptic modulation, anxiety and social dominance in mice. | URI: | http://scholarbank.nus.edu.sg/handle/10635/144390 |
Appears in Collections: | Ph.D Theses (Open) |
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