Essential role of brain-derived neurotrophic factor in the regulation of serotonin transmission in the basolateral amygdala.
Human and animal model studies have linked brain-derived neurotrophic factor (BDNF) with the etiology of anxiety disorders. This pleiotropic neurotrophin and its receptor, TrkB, promote neuronal survival, differentiation and synaptic plasticity. Here we interrogated the role of BDNF in serotonergic neurotransmission in the basolateral amygdala (BLA), a limbic brain region associated with the neurobiology of anxiety. We found that both GABAergic and pyramidal projection neurons in the wild-type BLA contained TrkB receptors. Examination of BDNF(2L/2LCk-Cre) mutant mice with brain-selective depletion of BDNF revealed mild decreases in serotonin content in the BLA. Notably, whole cell recordings in BLA pyramidal cells uncovered significant alterations in 5-HT(2)-mediated regulation of GABAergic and glutamatergic transmission in BDNF(2L/2LCk-Cre) mutant mice that result in a hyperexcitable circuit. These changes were associated with decreased expression of 5-HT(2) receptors. Collectively, the results indicate a required role of BDNF in serotonin transmission in the BLA. Furthermore, they suggest a mechanism underlying the reported increase in anxiety-like behavior elicited by perturbed BDNF signaling.
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
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D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D012701:Serotonin