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 BDNF2L/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-HT2-mediated regulation of GABAergic and glutamatergic transmission in BDNF2L/2LCk-Cre mutant mice that result in a hyperexcitable circuit. These changes were associated with decreased expression of 5-HT2 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.

► We examined the role of BDNF in serotonin transmission in the basolateral amygdala. ► Inhibitory responses of BLA pyramidal neurons to serotonin are impaired in BDNF mutants. ► BDNF mutant pyramidal neurons exhibit exaggerated excitatory responses to serotonin. ► The BLA of BDNF mutant mice exhibits reduced content of 5-HT2 receptors. ► A BLA hyperexcitable circuit in BDNF mutants might underlie their increased anxiety.