Induction of Bdnf from promoter I following electroconvulsive seizures contributes to structural plasticity in neurons of the piriform cortex.

BACKGROUND: Electroconvulsive therapy (ECT) efficacy is hypothesized to depend on induction of molecular and cellular events that trigger neuronal plasticity. Investigating how electroconvulsive seizures (ECS) impact plasticity in animal models can help inform our understanding of basic mechanisms by which ECT relieves symptoms of depression. ECS-induced plasticity is associated with differential expression of unique isoforms encoding the neurotrophin, brain-derived neurotrophic factor (BDNF). HYPOTHESIS: We hypothesized that cells expressing the Bdnf exon 1-containing isoform are important for ECS-induced structural plasticity in the piriform cortex, a highly epileptogenic region that is responsive to ECS. METHODS: We selectively labeled Bdnf exon 1-expressing neurons in mouse piriform cortex using Cre recombinase dependent on GFP technology (CRE-DOG). We then quantified changes in dendrite morphology and density of Bdnf exon 1-expressing neurons. RESULTS: Loss of promoter I-derived BDNF caused changes in spine density and morphology in Bdnf exon 1-expressing neurons following ECS. CONCLUSIONS: Promoter I-derived Bdnf is required for ECS-induced dendritic structural plasticity in Bdnf exon 1-expressing neurons.

BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior.

Brain-derived neurotrophic factor (Bdnf) transcription is controlled by several promoters, which drive expression of multiple transcripts encoding an identical protein. We previously reported that BDNF derived from promoters I and II is highly expressed in hypothalamus and is critical for regulating aggression in male mice. Here we report that BDNF loss from these promoters causes reduced sexual receptivity and impaired maternal care in female mice, which is concomitant with decreased oxytocin (Oxt) expression during development. We identify a novel link between BDNF signaling, oxytocin, and maternal behavior by demonstrating that ablation of TrkB selectively in OXT neurons partially recapitulates maternal care impairments observed in BDNF-deficient females. Using translating ribosome affinity purification and RNA-sequencing we define a molecular profile for OXT neurons and delineate how BDNF signaling impacts gene pathways critical for structural and functional plasticity. Our findings highlight BDNF as a modulator of sexually-dimorphic hypothalamic circuits that govern female-typical behaviors.

Electroconvulsive seizures influence dendritic spine morphology and BDNF expression in a neuroendocrine model of depression.

BACKGROUND: Electroconvulsive therapy (ECT) is a rapid and effective treatment for major depressive disorder. Chronic stress-induced depression causes dendrite atrophy and deficiencies in brain-derived neurotrophic factor (BDNF), which are reversed by anti-depressant drugs. Electroconvulsive seizures (ECS), an animal model of ECT, robustly increase BDNF expression and stimulate dendritic outgrowth. OBJECTIVE: The present study aims to understand cellular and molecular plasticity mechanisms contributing to the efficacy of ECS following chronic stress-induced depression. METHODS: We quantify Bdnf transcript levels and dendritic spine density and morphology on cortical pyramidal neurons in mice exposed to vehicle or corticosterone and receiving either Sham or ECS treatment. RESULTS: ECS rescues corticosterone-induced defects in spine morphology and elevates Bdnf exon 1 and exon 4-containing transcripts in cortex. CONCLUSIONS: Dendritic spine remodeling and induction of activity-induced BDNF in the cortex represent important cellular and molecular plasticity mechanisms underlying the efficacy of ECS for treatment of chronic stress-induced depression.