Brain-derived neurotrophic factor has a transsynaptic trophic effect on neural activity in an adult forebrain circuit

While hormone driven plasticity in the adult brain is well studied, the underlying cellular and molecular mechanisms are less understood. One example of this is seasonal plasticity in the avian brain, where song nuclei exhibit hormonally driven changes in response to changing photoperiod and circulating sex steroid hormones. Hormone receptor activation in song nucleus HVC elicits a robust change in activity in target nucleus RA, but the molecular signal responsible for this is unknown. This study addressed whether brain-derived neurotrophic factor (BDNF) mediates a transsynaptic effect from HVC to RA in male Gambel9s white-crowned sparrows (Zonotrichia leucophrys gambelii). In situ hybridization confirmed an increase in BDNF expression in HVC neurons of birds switched to long day photoperiod plus systemically elevated testosterone (LD+T), compared to short day (SD) conditions. BDNF expression was virtually absent in RA neurons of SD birds, increasing to barely detectable levels in a small subset of cells in LD+T birds. Infusion of BDNF protein adjacent to RA of SD birds caused an increase in spontaneous neuron firing rate. Conversely, infusion of ANA12, a specific antagonist of the tropomysin receptor kinase B (TrkB) for BDNF, prevented the increase in RA neuron firing rate in LD+T birds. These results indicate that BDNF is sufficient, and TrkB receptor activation is necessary, for the transsynaptic trophic effect exerted by HVC on RA. The dramatic change in activity of RA neurons during the breeding season provides a clear example of transsynaptic BDNF effects in the adult brain in a functionally relevant circuit. SIGNIFICANCE STATEMENT Sex steroid hormones drive changes in brain circuits in all vertebrates, both within specific neurons and on their synaptic targets. Such changes can lead to profound changes in behavior, but little is known about the precise molecular mechanisms that underlie this process. We addressed this question in a seasonally breeding songbird and found that the trophic effects of one forebrain song nucleus on its target are mediated transsynaptically by the neurotrophin BDNF. This suggests that, in addition to their role in development, neurotrophins have critical roles in adult brain plasticity.