Neuron-glia communication contributes to the precise control of synaptic functions. Oligodendrocytes near synapses detect and respond to neuronal activity, but their role in synapse development and plasticity remains largely unexplored. We show that oligodendrocytes modulate neurotransmitter release at presynaptic terminals through secretion of brain derived neurotrophic factor (BDNF). Oligodendrocyte-derived BDNF functions via presynaptic tropomyosin receptor kinase B (TrkB) to ensure fast, reliable neurotransmitter release and auditory transmission in the developing brain. In auditory brainstem slices from Bdnf+/- mice, reduction in endogenous BDNF significantly decreased vesicular glutamate release by reducing the readily releasable pool of glutamate vesicles, without altering presynaptic Ca2+ channel activation or release probability. Using conditional knockout mice, cell-specific ablation of BDNF in oligodendrocytes largely recapitulated this effect, which was recovered by BDNF or TrkB agonist application. This study highlights a novel function for oligodendrocytes in synaptic transmission and their potential role in activity-dependent refinement of presynaptic properties.
- Jun Hee Kim
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal procedures were performed in accordance with the guidelines approved by the University of Texas Health Science Center, San Antonio (UTHSCSA) Institutional Animal Care and Use Committee protocols (#140045x).
- Dwight E Bergles, Johns Hopkins University School of Medicine, United States
© 2019, Jang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
The cerebrospinal fluid (CSF) contains an extracellular thread conserved in vertebrates, the Reissner fiber, which controls body axis morphogenesis in the zebrafish embryo. Yet, the signaling cascade originating from this fiber to ensure body axis straightening is not understood. Here, we explore the functional link between the Reissner fiber and undifferentiated spinal neurons contacting the CSF (CSF-cNs). First, we show that the Reissner fiber is required in vivo for the expression of urp2, a neuropeptide expressed in CSF-cNs. We show that the Reissner fiber is also required for embryonic calcium transients in these spinal neurons. Finally, we study how local adrenergic activation can substitute for the Reissner fiber-signaling pathway to CSF-cNs and rescue body axis morphogenesis. Our results show that the Reissner fiber acts on CSF-cNs and thereby contributes to establish body axis morphogenesis, and suggest it does so by controlling the availability of a chemical signal in the CSF.
Control over emotional action tendencies is essential for everyday interactions. This cognitive function fails occasionally during socially challenging situations, and systematically in social psychopathologies. We delivered dual-site phase-coupled brain stimulation to facilitate theta-gamma phase-amplitude coupling between frontal regions known to implement that form of control, while neuropsychologically healthy human male participants were challenged to control their automatic action tendencies in a social–emotional approach/avoidance-task. Participants had increased control over their emotional action tendencies, depending on the relative phase and dose of the intervention. Concurrently measured fMRI effects of task and stimulation indicated that the intervention improved control by increasing the efficacy of anterior prefrontal inhibition over the sensorimotor cortex. This enhancement of emotional action control provides causal evidence for phase-amplitude coupling mechanisms guiding action selection during emotional-action control. Generally, the finding illustrates the potential of physiologically-grounded interventions aimed at reducing neural noise in cerebral circuits where communication relies on phase-amplitude coupling.