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A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor

Nature Neuroscience volume 5, pages 539–545 (2002)Cite this article

Abstract

Cardiac function is modulated by norepinephrine release from innervating sympathetic neurons. These neurons also form excitatory connections onto cardiac myocytes in culture. Here we report that brain-derived neurotrophic factor (BDNF) altered the neurotransmitter release properties of these sympathetic neuron-myocyte connections in rodent cell culture, leading to a rapid shift from excitatory to inhibitory cholinergic transmission in response to neuronal stimulation. Fifteen minutes of BDNF perfusion was sufficient to cause this shift to inhibitory transmission, indicating that BDNF promotes preferential release of acetylcholine in response to neuronal stimulation. We found that p75−/− neurons did not release acetylcholine in response to BDNF and that neurons overexpressing p75 showed increased cholinergic transmission, indicating that the actions of BDNF are mediated through the p75 neurotrophin receptor. Our findings indicate that p75 is involved in modulating the release of distinct neurotransmitter pools, resulting in a functional switch between excitatory and inhibitory neurotransmission in individual neurons.

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Figure 1: BDNF promotes cholinergic transmission in sympathetic neuron–myocyte cocultures.
Figure 2: BDNF did not alter the postsynaptic response to neurotransmitter.
Figure 3: Acute modulation of neurotransmitter release by BDNF.
Figure 4: Trk-independent effects of BDNF.
Figure 5: Overexpression of the p75 receptor induced inhibitory neurotransmission.
Figure 6: Activation of p75 signaling pathways promotes inhibitory transmission.

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Acknowledgements

We thank G. Turrigiano, L. Griffith, E. Marder and P. Sengupta for critical reading of the manuscript, J. Hinterneder for helpful discussions, J. Mead and E. Nokes for technical assistance and G. Banker, M. Chao and B. Hempstead for help with reagents. This work was supported by grants from the US National Institutes of Health (R01 NS40168) and the Whitehall Foundation to S.J.B. The Pew Scholars Program in the Biomedical Sciences supported this work through a Pew Scholars Award to S.J.B.

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  1. Bo Yang and John D. Slonimsky: The first two authors contributed equally to this work.

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  1. Department of Biology, Volen Center for Complex Systems, 415 South St., M/S 008, Brandeis University, Waltham, 02454, Massachusetts, USA

    Bo Yang, John D. Slonimsky & Susan J. Birren

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Yang, B., Slonimsky, J. & Birren, S. A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor. Nat Neurosci 5, 539–545 (2002). https://doi.org/10.1038/nn0602-853

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