Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 39, Issue 1, Pages 98-106Publisher
WILEY
DOI: 10.1111/ejn.12421
Keywords
C1 neuron; channelrhodopsin 2; conditional knockout; gene disruption in mice; glutamate
Categories
Funding
- National Institutes of Health [HL28785, HL74011]
- American Heart Association [11post7170001]
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Catecholaminergic neurons of the rostral ventrolateral medulla (RVLM-CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM-CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine-beta-hydroxylase-expressing neurons in mice [D beta H-Cre/0;VGLUT2(flox/flox)) mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM-CA neurons in cKO vs. control mice (D beta H-Cre/0, using channelrhodopsin-2 (ChR2-mCherry) optogenetics. ChR2-mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (similar to 400 neurons), with identical selectivity for catecholaminergic neurons (90-99% colocalisation with tyrosine hydroxylase). RVLM-CA neurons had similar morphology and axonal projections in D beta H-Cre/0 and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2-positive RVLM-CA neurons in D beta H-Cre/0 and cKO mice. Photostimulation in conscious mice produced frequency-dependent respiratory activation in D beta H-Cre/0 mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in D beta H-Cre/0 mice only. Vagal responses were unaffected by alpha(1)-adrenoreceptor blockade. In conclusion, two responses evoked by RVLM-CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM-CA neurons are mediated by glutamate.
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